Vaccines Have Serious Side Effects

The Revised Authoritative Guide To Vaccine Legal Exemptions

Comprehensive, authoritative information about vaccine exemptions you can trust, from Alan Phillips, J.D., a leading vaccine rights attorney with years of experience helping clients throughout the U.S. legally avoid vaccines in a wide variety of vaccine-refusal settings. Critical details for parents, students, immigrants, healthcare employees, military personnel and contractors, agencies, attorneys and clientsvirtually anyone concerned with legally avoiding vaccines in the United States. This Guide provides and explains: Important background information about the legal system; How state and federal statutes, regulations, constitutions and legal precedent interact to define the boundaries of your legal exemption rights; How to deal with local authorities and to avoid mistakes that cost others their exemption; Where legal technicalities and practical reality differand what to do about it; Read more here...

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Lessons from Successful Vaccines against Other Pathogens

Studies of the immune correlates of protection associated with existing vaccines reveal that Ab responses play a dominant role. Only BCG vaccination against Mycobacterium tuberculosis induces immunity in which Abs appear to have no role. Since CTL responses are likely to be required for an effective HIV-1 vaccine, traditional vaccine technologies are likely to be suboptimal, or counter-indicated due to safety concerns. Many existing vaccines are based on live-attenuated microorganisms. Such vaccines have potential hazards such as transmission to unvaccinated persons and the risk of reversion to pathogenicity, both of which have been observed with the Sabin oral polio vaccine. Killed microorganism vaccines do not have these drawbacks. However, they are occasionally associated with disease when the inactivation process is incomplete, and are inefficient at inducing CTL responses. Due to these factors, neither the live-attenuated nor killed vaccine approaches appear to be suitable for...

Clinical Trials of HIV1 Vaccine Candidates

In 2003, VaxGen announced that phase III efficacy trials of its gp120-based AIDSVAX candidate, aimed at inducing nAb responses, had failed to protect volunteers. The inadequacy of AIDSVAX and emergence of data suggesting CTLs play the major role in the control of HIV-1 heralded a paradigm shift away from the induction of nAb responses toward inducing CTL responses. Reflecting this, most of the vaccines currently on trial are based on strategies that have, as their primary or sole aim, the induction of CTL and T-helper responses against HIV-1. Thus, the main hypothesis currently being tested in clinical trials is that CTL responses can be induced safely in humans and will impact upon viral load and disease progression as they have done in primate models of simian-human immunodeficiency virus (SHIV) infection. In 2007, the phase IIb trials of the MRKAd5 trivalent vaccine developed by Merck & Co, which aimed to give 'proof of concept' for the CTL-based approach in man were...

Inducing Cell Mediated Immunity by Vaccination

In macaque models, vaccination with DNA plasmids or recombinant viruses bearing SIV SHIV antigenic inserts leads to significant attenuation of viremia after subsequent infection with the highly pathogenic X4-tropic hybrid isolate SHIV89.6P. Although they do not afford sterilizing immunity under any regimen tested thus far, such vaccines enable long-term suppression of viremia and prevent disease progression. Nonetheless, eventual escape of the challenge virus from CTL control after acquisition of single amino acid mutations in critical immunodominant epitopes is sometimes observed. This results in rapid rebound of viremia and normal disease progression, and underlies the necessity of targeting the most conserved epitopes critical for viral fitness, as well as targeting multiple epitopes if 'breakthrough' replication is to be avoided. A critical caveat of the work in macaques with the frequently used SHIV-89.6P is that this virus appears to be unusually sensitive to vaccine-induced...

Diagnosis Treatment And Vaccine

Two plague vaccines have been approved for use in humans. One is a formaldehyde-killed, whole-cell vaccine first used in 1942, and the other is a live vaccine used in the former Soviet Union since 1939. A new subunit vaccine that uses the bacterial capsular antigens F1 and V for immunization is under development.

Immunology and Vaccination

Particles of HPV-16 and HPV-18 consisting only of L1 protein have been developed as vaccines by Merck and GlaxoSmithKline, the product of the former company also including HPV-6 and HPV-11 capsids. The vaccines became available in 2006 07, and have been cleared by the Food and Drug Administration of the United States for prophylactic vaccination of women aged 9-26. Vaccination during extensive clinical studies efficiently protected PV-uninfected women against de novo PV infections over periods exceeding 5 years. The vaccinations led to the stimulation of humoral immune responses by more than an order of magnitude beyond levels found in natural infections. The success of this approach is apparently based on anti-PV immune globulin concentrations in cervical mucus

Prevention and Vaccine

No vaccine is yet available and the only effective prevention at present is education about the ways of transmission, systematic testing of blood donors and the use of condoms. However, an important reduction of transmission from mother to child has been achieved by treatment with AZT of the mother at the end of pregnancy and at the time of delivery and of the newborn in the first weeks of life. A lighter regimen also seems to be effective and applicable to populations of developing countries. A complete control of the AIDS epidemic cannot be achieved without the availability of a protective vaccine. Although the use of whole virus or whole surface glycoproteins has been disappointing, there are new promising approaches based on the use of DNA, mucosal adjuvants and live vectors, internal and regulatory proteins, and conserved parts of the surface glycoproteins. The efficacy trials of candidate vaccine in large populations will raise important logistic and ethical issues difficult to...

Vaccines And Diagnosis

Kinetoplastid CATB and CATL enzymes are potential candidates for vaccine development, either by preventing infection or decreasing pathology.4 Immunization of cattle with recombinant TcoCATL did not prevent infection with T. congolense but the vaccinated cattle maintained or gained weight and had less-pronounced anaemia during the chronic phase of the disease.76 Injection of mice with TcrCATL DNA stimulated cytotoxic T-lymphocytes that recognized and killed T. cruzi-infected cells.77 In other experiments, immunization of mice with recombinant TcrCATL conferred protection against experimental infection.78 Likewise, immunization with DNA plasmids encoding Leishmania CATLs resulted in protective immunity in murine models of cutaneous and visceral leishmaniasis.79-81 Finally, vaccination of BALB c mice with CATB was partially protective against Leishmania infantum infections.82

Fear of Autoimmunity Can Hold Up Vaccine Development

On a more negative note, a mistaken belief in autoimmunity can hold up vaccine development, as Kierszenbaum cogently argues for Chagas' disease 63 . This is a disease where a vaccine is much needed high disease prevalence in particular areas, lack of effective symptomatic treatment and lack of effective anti-parasite measures. Meningococcus B is another instance. Conjugate vaccine against Meningococcus C composed of capsular polysaccharide conjugated to a protein carrier is effective and now widely used. A similar vaccine against Men B has not been developed because of the danger presented by expression of a cross-reactive polysaccharide in neural tissue (Table 5). Instead, several serogroup B vaccines based on outer membrane vesicles have been shown to be immunogenic and reasonably effective in adults and older children, but the protection offered by them is chiefly strain-specific. Table 5 Where threat of autoimmunity impedes vaccine development Table 5 Where threat of autoimmunity...

Recombinant Avipoxvirus Vaccines

Recombinant FWPV as a Vaccine Vector in Poultry Shortly after the development of methods for isolating recombinant VACV in the early 1980s, FWPV was developed as an equivalent recombinant vector for use in poultry. Several commercial vaccine and laboratory attenuated strains were used as vectors against a number of important poultry pathogens, especially avian influenza virus, Newcastle disease virus, infectious bronchitis virus, avian hem-orrhagic enteritis virus, Marek's disease virus, turkey rhinotracheitis virus, REV, and infectious bursal disease virus, as well as Mycoplasma gallisepticum. Commercial recombinant FWPV vaccines against Newcastle disease virus and avian influenza virus have been licensed for commercial use in the USA. Those against avian influenza have also been licensed for use in Mexico indeed, between 1997 and 2003, approximately 459 million doses of a recombinant fowlpox-H5 vaccine were used in Mexico as part of a program to control H5N2. The same recombinant...

Vaccines and Chemotherapy

Very successful live attenuated vaccines are in general use against certain 'respiratory' viruses like measles, mumps and rubella, which, though naturally trans mitted via the respiratory route, are absolutely dependent upon viremic spread to their target organs elsewhere in the body. In contrast, it is a much more challenging assignment to develop effective vaccines against viruses whose pathogenicity is essentially confined to the respiratory tract. The major reasons for this are that (1) secretory IgA memory is relatively short-lived, and (2) numerous antigenically distinct strains or serotypes are capable of causing the same clinical syndrome. Thus, a common cold vaccine might need to contain dozens of different serotypes of rhinoviruses ( coronaviruses). An inactivated vaccine is used to protect the aged and other risk groups against the currently prevalent strains of influenza, but its composition must be updated regularly to keep abreast of antigenic drift and shift and, even...

