PROTECTION OF MACAQUES AGAINST SIMIAN IMMUNODEFICIENCY VIRUS-INFECTION WITH INACTIVATED VACCINES - COMPARISON OF ADJUVANTS, DOSES AND CHALLENGE VIRUSES

Nine European laboratories contributed a total of 98 macaques towards a collaborative trial to study the ability of formaldehyde-inactivated or subunit SIV vaccines to protect immunized animals against live vir us challenges. Four adjuvants, three dose levels and two immunization schedules were compared. Fifty-two of 61 (85%) immunized animals were protected against infection after challenge with either homologous or heterologous virus strains grown in human cells. Optimum protection re quired a high dose of antigen and a prolonged immunization schedule. O n the clay of challenge the titres of antibodies to SIV and to host ce ll components, as well as the titres of neutralizing antibodies, were significantly, higher in the protected animals than in the non-protect ed. Forty-four vaccinated macaques (of which 36 were protected against previous challenges grown in human cells) and 28 naive animals were t hen challenged with extracellular or cell-associated SIV grown in simi an cells. All naive animals and all vaccinees challenged with extracel lular SIV became infected. Foul of the eight animals challenged with c ell-associated viruses were protected. These results clearly indicate that vaccines which potently protect against SIV grown in human cells, do not protect against SIV grown in simian cells. The cell substrate on which challenge viruses are grown is clearly significant in interpr eting the results of vaccine trials. This trial has demonstrated that SIV vaccines using different adjuvants can protect macaques against SI V grown in human cells but nor against extracellular SIV gl own in sim ian cells. These results have important relevance to the development o f HIV vaccines for humans. The results also demonstrate feasibility an d value of large-scale European collaborative experiments in which sca rce and ethically sensitive primate resources can be used to evaluate a wide range of vaccine variables.