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181 Enhanced Humoral Immune Responses Elicited by DNA Vaccination with HIV gp120-C3d Fusion Constructs
T. Ross*1, T. Green1, Y. Xu2, D. Montefiori3, and H. Robinson2
1East Carolina Univ., Greenville, NC, USA; 2Emory Univ., Atlanta, GA, USA; and 3Duke Univ., Durham, NC, USA
Background: A central problem for the development of HIV-1 vaccines has been to identify immunogens capable of raising high titer, long lasting, neutralizing antibody to the envelope glycoproteins (Envs) of primary isolates. The HIV-1 Env has proven to be a weak immunogen, raising low titer antibodies that are slow to undergo affinity maturation.
Methods: DNA immunogens were used to test the C3d component of complement as a molecular adjuvant for Env. To test a potential adjuvant role of C3d for Env, DNA constructs were produced encoding Env fused to C3d and used for immunizations.
Results: Expression of plasmid constructs in vitro showed that these constructs were efficiently secreted from cells. Vaccine plasmids encoding secreted monomeric (gp120) forms of a primary Env and these same forms of Env fused at the carboxyl terminus to 3 tandem copies of C3d were compared for immunogenicity in mice using DNA immunization. Raised antibody showed increased titers for the levels of Env-specific IgG and enhanced maturation of the antibody response.
Conclusions: C3d fusions increased the immunogenicity of Env both by increasing the efficiency of the initiation of anti-Env Ab response and by increasing the ability of anti-Env Ab to undergo affinity maturation.
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