Immunization Vaccination

Although viral illnesses occur with high frequency and often devastating effect in transplant recipients, vaccination presently has only a limited role in disease prevention. There are a number of reasons why this should be so. Transplant patients are heavily immunosuppressed, and make poor antibody or T cell responses to killed subunit vaccines. Administration of live attenuated vaccines, which are potentially more immunogenic, is fraught with peril, since the immune response may be so feeble that even attenuated viruses may produce fatal disease. Finally, effective vaccines to herpes viruses in humans are simply not available. Since it is precisely that virus group which is responsible for most viral-related morbidity and mortality after transplantation, vaccination can at best have a limited impact on outcome. For example, several studies have examined the effect of attenuated Towne strain in renal transplant recipients. Unfortunately, the vaccine induces minimal specific cytotoxic...

Factors Affecting the Feasibility of Vaccine Development

Table 3 lists some of the factors which make it more straightforward to develop a vaccine against a virus, and these can be contrasted with those which tend to increase the difficulty. It can be readily seen that most of the latter points apply to HIV. Ada GL and McElrath MJ (1996) Perspective. HIV-1 vaccine-induced cytotoxic T cell responses potential role in vaccine efficacy. AIDS Res. Hum. Retrov. 13 243. Ada G and Ramsay A (1997) Vaccines, Vaccination and the Immune Response. Philadelphia Lippincott Raven.

Advantages of DNA Vaccines

DNA vaccines represent a new approach to immunization, in that an individual is directly inoculated (injected) with DNA that genetically encodes one or more of the antigens associated with the infectious agent. In effect, the recipient of a DNA vaccine produces the immunizing protein (antigen) within his own cells as a result of the immunization process. This revolutionary approach to vaccination offers many advantages over conventional vaccines. A major advantage is that DNA vaccination stimulates both the antibody and cell-mediated components of the immune system, whereas conventional protein vaccines usually stimulate only the antibody response. Furthermore, DNA vaccines are simpler to produce and store than conventional vaccines, and are therefore less expensive. Preliminary studies to date indicate that DNA vaccines appear to be very safe and to produce no side effects.

DNA Vaccination Techniques

DNA vaccination involves immunization with a circular piece of DNA, known as a plasmid, that contains the gene (or genes) that code for an In many respects, this process is reminiscent of what occurs during a viral infection, when viral proteins are expressed within host cells. Thus, a DNA vaccine is somewhat like a very simple, nonreplicating virus. However, plasmid DNA vaccines do not replicate within the host, and therefore do not infect neighboring cells, as occurs during a viral infection. This innovation in vaccination strategy was discovered some years ago, but the active development of this technology only began after Stephen Johnston's group at the University of Texas Southwestern Medical Center demonstrated that plasmid DNA can induce the formation of antibodies against an encoded protein in 1992. Johnston's group was able to show that when mice are innoculated with plasmid DNA encoding human growth hormone, the mice produce antibodies against the hormone. There are two...

Conclusion Genomics And Vaccination

Despite the advances associated with molecular techniques, meningococcal disease remains a globally significant health problem, and the prospect of comprehensive vaccination remains elusive. Whereas vaccines based on the capsular polysaccharide are either licensed or under development against meningococci associated with serogroups A, C, and Y, as well as W-135, attempts to develop a polysaccharide-based serogroup B vaccine have proven unsuccessful. This fact is especially relevant as much of the meningococcal disease in Europe and North America is caused by meningococci associated with the serogroup B capsule. A number of alternative approaches to the development of serogroup B meningo-coccal vaccines are currently in development, 14 and these are summarized in Table 1. The recent completion of three meningococcal genomes (http www.sanger. Projects N_menigitidis ) Refs. 23,24 has revolutionized the process of vaccine development and the application of genomic approaches such as...

Vaccine Clinical Trials

Similar to clinical development of drug products, there are four phases of clinical trials in vaccine development. Phase I trials are referred to early studies with human subjects. The purpose of phase I trials is to explore the safety and immunogenicity of multiple dose levels of the vaccine under investigation. Phase I trials are usually of a small scale. Phase II trials are to assess the safety, immunogenicity, early efficacy of selected doses of the vaccine, and generate hypotheses for later testing. Phase III trials, which are usually large in scale, are to confirm the efficacy of the vaccine in the target population and or proving consistency of manufacturing processes. Phase IV trials are usually conducted for collecting additional information regarding long-term safety, immunogenicity, or efficacy of the vaccine to fulfill with regulatory requirement and or marketing objectives after regulatory approval of the vaccine. In this section, we provide some design considerations,...

Two Main Requirements of a Vaccine

The safety of a candidate vaccine has become of prime importance. Most of the vaccines listed in Table 1 are very safe, but two in particular are less so. During the eradication campaign, most smallpox vaccines (vaccinia virus) had a level of side effects which made them unacceptable for current use. Safer preparations have since been made by the deletion of specific DNA sequences. Type 3 poliovirus in OPV can revert to virulence, and poliomyelitis occurs at the rate of about 3 X 106 doses of vaccine in recipients or their close contacts. Attenuated live vaccines may pose a risk to immunodeficient or -compromised people, but at least in the case of measles virus, even this is a very low risk. The second requirement is efficacy, which is assessed as the ability to protect recipients from disease after a subsequent exposure to the wild-type infectious agent. Vaccine efficacy depends almost entirely on the nature and persistence of the induced immune response. Vaccines are usually given...


First attempts to vaccinate against swine fever date back to the beginning of the last century, when pigs were infected with live virus and simultaneously treated with serum from immune pigs. This high-risk practice was replaced in the 1940s by the use of inactivated and modified live vaccines (MLVs).While the inactivated vaccines proved rather inefficient, MLV turned out to be highly efficacious and safe in pigs of any age, for example, the GPE- and the lapinized Chinese strain (C-strain) of CSFV. The latter is probably the most popular MLV against CSF. When properly used, MLVs are powerful tools for prophylactic protection of domestic pigs against CSF. In countries still struggling with endemic CSF, vaccines are being used in order to limit economical damage. The systematic use of these vaccines often was and is the first step in the eradication of CSF. In countries that have eradicated the infection, prophylactic vaccination is usually banned, mainly because animals vaccinated with...

DNA Vaccination

Great excitement has greeted the possibility of using purified DNA encoding viral proteins to vaccinate against viral infections. The mechanism of presentation of DNA-encoded antigens to the immune system remains to be established but, in principle, DNA vaccination is similar to vaccination with infectious virus. Thus, the synthesis of viral proteins by antigen-presenting cells transfected by the vaccinating DNA will provide peptides to class I molecules, and viral proteins released from transfected cells should be processed and presented with class II molecules by professional antigen-presenting cells. Viral proteins released from transfected cells also stimulate B cells. Indeed, it has been found that neutralizing antibodies, TCD4+ and TCD8+ responses are induced following immunization in animals with DNA encoding influenza virus proteins. The immune response is, however, less potent than that obtained following immunization with live attenuated influenza virus, and it remains to be...


Two types of vaccines have been successfully tested in the SRV AIDS model. The first used a killed-virus formulation. The virus was inactivated with formalin and injected intramuscularly to induce antibody. The SRV challenge virus used to test the efficacy of the vaccine was prepared in isogenic rhesus monkey kidney cells, therefore ruling out induction of anticellular antibody as a protective mechanism. Protection was associated with neutralizing antibody. This was the first vaccine shown to be effective against a primate retrovirus. The second vaccine used a recombinant vaccinia virus vector. The vaccinia virus vector expressed the envelope proteins (gp70 and gp20) of SRV-1 and MPMV. Upon challenge with live SRV-1 by the intravenous route, both MPMV- and SRV-1-immunized animals were protected. The vaccine therefore conferred cross-protection for SRV types 1 and MPMV, demonstrating in vivo their close relationship. The neutralizing antibody did not cross-react with the more distant...

Classic Vaccines

One of the greatest achievements in the history of medicine has been the development of vaccination. The use of vaccines has saved more lives than all other medical procedures combined, and represents one of the highest points in civilization's technical accomplishments. Vaccines are used to mobilize the immune system to prevent or combat infectious disease caused by exposure to viruses, bacteria, or parasites. A vaccine works by mimicking an infectious agent and inducing a protective immune response in the host, without actually causing the disease. Successful vaccination provides protection for individuals by making them immune to the disease, and it protects whole populations by hindering the spread of the infectious agent. Historically, vaccines have consisted of formulations using live, noninfectious (attenuated) microbes that resemble the original pathogen whole organisms that have been killed or purified by-products of the infectious agent. More recently, some vaccines have...

