Cattle

Natural immunity of cattle following recovery from FMD infection is sometimes used as the benchmark by those workers who seek to improve on conventional inactivated whole virus vaccines. According to the popular definition of the serotypes of FMD, cattle which have recovered from infection with one of the seven serotypes are not immune to the other six. However, it is not commonly known that further rounds of infection with other serotypes may result in less severe clinical responses or even...

Subject Index

Acid treatment 81 adenovirus 144 Aepyceros melampus 12 aerosol 17, 18, 20 - virus 137 AIDS 150, 153, 163 airborne transmission 17, 19 aluminium hydroxide 122 amino acid sequence 151 antigen 122 - structure 111 aphthovirus 3, 9, 46, 58, 90 arteriodactyla 10 - translation initiation codon 157 bacteria-proof filter candle 2 B-helper cell epitope 145 binary ethylene imine (BEI) 7 blood lymphocyte 124 bovine - immune system 109 Bubalus bubalis 12 bus 48 C Oberbayern virus 121 calicivirus 6 -...

Preface

Foot-and-mouth disease (FMD) has been recognized in printed records dating from the sixteenth century, and since the eradication of rinderpest (cattle plague) in the early part of the twentieth century it has been recognized as the most important and feared disease of cattle and other domestic livestock. The beginning of the twenty-first century brought the worst outbreak of FMD ever experienced in England, which had been completely free of the disease for 33 years. This tragic epidemic, which...

Mucosal Antibody Response and the Carrier State

Mucosal immune responses of cattle due to parenteral vaccination are very different to those seen with infection. After oil emulsion vaccine, ELISA of pharyngeal fluid showed a rapid development of IgG but more delayed IgM response (Francis et al. 1983). Vaccinations at approximately 60-day intervals produced a series of IgM and IgG peaks, but at no time was IgA apparent, in contrast to parallel experiments with infected animals. Neutralising activity in the pharyngeal fluid did not appear to...

Accumulation of Deleterious Mutations Rate Mode Mechanisms

Several concepts of population genetics have been very useful for the understanding of quasispecies dynamics. One of these is the accumulation of deleterious mutations in asexual populations of organisms when no compensatory mechanisms such as recombination intervene, a process termed Muller's ratchet (Muller 1964 Maynard-Smith 1976). The operation of Muller's ratchet was first documented with an RNA virus by Lin Chao (Chao 1990) working with phage f6. These results were then extended to VSV...

Viral Antigens and Epitopes

Our knowledge of viral antigens and antigenic structures which are recognised by the immune system owes much to in vitro studies with sera from infected, but particularly, vaccinated animals and will be reviewed also within the vaccination section of this paper. However, there is no evidence to suggest that the immune response to infection is fundamentally different to that to vaccination in terms of the antigens which are recognised. It is clear that the host immune system recognises a number...

Routes of Infection

Most of our understanding of the routes of infection derives from experimental studies in animals infected with FMDV by simulated natural methods (by direct or indirect contact with infected animals, contaminated products or fomites or by exposure to virus aerosols from infected animals) or in animals infected by artificial methods, including direct injection of virus. From these studies the minimum infective doses for the main livestock species infected by different routes can be estimated....

Genotypes

With the development of techniques for nucleotide sequence analysis, comparison of the nucleotide sequences of the capsid protein genes from many FMD viruses from different geographical sites of isolation showed that there was good correspondence with serotype differences, the sequences clustering into serotype-specific lineages upon phyloge-netic analysis. The seven serotypes of FMDV cluster into distinct genetic lineages with approximately 30 -50 differences in the VP1 gene (Knowles and...

Introduction

Despite the dramatic advances in our understanding of viral pathogenesis and the development of vaccine technology brought about by the enlightenment of the most intimate secrets of how viruses interact with their host cells, foot-and-mouth disease (FMD) virus remains a major threat to the most sophisticated economies of the world. The combined threats of free trade and bio-terrorism have shown how vulnerable the agricultural industries of North America and Europe are to attack by one of the...

Pathology

Very early lesions are only detectable by microscopical examination (Gailiunas 1968 Yilma 1980), and it is characteristic that even apparently normal skin with no macroscopical or histopathological changes may contain significant amounts of virus (Alexandersen et al. 2001). The first histopathological changes can be observed in the cornified, stratified squamous epithelium and are characterised by ballooning degeneration and increased cytoplasmic, eosinophilic staining of the cells in the...

Primary and Secondary Sites of Infection

As mentioned above, the pharyngeal area is the usual primary site of infection except when the virus directly enters into the cornified epithelia or the circulation by damage to the intact integument (Garland 1974 McVicar and Sutmoller 1976 Burrows et al. 1981). In contact- or aerosol-exposed animals, virus may be demonstrated in the pharynx for 1 to 3 days before a viraemia or clinical disease can be detected (Burrows 1968a McVicar and Sutmoller 1976 Burrows et al. 1981 Alexandersen et al....

