VACCINE EVALUATION STUDIES OF REPLICATION-DEFECTIVE SIV SMB7

Non-infectious virus-like particles of SIVsmB7 that expresses env and gag gene products but are defective in pol and vpx/vpr were assessed f or their ability to induce protective immunity against infection with pathogenic SIVsmE660 in rhesus macaques. Animals were immunized in thr ee groups: group A was primed with cell-associated SIVsmB7 and boosted with cell-free SIVsmB7; group B was primed with cell-free SIVsmB7 and boosted with cell-free SIVsmB7 conjugated to iron oxide microbeads; g roup C was primed with cell-free SIVsmB7 mixed with Titer Max adjuvant and boosted with cell-free SIVsmB7 mixed with SAF-M adjuvant followed by secondary boosting with cell-free SIVsmB7 conjugated to microbeads . Animals were challenged intravenously with 20 animal infectious dose s of SIVsmE660 grown in rhesus peripheral blood mononuclear cells 3 we eks after final boosting. All animals became infected as evidenced by quantitative virus cultivation. Sera from immunized animals contained low-titer antibodies by ELISA and low or undetectable neutralizing ant ibodies on the day of challenge but strong anamnestic antibody respons es were observed following challenge. Interestingly, 2 of 3 animals in group A showed evidence of transient viremia and more stable CD4 coun ts following challenge as compared to the other immunized animals and to non-immunized controls. Thus, immunization with cell-associated SIV smB7 did not provide sterilizing immunity against challenge with a hig hly pathogenic SIV strain but might have caused virus clearance later in infection.