Stephen P Robinson md phd Andrew J Stagg phd

Meningococcal Vaccines Methods and Protocols, edited by Andrew J. Pollard and Martin C. J. Maiden, 2001 Protocols, edited by Katherine B. Bushby and Louise Anderson, 2001 42. Vaccine Adjuvants Preparation Methods and Research Protocols, edited by Derek T. O'Hagan, 2000

Prevention and Therapy

In the USA, orally administrate, live, enteric-coated vaccines against HAdV-4, HAdV-7, and HAdV-21 were used in military units for a couple of decades. After the cessation of vaccine production in 1996, the impact of adenovirus infection among military recruits increased, and re-emergence of HAdV-7 and especially HAdV-4 has been verified. Since 1999, 12 of all recruits were affected by adenovirus disease. Efforts to resume vaccination are in progress. In the veterinary practice, dog vaccination schedules all over the world invariably include a live or killed CAdV-1 component against dog hepatitis. Inactivated vaccine for horses against equine adenoviruses has been prepared in Australia. In farm animals, inactivated bivalent vaccines (containing one mastadenovirus and one atadenovirus) have been in use in several countries for controlling enzootic calf pneumonia or pneumo-enteritis. In poultry practice, commercially available or experimental vaccines for the prevention of EDS or turkey...

Pathogenicity and Clinical Features of Infection

Avirulent and virulent strains of EAV and PRRSV have been isolated. Attenuated vaccine strains of EAV and PRRSV have been selected and used as vaccines. Although these vaccines induce immunity against disease, immunized animals are not protected from reinfection. Horses infected with the virulent Bucyrus strain of EAV develop a high fever, lymphopenia and severe disease symptoms. LDV-C differs from other LDV isolates in its ability to infect ventral motor neurons in immunosuppressed C58 and AKR mice and induce poliomyelitis. Isolates of SHFV that induce persistent, asymptomatic infections and ones that cause acute, asymptomatic infections in patas monkeys have been reported. All SHFV isolates cause fatal hemorrhagic fever in macaque monkeys.

Prevention and Control

Killed and attenuated live vaccines for EAV and PRRSV are commercially available. The live vaccines are more effective and induce a longer-lasting immunity than the killed vaccines. Although animals immunized with the live vaccines are protected from disease, they are not protected from reinfection and can spread virus. Current serological assays can not distinguish field strains from vaccine strains.

Future Perspectives

Arteriviruses have so far been isolated from mice (LDV), horses (EAV), pigs (PRRSV) and monkeys (SHFV). It seems likely that other host species, including humans, may harbor additional members of this virus family. Such viruses will be especially difficult to find in natural hosts that develop asymptomatic infections. Because of the inapparent and persistent nature of infections caused by LDV, PRRSV, SHFV and EAV it is important to develop rapid and reliable diagnostic tests for these viruses to easily identify infected animals. The availability of complete genomic sequences for EAV, PRRSV, SHFV and LDV should facilitate the development of new diagnostic assays and vaccines and may also provide the means for detecting additional arteriviruses. See also Immune response Cell mediated immune response, General features Vaccines and immune response.

Transmission and Tissue TTopism

Transmission of virus is principally vertical by infection of the offspring through virus secreted into the egg. Indeed, high titers of ALV are often detectable in commercial hen's eggs. Horizontal spread of virus is naturally much more rare, requiring close contact, but virus can be readily spread from infected birds via contaminated needles during vaccination or through vaccines prepared from infected eggs or cell cultures.

Fear of the Microorganisms and Response

How have humans responded to the threat posed by microorganisms Penicillin, latex condoms, streptomycin, chloroquine, pyrimethamine, and vaccines are some of the effective prophylactics or treatments developed as an answer to some of the diseases. The combinations of widespread immunization campaigns and successful strategies and products developed by the scientific community have countered the threats posed to both developed and developing nations. While recent scientific achievements in infection control measures, especially antibiotics or antimicrobials, yield measurable successes, the misuse and underuse of them have diminished possible benefits in the developing countries. According to the World Health Organization (WHO), more than 10 million children die each year before their fifth birthday, most from preventable causes, and almost all such children from poor countries. Though the causes of death differ substantially from one country to another, diarrhea, pneumonia, and malaria...

Discharge And Home Healthcare Guidelines

Allergic purpura occurs in response to agents such as bacteria, drugs, food, or bee stings. The allergic reaction, probably an autoimmune response directed against the vessel walls, may be triggered by a bacterial infection. Most patients have experienced an upper respiratory infection, particularly a streptococcal infection, 1 to 3 weeks prior to the development of allergic purpura. Experts suggest that other causes, such as allergic reactions to drugs and vaccines, insect bites, and foods (wheat, eggs, chocolate, milk) may lead to the condition.

Optimizing Antigens to Induce Abs with Antiviral Activity

The problem of inducing Abs of the correct specificities that will have protective roles in vivo has proved difficult to solve. It is clear from clinical trials conducted thus far that vaccination with native gp120, gp160, gp41, or Env peptides fails to induce nAbs against more than a handful of isolates. Therefore, improved strategies that aim to circumvent the immuno-evasive properties of Env are being developed. The use of consensus sequence Env reduces the antigenic distance between the vaccine strain and isolates that will be encountered in the field. So far, consensus sequence Env has induced nAb responses of equal or slightly better breadth compared to naturally occurring strains, suggesting at best, only an incremental improvement. Attempts to recapitulate the native structure of the fusogenic virion-associated Env trimeric spike have also produced incremental improvements when compared with monomeric gp120. Since Gag drives the self-assembly of the virion, virus-like...

Selecting the Best Target Antigens

The obvious advantage of CTL-based vaccines over those that aim to induce nAbs is that all HIV-1 proteins are targets for cellular immunity and some of these are considerably less tolerant of mutation than Env. CTLs escape mutations with a high cost to viral fitness and revert after transmission to a new host where the epitope is not targeted. Conversely, CTL epitopes restricted by common HLA class I alleles that are not critical to viral fitness will drive the accumulation of escape mutants in a population, since the chance of mutant virus being transmitted to individuals with the same restricting HLA class I allele is high. This necessitates the rational design of vaccine immunogens to provide epitopes for the less common HLA alleles that may prove more effective at combating HIV-1 and delineating which epitopes of a mutant virus may still be presented by the common HLA alleles. Targeting early antigens such as Tat, Rev, and Nef allows CTLs the greatest amount of time to act on an...

Gender Ethnicracial And Life Span Considerations

Anaphylactic shock can occur at any age and in both men and women, but women seem a little more susceptible than men. Individuals with food allergies (particularly shellfish, peanuts, and tree nuts) and asthma may be at increased risk for having a life-threatening anaphylactic reaction. People at the ends of the lifespan are most at risk. To prevent infants and children from experiencing severe allergic reactions, pediatricians carefully plan vaccines and diet to limit the risk of allergic reaction until a child's immune system is more mature. Severe food allergy is more common in children than in adults, but diagnostic contrast, insect stings, and anesthetics are more common in adults than in children. Teenagers with food allergies and asthma may be at high risk for an allergic reaction because they are more likely to eat outside the home and less likely to carry their medications. Older people also have a great risk of anaphylaxis, and their risk of death is high owing to the...

Life Span and the Aging Process

This increase was likely due to several factors, but perhaps the most important was the improvement of sanitation, hygiene, and public health from 1900 to 1998. These improvements included purification of drinking water, treatment of wastewater, widespread vaccination, and improved access to health care. However, even as these sanitary measures were adopted, other elements of modern life emerged as strong influences on life span, such as diet, exercise, and socioeconomic status. Studies have shown that individuals who exercise regularly, eat a diet lower in saturated fats, and avoid unnecessary risk-taking live longer. This may be because such a lifestyle reduces the risk of developing cardiovascular disease and cancer, the top causes of death in developed countries.

Bromoviruses Bromoviridae

To investigations of the role of co-infections in development of disease and of host genetic factors affecting infection and development of disease. Approaches to vaccination can be tested. The role of the cell-mediated immune response in protection from infection or from development of tumors remains a challenging area for investigation.

