INDUCTION OF HUMORAL AND CELLULAR-IMMUNITY TO SIMIAN IMMUNODEFICIENCYVIRUS - WHAT ARE THE REQUIREMENTS FOR PROTECTION

In an effort to produce a strong humoral and cellular immune response that might protect against simian immunodeficiency virus (SIV) infecti on, groups of five rhesus macaques each were immunized intramuscularly at 0, 2 and 6 months with 100 mu g of an inactivated preparation of S IV/Delta(B670) in either an oil-in-water emulsion with Ribi Detox, con taining mycobacterial cell wall skeleton and monophosphoryl lipid A (C WS/MPL) (group A) os a water-in-oil emulsion with incomplete Freund's adjuvant, containing CWS/MPL for the first two injections (group B). A nimals were challenged with 10-100 monkey ID50 of monkey-cell-grown SI V (mac251) 3 months after the last injection, along with a group of fo ur unvaccinated controls. Group B animals demonstrated the strongest i mmune responses following immunization, including neutralizing antibod y titres against the challenge virus ranging from 160 to 320 and SIV-s pecific ELISA titres ranging from 10(5)-10(6) on the day of challenge, as well as strong in vitro lymphoproliferative and interleukin-2 (IL- 2) production responses to the immunogen. Neutralizing antibody was no t detectable in group A animals, ELISA titres were lower (10(2)-10(4)) , no in vitro lymphoproliferative responses were observed, and in vitr o IL-2 production was less pronounced. No protection against challenge was observed in either group. Moreover, group B animals exhibited a m ore pronounced clinical response following challenge than either group A animals or controls, consisting of hyperthermia and a greater degre e of lymphadenopathy on day 7, followed by hypothermia and generally h igher levels of serum viraemia on day 14. Together with other studies, these findings suggest that alternative immunization strategies, usin g non-infectious SIV immunogens, should be explored in an effort to lo ck the immune response to SIV into a cell-mediated mode.