In vitro spontaneous production of anti-SIV antibodies is a reliable tool in the follow-up of protection of SIV-vaccinated monkeys

To assess the reliability of the spontaneous in vitro synthesis of simian immunodeficiency virus (SIV)-specific antibodies as a marker in the monitoring of protection in SIV-vaccinated animals, Macaca fascicularis monkeys were immunized with formalin-inactivated SIV(mac)251 or SIV(mac)251/32H, and challenged with human-derived (SIV(mac)251/32H) or monkey-derived live SIV. As judged by virus isolation and polymerase chain reaction (PCR) techniques, immunized animals were protected against human- derived SIV challenge, and no spontaneous in vitro synthesis of anti-SIV antibody was observed in nonstimulated peripheral blood mononuclear cell cultures over a 4-month follow-up. On the contrary, human cell-grown SIV(mac)251 immunization did not afford protection against monkey-derived SIV, and all the animals became infected and showed spontaneous in vitro synthesis of anti-SIV antibodies. These data demonstrate that lack of protection in SIV-vaccinated monkeys is strictly associated with PBMC ability of spontaneously produce anti-SIV antibodies in vitro following challenge, and suggest that this parameter might also constitute a reliable marker for monitoring protection in large-scale HIV vaccination and immunotherapy programs.