Release of First MLV Followed by Reports of pvMD

Because cytopathic strains could be more easily detected, quantitated, and studied in tissue culture than noncyto-pathic strains, the discovery of cytopathic BVDV was a boon to the study of BVDV. In 1964, the first cytopathic BVDV strain discovered (Oregon C24 V) was incorporated into a modified live multivalent vaccine. Soon it was reported that subsequent to use of this vaccine a minority of animals became sick with MD-like symptoms and died. These cases were referred to as postvaccinal MD (pvMD). Further investigation revealed that the vaccinated animals that succumbed to pvMD responded with serum antibodies to the other components of the vaccine but did not respond to the BVDV component. This suggested that the susceptibility to pvMD might be correlated with failure of the immune system to recognize BVDV. Questions raised by pvMD lead to the elucidation of the etiology of MD.

Segregation of BVDV into Two Genotypes

Studies done in the late 1980s and early 1990s, comparing vaccination cross-protection and monoclonal antibody binding, revealed antigenic variability among BVDV strains. While these studies indicated that there was considerable variation among BVDV strains, no standard means of grouping viruses based on these variations was generated. Meanwhile, based on hybridization analysis and sequence comparison, several groups evaluated the 5' untranslated region (UTR) as a target for polymerase chain reaction (PCR) tests designed to detect the wide range of BVDV strains or to differentiate BVDV strains from other pestiviruses. pathogenesis of BVD-MD. However, the recognition of hemorrhagic syndrome in the late 1980s and early 1990s brought the concept of severe acute BVD once more to the forefront. Case records of cattle admitted to the Cornell College of Veterinary Medicine for the years 1977-87 revealed that 10 of clinically acute BVD infections in adult cattle were associated with...

Emergence of BVDV Reduction Eradication Programs

In the decades after the first description of BVD and the discovery of its causative agent, systematic reduction eradication programs were not considered. This was partially due to an underestimation of the economic impact of BVDV infections and the lack of suitable diagnostics. In the mid-1990s studies began to appear showing the sizable economic impact BVDV infections have on beef and dairy industries worldwide. Initially, veterinarians and producers assumed that vaccination alone could substantially reduce the incidence of BVDV infections. However, by the late 1990s it became apparent that four decades of vaccination had not reduced the incidence of BVDV. At this time, better diagnostics, particularly for the detection of PI animals, began to be developed. Concurrently, in the Scandinavian countries, programs designed around a strict testing and removal program for PI accompanied by movement restrictions for infected herds resulted in near eradication of BVDV in those countries by...

Differences between BVDV1 and BVDV2

BVDV1 and BVDV2 strains are antigenically distinct as demonstrated by serum neutralization using polyclonal sera and monoclonal antibody binding. The practical significance of antigenic differences is indicated by the birth of BVDV2 PI animals to dams that had been vaccinated against BVDV1 strains. While modified live BVDV1 vaccines may induce antibodies against BVDV2 strains, the titers average one log less than titers against heterologous BVDV1 strains. These observations have lead to the inclusion of both BVDV species in BVDV vaccines.

Detection and Control

BVDV diagnostics have focused on the detection of PI animals. Virus isolation on cultured bovine cells remains the gold standard. However, due to ease and lower expense, antigen detection by either immuno-histochemistry or antigen capture ELISA or nucleic acid detection by RT-PCR are gaining favor. Both killed and modified live vaccines are available for the prevention of BVD. Control by vaccination alone is compromised by the heterogeneity observed among BVDV strains, lack of complete fetal protection afforded by vaccination, and the failure to remove PI animals from cattle populations.

Host Range and Virus Propagation

Isolates of capripoxvirus derived from cattle have been adapted to grow on the chorioallantoic membrane of embryonated hens' eggs, although attempts to grow isolates from sheep and goats in eggs have been unsuccessful. Vaccine strains of capripoxvirus have been adapted to grow on Vero cells. Capripoxvirus will not grow in any laboratory animals.

Molecular Characterization Of B Pertussis And B Parapertussis

Molecular characterization and typing of B. pertussis and B. parapertussis are used to obtain information on the changes in the phenotype and genotype of circulating isolates and in epidemiological studies. When polymorphisms in a number of B. pertussis genes encoding for virulence factors and surface-associated proteins as well as in housekeeping genes were studied, B. pertussis proved to be a rather conserved bacterium. Polymorphisms in recent isolates are restricted to genes encoding tracheal colonization factor, pertactin (Prn), and the S1 subunit (ptxSl) of PT. 9,14 Pertussis toxin and pertactin are important virulence factors and protective antigens. Pertussis toxin is a component of all and Prn of many new acellular vaccines and, thus, the degree of allelic variation in genes encoding these proteins has been studied intensively in many countries. The majority of the currently circulating isolates express PT and Prn types that are different from types included in the vaccines...

Molecular Testing In The Epidemiological Typing Of B Pertussis Isolates

The finding that the currently circulating strains harbor ptxS1 and prn alleles different from those in strains used for vaccine production emphasizes the importance of monitoring the molecular evolution and antigenic variation of clinical isolates. In epidemiological studies, PFGE is used for the determination of the overall genotype of the isolates. Serotyping and the determination of ptxS1 and prn alleles provide information about the expression and polymorphism of these virulence factors at a singlegene level. To date, the only way to determine alleles encoding for important antigens has been PCR-based sequencing, a relatively time-consuming and expensive method. Thus, new simple methods suitable for large-scale screening of isolates are needed. Recently, real-time PCR using fluorescent-labeled hybridization probes has been applied to the determination of prn and ptxS1 alleles of B. pertussis 24,25 These assays proved a good alternative to sequencing as they correctly identified...

Serologic Relationships and Variability

Polyclonal sera fail to distinguish in the virus neutralization test between any of the isolates of capripoxvirus so far examined. Sheep, goats, or cattle that have been infected with any ofthe isolates are totally resistant to challenge with any ofthe other isolates. On this basis, it has been possible to use the same vaccine strain to protect all three species. No monoclonal antibodies are as yet available against capripoxvirus, but it can be expected that differences will emerge between strains using these reagents.

Circoviruses and Gyroviruses Induce Diseases

PCV1 and PCV2 seem to be restricted to pigs. PCV2 is the etiological agent of a new disease in swine, the so-called post-weaning multisystemic wasting syndrome (PMWS), and may be involved in several other porcine circoviral diseases (PCVDs) like porcine dermatitis and nephropathy syndrome (PDNS) or porcine respiratory disease complex. PMWS was first recognized in Canada in 1991. Since then it has been described as a major economic concern in virtually all pig-producing areas of the world. PMWS primarily occurs in pigs between 60 and 80 days old. Maternal antibodies confer titer-dependent protection against PCV2 infection - higher titers are generally protective, but low titers are not. PMWS is characterized by wasting, respiratory signs, enlargement of superficial inguinal lymph nodes, diarrhea, paleness of the skin or icterus, but the clinical signs are often variable. The most consistent feature of PMWS is a generalized depletion of lymphocytes. Secondary infections with...

Transmission and Host Range

Experimental transmission of CSFV to goats, sheep, cattle, peccaries (Tayassu tajacu), and rabbits was successful, while other vertebrates, for example, racoons, mice, and pigeons did not support the propagation of the virus. Of all species, the rabbit has been of major importance because it was, and in some countries still is, used for the attenuation of CSFV and for large-scale production of live vaccine virus.

Prevention and Control of Coronavirus Diseases

Because of the economic importance of coronavirus diseases of domestic animals, modified live vaccines against IBV, TGEV, BCV, CCV and FIPV have been developed. However, they do not provide solid protection from infection with wild-type coronaviruses. Other approaches to protection or control of coronavirus diseases include use of recombinant S proteins, synthetic peptides that mimic neutralization epitopes, passive immunization with antibody against S glycoproteins, and treatment with interferon a or monoclonal antireceptor antibody. Improvement of vaccines will require understanding of coronavirus virulence factors, strain variation and mechanisms of immunopathology.

Regulatory Suppression of Autoimmune T Cells But How Do Suppressor T Cells Know

AnothertypeofregulatoryTcells were detected soon afterthe first isolation of MBP specific encephalitogenic T cell lines, when Ben-Nun et al. observed that transfer of the cell not only mediated EAE, but in addition protected animals that had survived disease from renewed attempts to transfer EAE with the same cell line (Ben-Nun et al. 1981). This protection effect was not only seen after transfer of viable T cells, but even after transfer of inactivated T cells. The latter failed to transfer disease, but still procured protection, a phenomenon that laid the basis for T cell vaccination strategies. Later work showed that protection was mediated mainly by CD8 T cells, which recognized clone-specific structures on the surface of the vaccinating CD4 T cells (Lider et al. 1988 Sun et al. 1988). The importance of CD8 T cells as counter-regulatory cells has been stressed by several groups who depleted CD8 T cell from rodents in vivo, and by such treatment ablated protection against repeated...

