Antibodies to the putative SIV infection-enhancing domain diminish beneficial effects of an SIV gp160 vaccine in rhesus macaques

W. M. Mitchell, Jose V Torres, P. R. Johnson, V. Hirsch, Tilahun Yilma, M. B. Gardner, W. E. Robinson

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Objective: To demonstrate that antibodies against amino acids (aa) 603-622 of the SIV gp41 transmembrane glycoprotein enhance infection of SIV in vivo. Design: A synthetic peptide derived from aa 603-622 of SIV(mac251) gp41 was synthesized and tested for immunogenicity in rabbits and SIV-infected rhesus macaques. Next, SIV-naive animals were immunized with either a recombinant vaccinia virus expressing the SIV gp160 envelope glycoprotein (VVrgp160) and boosted three times with aa 603-622 (group 1, four animals), wild-type vaccinia virus and boosted with aa 603-622 (group 2, two animals), or VVrgp160 followed by three doses of an irrelevant peptide (group 3, two animals). Animals were challenged with SIV(mac251) Results: Peptide aa 603-622 was immunogenic in rabbits. SIV-infected rhesus monkeys immunized with the peptide developed two-three log increases in antibodies to this peptide and antibodies that could enhance SIV infection in vitro. SIV-naive rhesus macaques in group 1 had higher levels of antibody to the peptide by enzyme-linked immunosorbent assay and higher levels of enhancing antibodies at the time of SIV challenge than the animals in groups 2 or 3. Following challenge with SIV(mac251) the group 1 animals had detectable p27 antigen longer than animals in group 2 and 3 and died of simian AIDS before the respective animals in the two control groups (P<0.05 by log-rank test). Conclusions: aa 603-622 of SIV gp41, like aa 579-613 of HIV gp41, can stimulate production of antibodies that enhance SIV and HIV infection in vitro. Furthermore, immunization with this peptide suppressed beneficial effects of a gp160 vaccine and appeared to enhance SIV infection in vivo.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalAIDS
Volume9
Issue number1
StatePublished - 1995

Keywords

  • AIDS
  • Animal models
  • Antibody-dependent enhancement
  • Complement
  • HIV
  • Pathogenesis
  • SIV
  • Transmembrane glycoprotein
  • Vaccines

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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