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Title: A SYNTHETIC PEPTIDE CONTAINING THE CONSENSUS SEQUENCE OF THE G-H LOOP REGION OF FMDV TYPE O VP1 COMBINED WITH A PROMISCUOUS T-HELPER EPITOPE INDUCES PEPTIDE-SPECIFIC AB BUT FAILS TO PROTECT CATTLE AGAINST VIRAL CHALLENGE

Author
item Rodriguez, Luis
item Barrera, Jose
item Kramer, Edward
item LUBROTH, JUAN - USDA, APHIS, PIADC
item BROWN, FRED - FORMER ARS EMPLOYEE
item Golde, William

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/23/2003
Publication Date: 9/1/2003
Citation: RODRIGUEZ, L.L., BARRERA, J.D., KRAMER, E., LUBROTH, J., BROWN, F., GOLDE, W.T. A SYNTHETIC PEPTIDE CONTAINING THE CONSENSUS SEQUENCE OF THE G-H LOOP REGION OF FMDV TYPE O VP1 COMBINED WITH A PROMISCUOUS T-HELPER EPITOPE INDUCES PEPTIDE-SPECIFIC AB BUT FAILS TO PROTECT CATTLE AGAINST VIRAL CHALLENGE. VACCINE, VOLUME 21: 3751-3756, 2003.

Interpretive Summary: The USDA needs to respond promptly to relevant requests for testing novel vaccines with potential for use in facing FMD outbreaks in the United States. This manuscript describes the results of a pilot study in cattle of a vaccine candidate containing a synthetic peptide comprising the major immunogenic sites of the foot-and-mouth disease virus. Two groups of cattle were inoculated intramuscularly either once or twice with 50ug of the peptide preparation at a 21-day interval. A third group of cattle served as non-inoculated control. The animals were challenged 21 days after the last inoculation with FMDV type O-Manisa. None of the inoculated animals was protected upon challenge and presented with full-blown FMD as did non-inoculated control animals. In contrast, 4 of the 5 animals inoculated with a traditional inactivated FMD type O commercially prepared vaccine were fully protected against challenge. We conclude that although the synthetic peptide induced an antibody response in cattle, it failed to confer protection against FMDV challenge.

Technical Abstract: A pilot study was carried out in cattle to determine the immunogenicity of a synthetic consensus peptide comprising the G-H loop region of Foot-and-Mouth Disease Virus (FMDV) type O VP1 and a non-VP1 T-helper epitope. Cattle were vaccinated intramuscularly either once (n=5) or twice (n=4) with 50ug of the peptide preparation at a 21-day interval and compared with non-inoculated control animals (n=3). The animals, housed in the same room in direct contact throughout the study, were challenged 21 days after the last inoculation with 104 bovine-infectious units of FMDV type O-Manisa. All vaccinated animals developed antibodies to the peptide as determined by ELISA with the exception of one steer that received a single dose vaccination. Neutralizing antibody titers against FMDV type-O were minimal but detectable in most peptide vaccinated animals. All animals vaccinated with the peptide formulation, as well as naïve animals, presented with clinical signs of FMD upon challenge. In contrast, 4 of the 5 animals inoculated with an inactivated FMD type O commercially prepared vaccine developed neutralizing antibodies and were fully protected against clinical disease following virus challenge. Interestingly, despite having neutralizing activity, pre-challenge sera from these vaccinated cattle failed to recognize the VP1 synthetic peptide by ELISA. Nucleotide sequencing of the VP1 region of the challenge virus and a virus recovered 5 days post challenge from nasal swabs of a peptide-vaccinated animal with detectable neutralizing antibodies showed no evidence for selection of neutralization-resistant mutants. We conclude that although the synthetic peptide induced an antibody response in cattle, it failed to confer protection against FMDV challenge.