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 S IV in vivo. Design: A synthetic peptide derived from aa 603-622 of SIV mac251 gp41 was synthesized and tested for immunogenicity in rabbits a nd SIV-infected rhesus macaques. Next, SIV-naive animals were immunize d with either a recombinant vaccinia virus expressing the SIV gp160 en velope 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 rabbit s. SIV-infected rhesus monkeys immunized with the peptide developed tw o-three log increases in antibodies to this peptide and antibodies tha t could enhance SIV infection in vitro. SIV-naive rhesus macaques in g roup 1 had higher levels of antibody to the peptide by enzyme-linked i mmunosorbent assay and higher levels of enhancing antibodies at the ti me of SIV challenge than the animals in groups 2 or 3. Following chall enge with SIVmac251 the group 1 animals had detectable p27 antigen lon ger than animals in group 2 and 3 and died of simian AIDS before the r espective 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 bene ficial effects of a gp160 vaccine and appeared to enhance SIV infectio n in vivo.