Properties of the Virion

Pooled human y globulin, which has a respectable titer of antibodies to CMV, has been in use as a prophylactic therapy in transplant settings to reduce the incidence of CMV disease alone and in combination with antiviral compounds. Monoclonal antibodies that have a strong neutralizing capability have been tested but have thus far failed to show the benefit ascribed to human y globulin. Vaccines for CMV were initially developed in the 1970s, and one, Towne 125, has undergone almost continuous evaluation since its initial characterization. This vaccine induces cell-mediated and humoral immunity to CMV, and, when evaluated in a solid organ transplant setting, was attributed with reduction in disease severity. Due to the fact that immunity induced by Towne 125 is not as strong as that induced by natural infection, recombinant chimeric viruses that combine segments of the Towne vaccine genome and a low passage strain, Toledo, have been made to test for immuno-genicity. Vaccines consisting...

Dl Particles in Natural Infections

DI RNAs are identified in stool and blood samples of humans suffering from hepatitis A virus, an infection known to be rather moderate and prolonged. DI particles are identified in measles virus-attenuated vaccine preparations which have been, and are being, widely and successfully used (raising the question of DI particle participation in vaccine attenuation). Measles viruses defective in viral assembly are currently found associated with human subacute sclerosing panencephalitis (SSPE). The brain cells of SSPE patients were, moreover, shown to harbor many species of measles virus copy-back DI RNAs. Direct amplification of a portion of the HIV tat gene from infected patients demonstrates that about a third of the sequences correspond to defective

Tick Borne Flaviviruses

Incidence occurring in Austria where there is widespread use of vaccine. Humans acquire TBEV infection from tick bite, or from the ingestion of unpasteurized infected milk of sheep, goats, and cows. Less than 5 of humans develop symptomatic infection, but high death rates occur in patients who develop nervous disease. There may be neurological sequelae in those who recover, and a few patients develop chronic infections. A fatal hemorrhagic syndrome of humans has been described in the Novosibirsk region of Siberia in association with TBEV-FE infection. Recently, fatal TBEV-Eu infection was reported in captive monkeys in Germany which were inadvertently exposed to ticks.

Enteritis Necroticans Disease Summary

Enteritis necroticans (also known as necrotizing enteritis, Darmbrand, or Pigbel) caused by C. perfringens type C isolates is a rare but potentially lethal enteric disease of humans. This illness was first recognized after World War II in Darmbrand, Germany and later in Papua New Guinea. 20 The p -toxin produced by type C isolates is considered as the primary virulence factor based on the relative efficacy of a p-toxoid vaccine. 20 Although the incidence of enteritis necroticans is low, risk factors include reduced intestinal motility and or low intestinal trypsin levels (the p-toxin is trypsin-sensitive) because of preexisting conditions created by a protein-poor diet, helminthic coinfection, and or pancreatic disease. 20 The offending type C isolates can be introduced exo-genously by ingestion of undercooked meat products (commonly pork).

Geographic Distribution

FMD occurs widely and is endemic in many countries, especially in tropical regions (Figures 4 and 5). North America, Australia, New Zealand, and Japan are free of the disease and maintain this status by rigorous application of import controls and quarantine. Mass vaccination campaigns have virtually eliminated the virus from some areas, for example, Europe, but have been less effective in others, largely due to logistical problems of vaccine distribution and the techniques of animal husbandry employed. The global distribution of the serotypes is shown in Figures 4 and 5.

Serological Relationships and Variability

For epidemiological studies and vaccine strain selection, the serological relationships between field virus isolates or laboratory strains are expressed as r values, that is, the ratio of the neutralizing titers of immune sera against heterolo-gous and homologous viruses. The serological relationships between virus isolates are frequently nonreciprocal, showing that closely related viruses may induce broadly cross-reactive or narrowly specific immune responses. Complement fixation assay and enzyme-linked immunosorbent assay (ELISA) using polyclonal sera or monoclonal antibodies are also used for epidemiological studies.

Insectderived Tools Used For Biotechnological Research

Production of large amounts of a particular protein is extremely valuable for both research and industrial purposes. Baculoviruses, which are double-stranded DNA viruses that infect mainly insects, have been developed as baculovirus expression vectors (BEVs) by genetic modification to include a gene of interest. BEVs can replicate in lepidopteran cells and larvae, thereby efficiently transferring foreign genes into eukaryotic cells. The foreign gene is usually under transcriptional control of a viral promoter so that the gene is transcribed by the virus, but translated by the host cell biosynthetic machinery. The BEV system is one of the best tools for recombinant protein expression in a eukaryotic host and has been used for the production of many different proteins for research purposes. The BEV system also has potential industrial application for the production of proteins used in vaccines, therapeutic agents, and diagnostic reagents. Advantages of this protein production system...

Prevention and Control of Disease

Economic loss is not considerable with most of the milder forms of pig encephalomyelitis, and therefore vaccination is not considered justifiable. In addition, subclinical infections prevent the success of a slaughter policy. Both oral and parenteral vaccines have been used successfully against Teschen disease. Eradication has been achieved in one area by a combination of improved sanitary methods, slaughtering of diseased animals and ring vaccination. Virulent serotype 1 viruses have been prevented from spreading to disease-free countries by restrictions on the importation of pork products and swine. Vaccines have been prepared against SVDV, which in most countries is a notifiable disease. However, the preferred method of control is by containment and stamping out using a slaughter policy. The stability of the virus makes the eradication of the disease difficult. Following slaughter of an infected herd, premises have to be cleansed and disinfected thoroughly and possible infected...

Assessment of Disease Occurrence and Outcome

By introducing quantitative measurements of disease trends, epidemiology has come to have a major role in improving our understanding of the overall nature of disease and in alerting and directing disease control activities. Epidemiology is also effective in (1) clarifying the role of particular viruses and viral variants as the cause of disease (2) clarifying the interaction of viruses with environmental determinants of disease (3) determining factors affecting host susceptibility (4) unraveling modes of transmission and (5) field testing of vaccines and antiviral drugs.

Prevention and Control of EBV Infection

The importance of the EBV-associated malignancies in world health terms has prompted the development of a vaccine against viral infection. As the MA glycoprotein on the EBV virion is a target for neutralizing antibodies during normal infection, this molecule has been proposed as a suitable immogen for eliciting protective immunity. In the experimental cotton-top tamarin model, immunization with various preparations of MA is able to protect the animals against lymphomagenic doses of EBV. Recombinant soluble MA has now been produced and clinical trials should take place in the next few years. An important patient group to target will be those children awaiting transplantation where virus-neutralizing antibodies raised in response to MA vaccination may provide protection from the development of EBV-associated lymphomas. As the nature of primary EBV infection may make prophylactic vaccination extremely difficult, the use of therapeutic vaccines, perhaps directed to other EBV-encoded...

Revolution in Biology

Following 1953, when Thomas Watson and Francis Crick published their famous paper on the double helix structure of DNA, a series of independent discoveries were made in chemistry, biochemistry, genetics, and microbiology, which together brought about a revolution in biology and led to the first experiments in genetic engineering in 1973. Because of this revolution, scientists learned to modify living microorganisms in a permanent, predictable way. Bacteria have been made to produce medical products, such as hormones, vaccines, and blood factors, that were formerly not available or available only

Virion Structure and Properties

PV virions form a nonenveloped, icosahedral structure of 55-60 nm diameter (see Figure 4). The capsid is composed of the major capsid protein, L1, and the minor capsid protein, L2, which form 72 pentameric capsomeres with an icosahedral symmetry of T 7. The viral genome is packed in a nucleohistone complex. The L1 protein can self-assemble into virus-like particles (VLPs) VLPs present the conformational epitopes required for generating high-titer neutralizing antibodies and are the basis of very successful vaccines in humans and animals.

Genetic Variation In Echinococcus

Pathology with important implications for the design and development of vaccines, diagnostic reagents, and drugs. For example, the adult parasite of the cattle strain of E. granulosus exhibits precocious development in the definitive host with a short prepatent period of 33-35 days, nearly a week earlier than that of the common sheep strain. 6 This complicates control efforts where drug treatment of definitive hosts is utilized as a means of breaking the cycle of transmission, as it necessitates an increase in frequency of adult cestocidal treatment.

