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. Dona-Rose, G. H. Learn, A. G. Rodrigo, D. C. Nickle, F. Li, M. Mahalanabis, M. T. Hensel, S. McLaughlin, P. F. Edmonson, D. Montefiori, S. W. Barnett, Nancy Haigwood, J. I. Mullins

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11214-11224
Number of pages11
JournalJournal of Virology
Volume79
Issue number17
DOIs
StatePublished - Sep 2005
Externally publishedYes

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Human immunodeficiency virus 1
Neutralizing Antibodies
neutralizing antibodies
HIV-1
rabbits
Rabbits
env Genes
Proteins
Vaccines
proteins
neutralization
ancestry
vaccines
Viruses
Synthetic Genes
synthetic genes
Cercopithecine Herpesvirus 1
viruses
genes
immunoglobulin G

ASJC Scopus subject areas

  • Immunology

Cite this

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. / Dona-Rose, N. A.; Learn, G. H.; Rodrigo, A. G.; Nickle, D. C.; Li, F.; Mahalanabis, M.; Hensel, M. T.; McLaughlin, S.; Edmonson, P. F.; Montefiori, D.; Barnett, S. W.; Haigwood, Nancy; Mullins, J. I.

In: Journal of Virology, Vol. 79, No. 17, 09.2005, p. 11214-11224.

Research output: Contribution to journalArticle

Dona-Rose, NA, Learn, GH, Rodrigo, AG, Nickle, DC, Li, F, Mahalanabis, M, Hensel, MT, McLaughlin, S, Edmonson, PF, Montefiori, D, Barnett, SW, Haigwood, N & Mullins, JI 2005, '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', Journal of Virology, vol. 79, no. 17, pp. 11214-11224. https://doi.org/10.1128/JVI.79.17.11214-11224.2005
Dona-Rose, N. A. ; Learn, G. H. ; Rodrigo, A. G. ; Nickle, D. C. ; Li, F. ; Mahalanabis, M. ; Hensel, M. T. ; McLaughlin, S. ; Edmonson, P. F. ; Montefiori, D. ; Barnett, S. W. ; Haigwood, Nancy ; 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. In: Journal of Virology. 2005 ; Vol. 79, No. 17. pp. 11214-11224.
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