Development of DNA vaccines for foot-and-mouth disease, evaluation of vaccines encoding replicating and non-replicating nucleic acids in swine

• Published in: Journal of biotechnology Vol. 73; no. 2; pp. 243 - 249
• Main Authors: Beard, C, Ward, G, Rieder, E, Chinsangaram, J, Grubman, M.J, Mason, P.W
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Lausanne Elsevier B.V 20-08-1999; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Antibodies; Aphthovirus - genetics; Aphthovirus - immunology; Aphthovirus - physiology; Attenuated virus; Biological and medical sciences; Biotechnology; Cells; Diseases; DNA; Empty capsids; Enzymes; Foot-and-Mouth Disease - immunology; Foot-and-Mouth Disease - prevention & control; Foot-and-Mouth Disease - virology; Foot-and-mouth disease virus; Fundamental and applied biological sciences. Psychology; Genes; Health. Pharmaceutical industry; Humans; Industrial applications and implications. Economical aspects; Mice; Nucleic acid vaccine; Production of active biomolecules; Proteins; RNA; Swine; Swine Diseases - immunology; Swine Diseases - prevention & control; Swine Diseases - virology; Vaccine; Vaccines, DNA - genetics; Vaccines, DNA - pharmacology; Vaccins; Viral Vaccines - genetics; Viral Vaccines - pharmacology; Virus Replication - genetics; Viruses; Nucleic acid vaccine; Empty capsids; Attenuated virus; Foot-and-mouth disease virus; Vaccine; Infection; Virus; Aphthovirus; Foot and mouth disease; Picornaviridae; Viral disease; Pathogenic; Domestic animal; Attenuated strain; Genetic vaccine
• ISSN: 0168-1656; 1873-4863
• DOI: 10.1016/S0168-1656(99)00142-X

We have developed naked DNA vaccine candidates for foot-and-mouth disease (FMD), an important disease of domestic animals. The virus that causes this disease, FMDV, is a member of the picornavirus family, which includes many important human pathogens, such as poliovirus, hepatitis A virus, and rhinovirus. Picornaviruses are characterized by a small (7–9000 nucleotide) RNA genome that encodes capsid proteins, processing proteinases, and enzymes required for RNA replication. We have developed two different types of DNA vaccines for FMD. The first DNA vaccine, pP12X3C, encodes the viral capsid gene (P1) and the processing proteinase (3C). Cells transfected with this DNA produce processed viral antigen, and animals inoculated with this DNA using a gene gun produced detectable antiviral immune responses. Mouse inoculations with this plasmid, and with a derivative containing a mutation in the 3C proteinase, indicated that capsid assembly was essential for induction of neutralizing antibody responses. The second DNA vaccine candidate, pWRMHX, encodes the entire FMDV genome, including the RNA-dependent RNA polymerase, permitting the plasmid-encoded viral genomes to undergo amplification in susceptible cells. pWRMHX encodes a mutation at the cell binding site, preventing the replicated genomes from causing disease. Swine inoculated with this vaccine candidate produce viral particles lacking the cell binding site, and neutralizing antibodies that recognize the virus. Comparison of the immune responses elicited by pP12X3C and pWRMHX in swine indicate that the plasmid encoding the replicating genome stimulated a stronger immune response, and swine inoculated with pWRMHX by the intramuscular, intradermal, or gene gun routes were partially protected from a highly virulent FMD challenge.