This Article Full Text Full Text (PDF) 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 Doria-Rose, N. A. Articles by Mullins, J. I. Search for Related Content PubMed PubMed Citation Articles by Doria-Rose, N. A. Articles by Mullins, J. I.

Human Immunodeficiency Virus Type 1 Subtype B Ancestral Envelope Protein Is Functional and Elicits Neutralizing Antibodies in Rabbits Similar to Those Elicited by a Circulating Subtype B Envelope

N. A. Doria-Rose,^1,2,3, G. H. Learn,^2, A. G. Rodrigo,^2,, D. C. Nickle,² F. Li,^2,¶ M. Mahalanabis,^1,2 M. T. Hensel,³ S. McLaughlin,² P. F. Edmonson,^4,|| D. Montefiori,⁶ S. W. Barnett,⁷ N. L. Haigwood,^1,2,3 and J. I. Mullins^2,4,5*

Seattle Biomedical Research Institute, Seattle, Washington,¹ Departments of Microbiology,² Pathobiology,³ Laboratory Medicine,⁴ Medicine, University of Washington, Seattle, Washington,⁵ Duke University, Durham, North Carolina,⁶ Chiron Corporation, Emeryville, California⁷

Received 21 March 2005/ Accepted 7 June 2005

Human immunodeficiency virus type 1 (HIV-1) is a difficult target for vaccine development, in part because of its ever-expanding genetic diversity and attendant capacity to escape immunologic recognition. Vaccine efficacy might be improved by maximizing immunogen antigenic similarity to viruses likely to be encountered by vaccinees. To this end, we designed a prototype HIV-1 envelope vaccine using a deduced ancestral state for the env gene. The ancestral state reconstruction method was shown to be >95% accurate by computer simulation and 99.8% accurate when estimating the known inoculum used in an experimental infection study in rhesus macaques. Furthermore, the deduced ancestor gene differed from the set of sequences used to derive the ancestor by an average of 12.3%, while these latter sequences were an average of 17.3% different from each other. A full-length ancestral subtype B HIV-1 env gene was constructed and shown to produce a glycoprotein of 160 kDa that bound and fused with cells expressing the HIV-1 coreceptor CCR5. This Env was also functional in a virus pseudotype assay. When either gp160- or gp140-expressing plasmids and recombinant gp120 were used to immunize rabbits in a DNA prime-protein boost regimen, the artificial gene induced immunoglobulin G antibodies capable of weakly neutralizing heterologous primary HIV-1 strains. The results were similar for rabbits immunized in parallel with a natural isolate, HIV-1 SF162. Further design efforts to better present conserved neutralization determinants are warranted.

N.A.D.-R., G.H.L., and A.G.R. contributed equally to the work.

Present address: University of Auckland, New Zealand.

^¶ Present address: Northwest Hospital and Medical Center, Seattle, Wash.

^|| Present address: Fred Hutchinson Cancer Research Center, Seattle, Wash.

This article has been cited by other articles:

• Moir, S., Ho, J., Malaspina, A., Wang, W., DiPoto, A. C., O'Shea, M. A., Roby, G., Kottilil, S., Arthos, J., Proschan, M. A., Chun, T.-W., Fauci, A. S. (2008). Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J. Exp. Med. 0: jem.20072683-9 [Abstract] [Full Text]  
• Kraft, Z., Strouss, K., Sutton, W. F., Cleveland, B., Tso, F. Y., Polacino, P., Overbaugh, J., Hu, S.-L., Stamatatos, L. (2008). Characterization of Neutralizing Antibody Responses Elicited by Clade A Envelope Immunogens Derived from Early Transmitted Viruses. J. Virol. 82: 5912-5921 [Abstract] [Full Text]  
• Ching, L. K., Vlachogiannis, G., Bosch, K. A., Stamatatos, L. (2008). The First Hypervariable Region of the gp120 Env Glycoprotein Defines the Neutralizing Susceptibility of Heterologous Human Immunodeficiency Virus Type 1 Isolates to Neutralizing Antibodies Elicited by the SF162gp140 Immunogen. J. Virol. 82: 949-956 [Abstract] [Full Text]  
• Buonaguro, L., Tornesello, M. L., Buonaguro, F. M. (2007). Human Immunodeficiency Virus Type 1 Subtype Distribution in the Worldwide Epidemic: Pathogenetic and Therapeutic Implications. J. Virol. 81: 10209-10219 [Full Text]  
• Rolland, M., Jensen, M. A., Nickle, D. C., Yan, J., Learn, G. H., Heath, L., Weiner, D., Mullins, J. I. (2007). Reconstruction and Function of Ancestral Center-of-Tree Human Immunodeficiency Virus Type 1 Proteins. J. Virol. 81: 8507-8514 [Abstract] [Full Text]  
• Liu, Y., McNevin, J., Cao, J., Zhao, H., Genowati, I., Wong, K., McLaughlin, S., McSweyn, M. D., Diem, K., Stevens, C. E., Maenza, J., He, H., Nickle, D. C., Shriner, D., Holte, S. E., Collier, A. C., Corey, L., McElrath, M. J., Mullins, J. I. (2006). Selection on the Human Immunodeficiency Virus Type 1 Proteome following Primary Infection. J. Virol. 80: 9519-9529 [Abstract] [Full Text]  
• Derby, N. R., Kraft, Z., Kan, E., Crooks, E. T., Barnett, S. W., Srivastava, I. K., Binley, J. M., Stamatatos, L. (2006). Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection.. J. Virol. 80: 8745-8762 [Abstract] [Full Text]  
• Weaver, E. A., Lu, Z., Camacho, Z. T., Moukdar, F., Liao, H.-X., Ma, B.-J., Muldoon, M., Theiler, J., Nabel, G. J., Letvin, N. L., Korber, B. T., Hahn, B. H., Haynes, B. F., Gao, F. (2006). Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen. J. Virol. 80: 6745-6756 [Abstract] [Full Text]  
• Madkan, V. K., Giancola, A. A., Sra, K. K., Tyring, S. K. (2006). Sex differences in the transmission, prevention, and disease manifestations of sexually transmitted diseases.. Arch Dermatol 142: 365-370 [Abstract] [Full Text]