Notable Animal Papillomaviruses

Cottontail rabbit papillomavirus (CRPV) naturally infects the cutaneous epithelium of wild cottontail rabbits and is also able to infect jackrabbits and snow-shoe rabbits. In contrast, experimental infection ofdomestic rabbits results in nonproductive papillomas that support normal early viral gene expression and genome replication, but are unable to support late gene expression and virus particle production. CRPV-induced papillomas can either persist or regress, depending on host genetic factors, and persistent papillomas can progress to carcinomas in both wild and domestic rabbits. CRPV DNA can induce papillomas on scarified rabbit skin and this has allowed a genetic assessment of which viral functions are required to induce papillomas. The CRPV model has also been used for the development of preventive and therapeutic PV vaccines. neous immune-mediated regression. COPV is a good model for mucosal PV infection and has been very useful in studying the immune response and the...

Immune Response Prevention and Control

Been attenuated by passage in a clariid fish cell line is able to provide substantial protection against the lethal effect of infection by virulent CCV, particularly when the initial immunization is subsequently boosted. This virus exhibits several genomic differences from wild-type virus, most notably a substantial deletion in gene 50, which potentially encodes a secreted glycoprotein. The use of avirulent strains of virus produced by deleting specific genes may lead in the long term to an efficacious vaccine which, in being unable to revert to virulence, would also be safe. In this context, deletion of gene 5, which encodes thymidine kinase, has been shown to cause attenuation of virulence in channel catfish fingerlings. See also Antivirals Fish viruses Herpes simplex viruses (Herpesvirldae) General features, Molecular biology Latency Vaccines and immune response.

Functions of Papillomavirus Proteins

Sids in the absence of viral DNA or any other viral protein. This property has led to the production of HPV-6, HPV-11, HPV-16, and HPV-18 particles in het-erologous expression systems as prophylactic anti-HPV vaccines. The L1 protein is central to the first step of PV infections by binding to proteoglycans and integrins at the surface of epithelial target cells. The infection does not select specific target cells, and the epithelial specificity of PV infections is established by the transcriptional environment in epithelial cells.

Host Range and Viral Propagation

The most important small animals for laboratory investigations are the guinea pig and the suckling mouse. In the former, injection of virus intradermally into plantar pads results in the formation of vesicular lesions both at the site of injection and in the mouth and the remaining feet, and so resembles the lesion distribution in naturally infected susceptible species. Intraperitoneal infection of suckling mice results in rapid death and is useful for the titration of virus. The viruses can be propagated in primary cells and cell lines of bovine or porcine origin. Cells derived from the BHK-21 line are most widely used for research or vaccine production purposes. The virus can be titrated by plaque assay in cultured cell monolayers or by cytopathic endpoint dilution assay in microtitre plates.

Patents and the Rise of Biotechnology Companies

Among the new companies to take advantage of the court ruling was the Chiron corporation, which cloned the protein that formed the outer coat of the human hepatitis B virus. This protein, which could now be produced without the virus that it normally enclosed, provided the material for the development of the first human vaccine using recombinant DNA technology. The hepatitis vaccine has been available since 1987.

Frog Virus 3 iIridoviridae

Tective antigens from several poultry pathogens have been developed. For example, recombinants expressing the hemagglutinin of avian influenza and Newcastle disease virus have been shown to provide protection in vaccinated birds against the respective virulent viruses. In fact, a fowlpox virus-vectored Newcastle disease virus recombinant vaccine is commercially available but its use has been limited because of its high cost compared with that of the conventional vaccine. Thus the future of such recombinants is limited unless a polyvalent vaccine expressing antigens from several pathogens becomes available and is more cost-effective than the current vaccines.

Primary Nursing Diagnosis

Other Drug Therapy Bronchodilators, which are used for prevention and maintenance therapy, can be administered as aerosols or oral medications. Generally, inhaled anticholinergic agents are the first-line therapy for emphysema, with the addition of beta-adrenergic agonists added in a stepwise fashion. Antibiotics are ordered if a secondary infection develops. As a preventive measure, influenza and pneumonia vaccines are administered.

EncephalitisDRG cew 020

Encephalitis has two forms primary and postinfectious (or parainfectious). The primary form of the disease occurs when a virus invades and replicates within the brain. Postinfectious encephalitis describes brain inflammation that develops in combination with other viral illnesses or following the administration of vaccines such as measles, mumps, and rubella. In that case, encephalitis occurs because of a hypersensitivity reaction that leads to demyelination of nerves.

The Growth of Specialization

Previously, most publications put so little emphasis on science that they did not need a specialized reporter. More and more, though, news organizations regard scientific results as necessary information, part of the everyday reporting of news. After all, science and technology have radically altered the way we live. For example, consider the development of antibiotics and vaccines, nuclear weapons, computer technologies, lasers, and fiber optics. Advances in science and technology will undoubtedly continue to occur in ways that we can not fully predict. The Human Genome Project, with all its promise and ethical unknowns, illustrates this perfectly.

Uses of Genetic Engineering of Animal Viruses

Practical applications of genetic engineering of viruses include the development of nucleic acid probes for diagnosis and novel methods for the production of vaccines, such as the use of vaccinia virus as a vector. Combined with the availability of simple and fast methods of sequencing nucleic acids, genetic engineering has also led to studies of animal virus genomes that could not be contemplated before it became possible to produce large quantities of selected fragments of viral nucleic acid by the use of the polymerase chain reaction. Among the achievements so far are

Prevention and Control of Infection

Inactivated cell-culture derived and rodent brain-derived vaccines for HFRS have been developed, tested, and are licensed for use in Asia. Preliminary information suggests that these vaccines are well-tolerated and that they can elicit antibody responses detectable by ELISA. Some of the vaccines also elicit neutralizing antibody responses in humans. Controlled efficacy studies have not been reported. A recombinant vaccinia virus vaccine for HFRS was developed in the US and tested in phase I and phase II clinical trials. The vaccine elicited neutralizing antibodies in the majority of vaccinia-naive individuals but not in vaccinia preimmunes. Other genetically engineered vaccines are under development but have not yet been tested in humans.

Basic and Applied Research

In addition to carrying out basic research, molecular biologists may also work in applied research. Using recombinant DNA technology, for example, molecular biologists have created economical vaccines against deadly diseases. The molecular biologist often works at the frontier or cutting edge of a discipline. The rewards of such work include the thrill of intellectual discovery and the opportunity to conduct independent research. Also, the efforts of molecular biologists can bring great benefits to society.

Epidemiology and Control

To reduce disease prevalence, vaccination with live-attenuated or inactivated vaccines has also been used. However, vaccination does not result in sterile immunity, and vaccinated animals may still be infected with and carry the virus, and these carriers are no longer identifiable by serological analysis. This problem has been solved by the advent of the so-called 'marker' vaccines. This novel concept provided a breakthrough in animal disease control, and serves as a blueprint for control of other infectious diseases. It was based on the finding that several immunogenic envelope glycoproteins of PrV, such as gC, gE, and gG (see above), are not required for productive replication and can be deleted from the viral genome without abolishing virus replication. These gene-deleted strains can be produced easily in conven tional cell systems and can be administered as inactivated or modified-live vaccines. In fact, gene-deleted PrV strains were the first genetically engineered live-virus...

PrV as a Tool in Neurobiology

Like other alphaherpesviruses, PrV exhibits a distinct neurotropism, invading the CNS via peripheral nerves. While wild-type strains of PrV may spread within the CNS both laterally and transsynaptically, attenuated PrV mutants have been identified which, under appropriate assay conditions, travel more or less exclusively along nerves and are transported transsynaptically. This property has prompted increasing use of PrV as a transneuronal tracer to label neuronal connections in experimental animal models, and has been useful in elucidating detailed neuroanatomical networks in mice and rats. The virus used most frequently in these studies is the Bartha strain of PrV, a modified-live vaccine strain which had been attenuated by the Hungarian veterinarian Adorjan Bartha by multiple passages in embryonated chicken eggs and chicken embryo fibroblasts. Molecular biological analyses demonstrated that this strain carries several lesions compared to wild-type PrV it lacks the gE, gI, and US9...

