Skip to main content
Journal cover image

A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys.

Publication ,  Journal Article
Santra, S; Korber, BT; Muldoon, M; Barouch, DH; Nabel, GJ; Gao, F; Hahn, BH; Haynes, BF; Letvin, NL
Published in: Proc Natl Acad Sci U S A
July 29, 2008

One of the major challenges that must be met in developing an HIV-1 vaccine is devising a strategy to generate cellular immunity with sufficient breadth to deal with the extraordinary genetic diversity of the virus. Amino acids in the envelopes of viruses from the same clade can differ by >15%, and those from different clades can differ by >30%. It has been proposed that creating immunogens using centralized HIV-1 gene sequences might provide a practical solution to this problem. Such centralized genes can be generated by employing a number of different strategies: consensus, ancestral, or center of tree sequences. These computer-generated sequences are a shorter genetic distance from any two contemporary virus sequences than those contemporary sequences are from each other. The present study was initiated to evaluate the breadth of cellular immunity generated through immunization of rhesus monkeys with vaccine constructs expressing either an HIV-1 global consensus envelope sequence (CON-S) or a single patient isolate clade B envelope sequence (clade B). We show that vaccine immunogens expressing the single centralized gene CON-S generated cellular immune responses with significantly increased breadth compared with immunogens expressing a wild-type virus gene. In fact, CON-S immunogens elicited cellular immune responses to 3- to 4-fold more discrete epitopes of the envelope proteins from clades A, C, and G than did clade B immunogens. These findings suggest that immunization with centralized genes is a promising vaccine strategy for developing a global vaccine for HIV-1 as well as vaccines for other genetically diverse viruses.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

July 29, 2008

Volume

105

Issue

30

Start / End Page

10489 / 10494

Location

United States

Related Subject Headings

  • Vaccines, DNA
  • Regression Analysis
  • Plasmids
  • Macaca mulatta
  • Interferon-gamma
  • Immune System
  • Humans
  • HIV-1
  • Gene Products, env
  • Gene Expression Regulation, Viral
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Santra, S., Korber, B. T., Muldoon, M., Barouch, D. H., Nabel, G. J., Gao, F., … Letvin, N. L. (2008). A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys. Proc Natl Acad Sci U S A, 105(30), 10489–10494. https://doi.org/10.1073/pnas.0803352105
Santra, Sampa, Bette T. Korber, Mark Muldoon, Dan H. Barouch, Gary J. Nabel, Feng Gao, Beatrice H. Hahn, Barton F. Haynes, and Norman L. Letvin. “A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys.Proc Natl Acad Sci U S A 105, no. 30 (July 29, 2008): 10489–94. https://doi.org/10.1073/pnas.0803352105.
Santra S, Korber BT, Muldoon M, Barouch DH, Nabel GJ, Gao F, et al. A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10489–94.
Santra, Sampa, et al. “A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys.Proc Natl Acad Sci U S A, vol. 105, no. 30, July 2008, pp. 10489–94. Pubmed, doi:10.1073/pnas.0803352105.
Santra S, Korber BT, Muldoon M, Barouch DH, Nabel GJ, Gao F, Hahn BH, Haynes BF, Letvin NL. A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10489–10494.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

July 29, 2008

Volume

105

Issue

30

Start / End Page

10489 / 10494

Location

United States

Related Subject Headings

  • Vaccines, DNA
  • Regression Analysis
  • Plasmids
  • Macaca mulatta
  • Interferon-gamma
  • Immune System
  • Humans
  • HIV-1
  • Gene Products, env
  • Gene Expression Regulation, Viral