MaRGA Meeting, 2004: Abstracts

18: Physiology and Immunology

Immunogenicity of GBV-B DNA Vaccines in Common Marmosets

S. Biswas¹, Keith Mansfield², James Jacob³ and Shan Lu¹

Affiliation: ¹Department of Medicine, University of Massachusetts Medical School, Worcester, MA; ²New England Regional Primate Research Center, Harvard, Medical School, Southborough, MA; and ³College of Veterinary Medicine, Cornell University, Ithaca, NY

The common marmoset, Callithrix jacchus, an important animal model potentially represents an alternative species to more traditional nonhuman primates. A major impediment in the study of Hepatitis C virus (HCV) is the lack of affordable yet relevant animal models. GB virus-B (GBV-B), which infects and causes hepatitis in marmosets, has been described to be phylogenetically most closely related to HCV. We have developed the common marmosets as a relevant animal model for HCV vaccine development studies and also to generate and identify useful immunological tools and reagents that will be used for further research involving this animal model. The envelope proteins of HCV are likely vaccine candidates and their counterparts in GBV-B, E1 and E2, were examined for their immunogenicity in marmosets. The genes coding for GBV-B envelope proteins were cloned in a mammalian expression vector and used to immunize marmosets via gene gun methodology. It was evident that DNA immunization with the DNA vaccine expressing only GBV-B E2 antigen and not where E1 was expressed in cis, generated high levels of E2-specific antibodies as demonstrated by ELISA and Western blot analysis of the marmoset sera, using antihuman antibodies as the secondary antibody. The effect of DNA priming was further demonstrated when the immunized animals showed enhanced anti-E2 antibody responses (anamnestic) after being challenged with GBV-B while there was no detectable anti-E2 antibody in na•ve animals shortly after viral challenge. Thus, we describe for the first time the generation of a specific immune response mediated by DNA immunization in the common marmosets. We confirm the cross-reactivity of antihuman IgG to marmoset antibodies as observed in other studies and our research further opens the door for studies of many such reagents in the future.