This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vaine, M. Articles by Lu, S. Search for Related Content PubMed PubMed Citation Articles by Vaine, M. Articles by Lu, S.

 Previous Article  |  Next Article 

Journal of Virology, August 2008, p. 7369-7378, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00562-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Improved Induction of Antibodies against Key Neutralizing Epitopes by Human Immunodeficiency Virus Type 1 gp120 DNA Prime-Protein Boost Vaccination Compared to gp120 Protein-Only Vaccination ^,

Michael Vaine,¹ Shixia Wang,¹ Emma T. Crooks,² Pengfei Jiang,² David C. Montefiori,³ James Binley,² and Shan Lu^1*

Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655,¹ Torrey Pines Institute for Molecular Studies, San Diego, California 92121,² Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710³

Received 13 March 2008/ Accepted 12 May 2008

A major challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development is to elicit potent and broadly neutralizing antibodies that are effective against primary viral isolates. Previously, we showed that DNA prime-protein boost vaccination using HIV-1 gp120 antigens was more effective in eliciting neutralizing antibodies against primary HIV-1 isolates than was a recombinant gp120 protein-only vaccination approach. In the current study, we analyzed the difference in antibody specificities in rabbit sera elicited by these two immunization regimens using peptide enzyme-linked immunosorbent assay and a competitive virus capture assay. Our results indicate that a DNA prime-protein boost regimen is more effective than a protein-alone vaccination approach in inducing antibodies that target two key neutralizing domains: the V3 loop and the CD4 binding site. In particular, positive antibodies targeting several peptides that overlap with the known CD4 binding area were detected only in DNA-primed sera. Different profiles of antibody specificities provide insight into the mechanisms behind the elicitation of better neutralizing antibodies with the DNA prime-protein boost approach, and our results support the use of this approach to further optimize Env formulations for HIV vaccine development.

---

* Corresponding author. Mailing address: Room 304, LRB, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Lazare Research Building, Worcester, MA 01605. Phone: (508) 856-6791. Fax: (508) 856-6751. E-mail: shan.lu{at}umassmed.edu

Published ahead of print on 21 May 2008.

Supplemental material for this article may be found at http://jvi.asm.org/.

---

Journal of Virology, August 2008, p. 7369-7378, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00562-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Binley, J. M., Lybarger, E. A., Crooks, E. T., Seaman, M. S., Gray, E., Davis, K. L., Decker, J. M., Wycuff, D., Harris, L., Hawkins, N., Wood, B., Nathe, C., Richman, D., Tomaras, G. D., Bibollet-Ruche, F., Robinson, J. E., Morris, L., Shaw, G. M., Montefiori, D. C., Mascola, J. R. (2008). Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C. J. Virol. 82: 11651-11668 [Abstract] [Full Text]