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One of the difficulties in controlling foot and mouth disease by vaccination is the occurrence of the virus as seven distinct serotypes because immunity conferred by vaccination against one serotype leaves the animals susceptible to infection by the other six. Moreover, the antigenic variation, even within a serotype, can be so great that immunity against the homologous strain of virus need not necessarily ensure protection against infection by other viruses within that serotype. Here we report the separation of three natural antigenic variants, distinguishable in cross-neutralization tests from an isolate of foot-and-mouth disease virus (FMDV). The serological differences could also be demonstrated by antisera elicited by synthetic peptides corresponding to residues 141-160 of the capsid polypeptide VP1, showing that this region contains a major immunogenic site of the virus. The results have practical implications for the choice of viruses for vaccine production.

Peptides from different regions of the poliovirus type 1 capsid protein VP1 were synthesized. Antibodies raised against these peptides in rabbits and rats recognized the cognate peptides and denatured VP1. Peptides from four regions of VP1 generated antisera with neutralizing titers specifically against poliovirus type 1. Antisera against all other regions of VP1 failed to neutralize virus infectivity, although some of the antisera clearly bound to native virions. Thus, the neutralizing determinants on VP1 reside in specific noncontiguous regions of the protein and can be defined by specific peptides from these regions. An animal's immunologic response against a viral antigen is a composite of many antibodies, of which those that neutralize infectivity comprise a specific subset. Because the neutralizing response plays a major protective role, the characterization of the antibodies, their specificities, and their functional role in the neutralization process is crucial to an understanding of the pathobiology of a virus. In addition, the definition of neutralizing epitopes should help in the understanding of initial virus-cell interactions.It previously has been shown that major neutralizing determinants are found on the poliovirus type 1 capsid protein designated VP1. The isolated, denatured VP1 is capable of inducing virion-neutralizing antibodies in rats (1) and rabbits (2). VP1 is immunoprecipitated by a neutralizing anti-virion monoclonal antibody, C-3 (3). In addition, using this monoclonal antibody, Wychowski et al. (4) have shown that a neutralization epitope was located within the region of amino acid residues 90-104 of VP1. Analysis of virion mutants that are resistant to neutralizing anti-virion monoclonal antibodies showed that a major neutralizing determinant for poliovirus type 3 was localized within VP1 in the region of amino acid residues 96-106 (5, 6). Characterization of a large set of neutralizing anti-virion monoclonal antibodies against poliovirus type 1 also indicated that the amino acid region 94-104 of VP1 contained a neutralizing determinant (7). In addition, an additional amino acid region (residues 70-80) was recognized by some monoclonal antibodies (7). Thus, it appears that VP1 potentially possesses several neutralizing determinants.To further characterize the neutralization response against VP1 and to structurally characterize the neutralization epitopes, we derived a partial antigenic map of VP1, using antisera made against synthetic peptides from different regions throughout the VP1 protein. We report here that synthetic peptides spanning four separate regions of the VP1 sequence will induce neutralizing antibodies. These serotype-specific antibodies recognize VP1 and the intact mature poliovirus virion. The ability of these four regions to generate neutralizing antibodies is independent of the choice of immunizing host. METHODSSynthesis and Coupling of Peptides. The peptides were synthesized by R. Houghten, with solid-phase methods using a Beckman model 990B peptide synthe...

Six specific-pathogen-free cats were exposed by aerosol to a feline calicivirus of low virulence (F-9 virus). Homotypic (anti-F-9) seroconversion occurred in all cats by postexposure day 14. The serum of one cat on postexposure day 14 and four of six cats on postexposure day 35 neutralized feline picornavirus isolate no. 255 (FPV-255), a virulent feline calicivirus. Homologous antiviral activity was detected before the appearance of heterologous (anti-FPV-255) activity and always was present in higher titer. Protective immunity was evaluated on postexposure day 35 by aerosol challenge with FPV-255. The pyrexia, depression, dyspnea, oral ulcers, and severe pneumonia produced in two susceptible specific-pathogen-free cats by exposure to FPV-255 did not occur in the cats that had been infected previously with F-9 virus. The study demonstrates that heterotypic protective immunity to feline calicivirus disease can be induced by prior infection with feline calicivirus of low virulence.