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

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 SIVmac251 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 SIVmac251.

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 SIVmac251 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.

• Authors: W M Mitchell, J Torres, P R Johnson, V Hirsch, T Yilma, M B Gardner, W E Robinson Jr
• Journal: AIDS (London, England) (AIDS) Vol. 9 Issue 1 Pg. 27-34 (Jan 1995) ISSN: 0269-9370 [Print] England
• PMID: 7893438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Viral
• Gene Products, env
• Membrane Glycoproteins
• Retroviridae Proteins
• SAIDS Vaccines
• SIV envelope glycoprotein gp160
• SIV envelope protein gp41
• Viral Envelope Proteins

Topics

• Animals
• Antibodies, Viral (immunology)
• Dose-Response Relationship, Immunologic
• Gene Products, env (immunology)
• Macaca mulatta
• Membrane Glycoproteins (immunology)
• Rabbits
• Retroviridae Proteins (immunology)
• SAIDS Vaccines (immunology)
• Simian Acquired Immunodeficiency Syndrome (immunology)
• Simian Immunodeficiency Virus (immunology)
• Viral Envelope Proteins (immunology)