Session 48Poster Presentations Vaccine Adjuvants Session Day and Time: Tuesday 1:30 - 3:30 pm Room: Hall D
400 Enhancement of Immune Responses to HIV-1 by DNA Vaccination Using the Complement Protein, C3d T. Ross*1, T. Green1, J. Sodroski2, J. Bower1 1East Carolina Univ, Sch of Med, Greenville, NC and 2Dana-Farber Cancer Inst, Boston, MA
Background: A central problem for the development of DNA vaccines has been to identify immunogens capable of raising high titer, long lasting, neutralizing antibody to surface viral glycoproteins. HIV-1 envelope (Env) has proven to be a weak immunogen, raising low titer antibodies that are slow to undergo affinity maturation. DNA immunogens were used to test the C3d component of complement as a molecular adjuvant for Env.
Methods: To test a potential adjuvant role of C3d for Env, DNA constructs were produced encoding soluble forms of wild-type or codon-optimized monomers (sgp120) or oligomers (sgp140) of Env fused to the murine or human homologues of C3d and used for immunizations in mice or rabbits. DNA vaccine plasmids encoding secreted forms of each antigen and these same forms fused at the carboxyl terminus to various copies of C3d were compared for immunogenicity.
Results: Raised antibody from DNA expressing Env-C3d showed statistically enhanced titers for Env-specific IgG (103- to 105-fold increase) compared to DNA expressing Env only. C3d fusions increased the immunogenicity of Env by increasing the efficiency of the initiation of anti-Env Ab response and by increasing the ability of antibodies to undergo affinity maturation. In addition, neutralizing antibodies against viral infection were protective in mice vaccinated with DNA expressing C3d fused to Env. However, no enhancement of germinal center formation has been observed.
Conclusions: C3d is a potent molecular adjuvant capable of raising long-lasting neutralizing antibodies to HIV-1 Env. C3d coupled antigens enhance the humoral immune response, alter cytokine profiles, and stimulate T-helper responses. C3d has great potential for boosting the immunity to both infectious disease antigens, including biodefense agents, as well as non-infectious, tumor antigens.