Future Trends in Research on HSV

HSV possesses a number of features that will make it a continuing research model in the future. Among the most obvious are the following. (1) The neurotropism of the virus, along with the relative convenience of generating recombinants containing foreign genes expressed either under homologous or heterologous promoters, recommends HSV as a vector for introducing specific genes into neural tissue. This facility is increased by the fact that the viral genome can enter and be maintained in neural tissue in the complete absence of lytic phase viral gene expression. (2) The fact that HSV's replication is restricted in terminally differentiated neurons suggests its potential as a therapeutic agent against neural tumors, provided appropriate mutants can be constructed. (3) The benign nature of normal infection with HSV also suggests its potential use as a vaccine vector by incorporation of specific antigens into the viral

Properties of the Viral Proteins

The nonstructural Npro is a protease with autopro-teolytic activity it has no counterpart in flaviviruses. The nucleocapsid protein (C) precedes the three envelope glycoproteins. The Erns protein (formerly called gp42) forms a disulfide-linked homodimer. The mechanisms by which it is associated with the virion is unknown it is also secreted from infected cells. A remarkable feature of Erns is its RNase activity, which is unique among viruses. The function of this enzymatic activity is as yet unclear. The Erns protein exhibits a strong immunosuppressive effect in vitro, and elimination of the RNase activity results in a cytopathogenic virus (HCV is normally noncyto-pathogenic). The El protein (gp31) is, as a disulfide-linked E1-E2 heterodimer, present in the viral envelope, and the E2 (gp53) as a disulfide-linked homodimer and as a heterodimer with El. The E2 protein is composed of at least four antigenic domains, three of which give rise to neutralizing antibodies. The E2 protein...

Pathogenicity and Virulence

Although there is a continuous spectrum of virulence of HCV strains, one can distinguish strains of high, intermediate and low virulence, whereas the HCV vaccines are avirulent. It is not known which viral genes are involved in the expression of virulence. The severity and outcome of infection is the result of the composite interaction of viral virulence and host factors, such as breed, age, nutritional condition and immune competence. An association may exist between virulence and antigenicity strains that are antigenically more related to BVDV seem to be less virulent. Low-virulent strains may grow optimally at 33-34 C, whereas virulent strains do so at about 39-40 C. The growth of virus in porcine alveolar macrophage cultures has been used as a marker for virulence. Virulent virus may grow to higher titers in vivo and in vitro than low-virulent strains. Whereas virulent virus thoroughly infects epithelial cells, reticular cells and macrophages in the tonsil, growth of virus of...

Cysteine Proteases As Targets For Disease Intervention

EhCPs forms a particularly good target for disease prevention and intervention for a number of reasons. Firstly, they are essential for the parasite life cycle in terms of encystation, excystation and nutrient acquisition, so any disruption in the CPs involved in these processes would affect parasite viability. Furthermore, CPs are one of the key virulence factors involved in intestinal colonization and invasion, disruption ofhost tissue and modulation of cell-mediated immune responses,53,121 so prevention of these would have a significant impact on disease pathogenesis. Finally, EhCPs are easily inhibited by chemical means, or silenced with the use of antisense RNA and the presence of conserved sites provides potential targets for vaccine development. A number ofnatural and synthetic inhibitors against EhCPs have been identified a summary of which can be found in reference 7. Thus E. histolytica CPs provide attractive targets for novel chemotherapeutic intervention122 and CP...

HIV Cellmediated Immunity

Infection with HIV poses a particular problem for immunity for two reasons. The first is that the viral coat glycoproteins vary greatly, which limits the effectiveness of vaccines depending on the presence of pre-existing neutralizing antibody. The second is that the cell surface receptor for HIV is the CD4 molecule expressed on the helper T cell and, in humans, on some macrophages. Chemokine receptors have recently been identified as coreceptors for HIV infection. The development of the acquired immune deficiency syndrome (AIDS) is associated with the progressive, inexorable loss of the CD4+T cells. At least part of this may reflect elimination of the infected CD4+T cells by the virus-specific CD8+T cells, which remain fully functional CTL effectors during the course of this persistent infection. Also, stimulation of the CD4+T cells activates the virus growth cycle and thereby increases viral load. A further complicating factor is that virus reservoirs persist in association with...

History or How We Got to Where We

The first vaccine, introduced for smallpox by Jenner (1798), depends on CMI effector mechanisms. Systematic analysis of the ectomelia (mousepox) model by Fenner (1947) set the stage for modern studies of CMI, with Blanden showing some years later (1970) that primed Thy-1+ cells promote virus clearance. Recombinant poxvirus (vaccinia) tech nology has also been used very effectively for the identification of the antigenic proteins peptides involved in virus-specific T cell recognition. This approach (pioneered by Paoletti and Moss) has led to practical consequences, for example the recombinant rabies vaccine developed by Koprowski and his colleagues for use with feral populations. See also Autoimmunity Cytomegaloviruses (Herpesviridae) Animal cytomegaloviruses, General features (human), Molecular biology (human), Murine cytomegaloviruses Epstein-Barr virus (Herpesviridae) General features, Molecular biology Human immunodeficiency viruses (Retro-viridae) Molecular biology,...

Diagnosis Prevention and Control

Using a 2 bleach solution to interrupt animal-to-animal spread, and insect control measures can be introduced. Vaccines against VSIV and VSNJV have been used to control outbreaks in Central and South America. Although vaccination is not routinely practiced throughout the Americas, experiments demonstrate a substantive decrease in clinical infections in vaccinated animals.

Clinical Features of Infection

In humans, influenza is characterized by the sudden onset of an acute respiratory illness with headaches, chills and nonproductive cough, followed by high fever, muscle aches, generalized weakness and loss of appetite. The fever declines by the third day and is usually gone by the sixth day, but cough and weakness can persist for an additional 2 weeks. More severe illness can develop if primary influenza pneumonia or secondary bacterial pneumonia occurs. People over 65 years of age and those with health problems, such as heart conditions, emphysema, asthma or acquired immune deficiency syndrome (AIDS), and children and adults receiving cancer chemotherapy are at increased risk for complications from influenza and should receive yearly vaccination. At least 10000 excess deaths (over expected) have been documented in each of 19 different US epidemics in the period 1957-1986 in three epidemics there were > 40 000 excess deaths. Approximately 80-90 of the excess deaths attributed to...

Prevention and Control of Influenza

Two options are available for the control of influenza A virus vaccination or therapy with influenza specific antiviral agents. With increased global surveillance by the World Health Organization, vaccines and epidemic strains are usually well matched and effective at providing protection against influenza A and B. The available vaccines include purified inactivated egg-grown whole virus or purified surface antigens. Only surface antigens (subvirion vaccines) are recommended for children under 12 years, because the whole-virus vaccine causes febrile responses in children. Persons with known allergies to eggs should not be given egg-grown vaccine. Cold-adapted attenuated live influenza vaccines have been shown to be safe and effective in experimental trials and are currently under review for licensing for general use.

Structure of the Hemagglutinin HA

In type A influenza virus, the HA accounts for about 25 of the viral protein. It is responsible for the attachment of virus to cells and for the penetration of the virus into the cell during the initial stages of infection. Antibodies to the HA neutralize the infectivity of the virus. Variation in the HA glycoprotein is mainly responsible for the continually occurring outbreaks of influenza and for our inability to control these by vaccination.

Detailed Consideration of Dominantnegative Mutants

Live virus vaccines should contain dominant negative mutations In this connection it should be noted that the ability to interfere with the growth of wild-type virus would be a particularly desirable trait in the case of live virus vaccines. The use of vaccine viruses with attenuating mutations that also confer a dominant-negative phenotype would add a significant degree of protection against virulent revertants that may arise during the immunizing infection or against epidemic viruses that may be circulating concurrently in the population. In addition to their immunizing potential, dominant-negative vaccine viruses could offer short-term antiviral protection until the immune response to the virus is firmly established. Whitaker-Dowling P, Maassab HF and Youngner JS (1991) Dominant-negative mutants as antiviral agents simultaneous infection with the cold-adapted live-virus vaccine for influenza A protects ferrets from disease produced by wild-type influenza A. J. Infect. Dis. 164 1200.

Evolution and Genetics

Serological investigations have demonstrated that sera collected from individuals prior to the use of SV40-contaminated polio and adenovirus vaccines contained antibodies to JCV and BKV. This finding eliminated any suspicion that the high prevalence of anti-JCV and anti-BKV antibodies in today's population is due to exposure to SV40 in vaccines. Based on the extent to which the human and monkey viruses have diverged, it is evident that the viruses have not recently evolved from one another.

Avian Influenza in Thailand

Thailand first recognized the massive die-offs of poultry by late 2003, and the government officially reported the outbreak of H5N1 pathogenic influenza virus on January 23, 2004. At present, the country had already passed three waves of the epidemics. Outbreaks mostly occurred in the central and eastern parts of the country where water reservoirs and wetlands are abundant and poultry population is dense. The outbreaks also happened when the weather was wet and cool. Poultry vaccination is prohibited in Thailand. Pre-emptive depopulation and several means of biosecurity measures have been applied to control the outbreaks. Free-grazing ducks, fighting cocks and backyard chickens remain to be the major problems of the country. Of all three outbreaks, there were 22 human cases with 14 deaths which made the fatality rate 63.6 . The disease was more fatal in children than adults. The infection also spread to other mammalian species tigers, leopards and cats. Phylogenetic analysis revealed...

