Enhancement of Antibodies to the Human Immunodeficiency Virus Type 1 Envelope by Using the Molecular Adjuvant C3d

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Thomas D. Green (Creator)

David C. Montefiori (Creator)

Ted M. Ross (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: DNA vaccines expressing the envelope (Env) protein of the human immunodeficiency virus have been relatively ineffective at generating high-titer long-lasting neutralizing antibodies in a variety of animal models. In this study the murine and human homologues of the complement component C3d were used in a DNA vaccine to enhance the titers of antibody to Env. Initially plasmids expressing a secreted form of Env (sgp120) fused to one two or three copies of the murine homologue of C3d (mC3d) were constructed. Mice were inoculated with four vaccinations of DNA or two DNA vaccinations followed by two boosts of affinitypurified gp120 protein. Analyses of titers demonstrated that multiple copies of mC3d coupled to sgp120 induced long-lasting high-titer anti-Env antibody. Priming mice with sgp120-mC3d-DNA followed by inoculation of purified gp120 protein elicited the strongest antibody titers; however the avidity maturation of the antibody was accelerated in the mice inoculated with sgp120-mC3d3-DNA. In addition DNAs expressing sgp120 fused to three copies of the human homologue of C3d (hC3d3) efficiently enhanced the anti-Env antibody in rabbits. Lastly antisera from both mice and rabbits vaccinated with DNA expressing sgp120-C3d3 elicited higher titers of neutralizing antibody than did nonfused forms of Env. These results indicate that C3d conjugated to sgp120 enhances the antibody responses to Env compared to non-C3d fused forms of Env and this approach may be one way to overcome the poor ability of DNA vaccines to generate antibodies to Env. Originally published Journal of Virology Vol. 77 No. 3 Feb 2003

Additional Information

Publication

Other

Journal of Virology. 77:3(February 2003) p. 2046-2055.

Language: English

Date: 2011

Keywords

DNA vaccines, Human Immunodeficiency Virus envelope, C3d

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