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Journal of Virology, February 2003, p. 2046-2055, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.2046-2055.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Thomas D. Green,1 David C. Montefiori,2 and Ted M. Ross1*

Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858,1 Center for AIDS Research, Department of Surgery, Duke University Medical Center, Durham, North Carolina 277102

Received 2 July 2002/ Accepted 18 October 2002

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 affinity-purified 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.

* Corresponding author. Mailing address: East Carolina University School of Medicine, Department of Microbiology and Immunology, Brody Health Sciences Building, 600 Moye Blvd., Greenville, NC 27858-4354. Phone: (252) 816-2706. Fax: (252) 816-3104. E-mail: RossT{at}mail.ecu.edu.

Journal of Virology, February 2003, p. 2046-2055, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.2046-2055.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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