Serotype O

FMD caused by serotype O has always been the most dominant and most widely distributed. It has the reputation of being the most aggressive serotype and the most difficult to control by vaccination, although so far there is no genetic explanation as to why this serotype is so invasive. Some of the strains are clearly catholic in their host range, appearing equally virulent and transmissible in sheep, goats, pigs and cattle, whereas others, like those of the Cathay topotype, will only cause...

The 3C Protease

The FMDV 3C protease is responsible for most of the proteolytic processing of the viral polyprotein. It functions alone and, in contrast to the PV 3C protease (see Ypma-Wong et al. 1988), does not require 3D sequences for any of its processing activities. The key catalytic residues of the FMDV 3C have been identified (Grubman et al. 1995), and the protease is a member of the trypsin-like family of serine proteases (except that the active serine is replaced by a cysteine). In addition to...

The SFragment

The 5'-UTR of FMDV RNA contains several discrete regions (Fig. 2). The first portion (ca. 350 nt) is called the S-fragment and is predicted to fold into a large hairpin structure (Clarke et al. 1987 Escarmis et al. 1992), but its function is unknown. It is assumed to be required for RNA replication, but it has been little studied. In contrast, at the 5'-end of the PV RNA is a much better-characterised 'cloverleaf structure. This structure is only about 80 nt long and has been shown to interact...

Natural and Vaccine Induced Immunity to FMD

Merial Animal Health Ltd., Ash Road, Pirbright, Woking, Surrey, GU24 0NQ, UK tim.doel merial.com 1 Natural Immunity 104 104 1.2 Sheep and Goats 105 106 1.4 Serum Antibody Response 106 1.5 Mucosal Antibody Response and the'Carrier State' 108 1.7 Viral Antigens and Epitopes 111 2 Vaccine-Induced Immunity 112 2.1 FMD Vaccines and Vaccination 113 2.2 Serum Antibody Response 114 2.3 Maternally Derived Immunity 116 2.5 Mucosal Antibody Response and the'Carrier State' 119 2.6 The Secondary Immune...

FMD Vaccines and Vaccination

With modern FMD vaccines made under European standards of Good Manufacturing Practice (GMP), the virus is produced in large-scale suspension cultures of baby hamster kidney cells (BHK-21) and the clarified product is inactivated with an aziridine, binary ethyleneimine, with a double-dose, two-tank process (Bahnemann 1990). In the author's company, the inactivated antigen is concentrated by ultrafiltration and then purified2 by industrial scale chromatography to remove extraneous proteins...

Sheep and Goats

Despite the recognised importance of sheep and, almost certainly, goats in the epidemiology of FMD, relatively little is known of their immune response to infection. Virus-neutralising antibodies appear 60 h after inoculation of sheep reaching a maximum titre around 10 dpi. Titres decrease slightly after day 10 but generally remain at a plateau for at least 147 days (Dellers and Hyde 1964). The carrier state may develop in sheep and goats, and virus has been recovered in oesopharyngeal...

Resistance to Extinction Despite Accumulation of Mutations Observations and Modeling

Despite a nearly linear accumulation of mutations in FMDV clones subjected to plaque-to-plaque transfers, the virus showed a remarkable resistance to extinction. An FMDV population (obtained either from a plaque or from an infection in liquid culture medium) is considered extinct when, upon at least three blind passages in cell culture under optimal infection conditions, no infectivity and no FMDV-specific RT-PCR-ampli-fiable material can be recovered. The amount of infectious virus found in...

Investigations of Possible Vectors of the Disease

After the major epizootic of FMD in the UK in 1967-68 many investigations were made into the susceptibility of small British mammals to infection with the virus. This work had two main purposes, i.e. the identification of possible vectors of the virus resulting in a mechanism for the transmission of infection to farm livestock and also the possibility of identifying additional species useful in laboratory investigations. Investigations were undertaken at the Animal Virus Research Institute,...

The Secondary Immune Response and Duration of Immunity

One of the more striking variations in the immune response to FMD vaccines is the extent to which it is boosted by subsequent vaccinations. The increase in neutralising antibody titre may often exceed 1.5 log10 (Pay 1984) whereas little or no boosting of the immune response is apparent in the data from some other reports (Francis et al. 1983 Rocha et al. 1983), suggesting that the initial and subsequent vaccinations did not stimulate the development of immunological memory. This prompts the...

References

Abu Elzein EME, Crowther JR (1981) Detection and quantification of IgM, IgA, IgG1 and IgG2 antibodies against foot-and-mouth disease virus from bovine sera using an enzyme-linked immunosorbent assay. J. Hyg. Camb 86 79-85 Ahl R, Haas B, Lorenz RJ, Wittmann G (1990) Alternative potency test of FMD vaccines and results of comparative antibody assays in different cell systems and ELISA. In Report of the Session of the Research Group of the Standing Technical Committee of the European Commission...