Antibodies to the putative SIV infection-enhancing domain diminish beneficial effects of an SIV gp160 vaccine in rhesus macaques.
OBJECTIVE
To demonstrate that antibodies against amino acids (aa) 603-622 of the SIV gp41 transmembrane glycoprotein enhance infection of SIV in vivo.


METHODS
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.
Mitchell
W M
WM
Department of Pathology, Vanderbilt University, Nashville, Tennessee.
Torres
J
J
Johnson
P R
PR
Hirsch
V
V
Yilma
T
T
Gardner
M B
MB
Robinson
W E
WE
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D015686:Gene Products, env / Q000276:immunology*; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000276:immunology*; D011817:Rabbits; D012191:Retroviridae Proteins / Q000276:immunology*; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D015686:Gene Products, env; D008562:Membrane Glycoproteins; D012191:Retroviridae Proteins; D018449:SAIDS Vaccines; C087575:SIV envelope glycoprotein gp160; C082614:SIV envelope protein gp41; D014759:Viral Envelope Proteins