Taxonomy and Classification

Species is subdivided into four subtypes Zaire, Sudan, Cote d'lvoire and Reston. In terms of biohazard classification, filoviruses are classified as Biosafety Level 4 (BSL4) agents based on their high mortality rate, person-to-person transmission, potential aerosol infectivity, and absence of vaccines and chemotherapy. Maximum containment is required for all laboratory work with infectious material.

Distribution and Epizootiology

A number of stresses, including handling, change of housing, vaccination and debeaking, have been anecdotally associated with exacerbation of clinical MD in infected flocks, and experimental studies have shown that the stress induced by changes in social hierarchies of birds ('pecking orders') and genetically controlled responses to stress, as measured by corticosterone levels, can influence the incidence of disease.

Measles Virus iParamyxoviridae

Development of recombinant vaccines needed to improve protection against disease. Interest is also focused on understanding the complex pathogenesis of MD, particularly the role of T cell subsets, and other cells, involved in transformation and immunity. Lastly, work on genetic resistance to MD continues, for the light it throws on the disease process, for understanding interactions between host genotype and vaccination, and because the availability of transgenic techniques in chickens means that development of genetically resistant chickens by this method offers an alternative to vaccination in disease control. viruses (Herpesviridae) General features, Molecular biology Immune response Cell mediated immune response, General features Vaccines and immune response. immunity, even in the absence of re-exposure to the virus. Consequently, to remain endemic in a given community the virus has to infect the young who are still susceptible. This process is so efficient that the first known...

Geographic and Seasonal Distribution

Measles occur worldwide and are endemic in regions with inadequate vaccine coverage. The efficiency of transmission is high and outbreaks have been reported in populations where as few as 3 7 of individuals are susceptible. There is generally no seasonal distribution of measles epidemics. The disease incidence in the northern hemisphere tends to rise in winter and spring when lowered relative humidity would favor respiratory transmission. In equatorial regions epidemics of measles can occur in the hot dry seasons. In large unimmunized populations, measles epidemics occur at regular intervals, and the number of susceptible individuals or the frequency of contact between infectious and susceptible individuals will lead to an increase in measles cases.

Genetics and Evolution

The monotypic nature of MV in serological terms has masked the existence of a set of genotypes which accumulate mutations continuously. During the recent past, the molecular epidemiology of MV has been intensely studied to reveal whether MV strains differ in pathogenicity or to monitor the antigenic drift in wild-type MV strains. Sequence analyses on vaccine and wild-type MV strains as well as isolates from persistent MV central nervous system (CNS) infections (SSPE) have enabled the construction of evolutionary trees that clearly indicate their relationship. The sequence of the COOH-terminal 151 amino acids of the N protein of 46 strains of MV revealed an up to 7.2 divergence in the coding sequence and 10.6 divergence in the amino acid sequence between the most unrelated strains. MV strains group into several different genotypes some of which are extinct (i.e. have not been isolated recently) or are still cocirculat-ing in the human population. The vaccine strains differ markedly...

Clinical Features and Infection

About 10 days after exposure the patient enters the prodromal phase which lasts from 2 to 4 days. The initial symptoms consist of fever, malaise, sneezing, rhinitis, congestion, conjunctivitis and cough. At the beginning of the prodromal stage, a transitory rash can sometimes develop which has an urticarial or macular appearance, but disappears prior to the onset of the typical exanthem. Once the exanthem has reached its height, the fever usually falls and the conjunctivitis as well as the respiratory symptomatology begin to subside. Antibody titers rise, virus shedding then decreases and the patient rapidly improves. Continuation of clinical symptoms of the respiratory tract or fever suggests complications (Table 2). Modified measles occur in partially immunized hosts such as infants with residual maternal antibodies or in the course of live vaccine failure. The illness is mild and follows the regular sequence of events seen in acute measles but is less symptomatic. Atypical measles...

Mink Enteritis Virus see Parvoviruses

Progress made in the molecular biology of MV could lead to the development of genetically engineered measles vaccines which should be free of side effects and possibly suitable for the immunization of individuals currently at greatest risk, such as young infants or those suffering from chronic debilitating diseases.

Virulence Factors And Immunomodulators

L. mexicana mutants lacking both CATL-A and CATL-B genes did not induce lesion growth in BALB c mice, indicating that a combination of enzymes with CATL-like activities was required for establishment of infection.118 Also, in mice infected with such mutants there was a shift from a Th2-type to a Th1-type immune response. When these CATL-deficient parasites were tested as vaccines in different strains of mice they induced various degrees of protection from challenges with wild type L. mexicana.118 In hamsters the CATL-deficient mutants delayed onset of disease as recorded by smaller lesions and lower parasite burden.125 Finally, for LmeCATB mutants, infectivity to macrophages was decreased in vitro and in vivo and the resulting lesions were smaller.126

Lamivudineassociated Mutations In The Hbv S Gene

Four open reading frames, the S, C, X, and P genes, have been identified within the HBV genome. Because of the overlap of the P and S genes, lamivudine-associated mutations produce changes in the S gene, too. Consequently, lamivudine-resistant HBV isolates show alterations in the ''a'' determinant of the HBsAg protein. 16 Lamivudine-selected HBsAg protein changes may have important virological and clinical implications They may escape neutralization by vaccine-induced anti-HBs antibodies and thus may have the potential to become vaccine escape mutants. Widespread use of lamivudine may lead to infection of vaccinated individuals and potentially reduce the efficacy of current HBV vaccines.

The Importance of SNPs

Mutation suggests a nucleotide change that prevents a protein from performing its normal function. These mutation-caused changes are rare, occurring in less than 1 percent of the population. This type of genetic mutation is almost always severe enough that its presence alone is enough to cause the disease. In contrast, SNPs are much more common, certainly occurring in more than 1 percent of the population. Their presence may make it easier for a person to get a specific disease, but they do not cause the disease by themselves. Instead, disease can occur only in the presence of the correct environment, other gene combinations, drugs, and other such factors. This is very important, for it suggests that by knowing that an individual is at risk for a disease, a doctor can take actions to prevent it. These actions may be as simple as a dietary or lifestyle change, or taking a medicine or vaccine.

Description Medical Coagulation Disorders

Acute ITP is thought to be a response to a viral infection. Generally, a viral infection, such as rubella or chickenpox, occurs 2 to 21 days before the onset of the disease. Acute ITP may occur after live vaccine immunizations and is most prevalent during the winter and spring months when the incidence of infection is high. It is also associated with human immunodeficiency virus (HIV). Chronic ITP generally has no underlying viral association and is often linked to immuno-logic disorders, such as lupus erythematosus, or to drug reactions. HISTORY. Ask if the patient has recently had rubella or chickenpox or a viral infection with symptoms such as upper respiratory or gastrointestinal (GI) symptoms. Ask if the patient was recently immunized with a live vaccine. Check for a history of systemic lupus erythematosus easy bruising or bleeding from the nose, gums, or GI or urinary tract. Because the symptoms of chronic ITP are usually insidious, patients may not have noticed an increase in...

Generation of Blood Derived Human Dendritic Cells for Antitumor Immunotherapy

Samples of blood, where the frequency of CD34+ cells is very low (0.1 ). A major breakthrough came with the description of a simple method to generate large numbers of blood-derived DC from monocytes by culture with granulo-cyte-macrophage colony stimulating factor (GM-CSF) and IL-4 (3,4). This allowed the design of immunotherapeutic strategies using ex vivo-generated DC as adjuvants (5,6). Although reaching a good level of maturation at d 7, these culture conditions involved xenologous sera such as fetal calf serum (FCS), which may be suboptimal in clinical applications. FCS-free autologous conditions necessitate an additional maturation step for the generation of mature DC. In this two-step culture system peripheral blood mononuclear cells (PBMC) are first differentiated in autologous-plasma-supplemented medium with addition of GM-CSF and IL-4 for 7 d and then stimulated for three additional days with monocyte-conditioned medium (MCM) (7,8). This completely autologous culture system...

Newcastle Disease Virus Paramyxoviridae

This disease, with a mortality usually less than 15 , was first called pneumoencephalitis but was later shown to be caused by a virus which was indistinguishable immunologically from Newcastle disease virus (NDV). The observation that NDV was not always highly pathological was important and was followed by numerous reports of other strains with low virulence. Such isolates were used later as live vaccines.

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