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Full-length HIV-1 immunogens induce greater magnitude and comparable breadth of T lymphocyte responses to conserved HIV-1 regions compared with conserved-region-only HIV-1 immunogens in rhesus monkeys.

Authors
  • Stephenson, Kathryn E1
  • SanMiguel, Adam
  • Simmons, Nathaniel L
  • Smith, Kaitlin
  • Lewis, Mark G
  • Szinger, James J
  • Korber, Bette
  • Barouch, Dan H
  • 1 Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. , (Israel)
Type
Published Article
Journal
Journal of Virology
Publisher
American Society for Microbiology
Publication Date
Nov 01, 2012
Volume
86
Issue
21
Pages
11434–11440
Identifiers
DOI: 10.1128/JVI.01779-12
PMID: 22896617
Source
Medline
License
Unknown

Abstract

A global HIV-1 vaccine will likely need to induce immune responses against conserved HIV-1 regions to contend with the profound genetic diversity of HIV-1. Here we evaluated the capacity of immunogens consisting of only highly conserved HIV-1 sequences that are aimed at focusing cellular immune responses on these potentially critical regions. We assessed in rhesus monkeys the breadth and magnitude of T lymphocyte responses elicited by adenovirus vectors expressing either full-length HIV-1 Gag/Pol/Env immunogens or concatenated immunogens consisting of only highly conserved HIV-1 sequences. Surprisingly, we found that the full-length immunogens induced comparable breadth (P = 1.0) and greater magnitude (P = 0.01) of CD8(+) T lymphocyte responses against conserved HIV-1 regions compared with the conserved-region-only immunogens. Moreover, the full-length immunogens induced a 5-fold increased total breadth of HIV-1-specific T lymphocyte responses compared with the conserved-region-only immunogens (P = 0.007). These results suggest that full-length HIV-1 immunogens elicit a substantially increased magnitude and breadth of cellular immune responses compared with conserved-region-only HIV-1 immunogens, including greater magnitude and comparable breadth of responses against conserved sequences.

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