Protection of macaques against simian immunodeficiency virus infection with inactivated vaccines: comparison of adjuvants, doses and challenge viruses

Abstract

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 virus 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 required a high dose of antigen and a prolonged immunization schedule. On the day of challenge the titres of antibodies to SIV and to host cell components, as well as the titres of neutralizing antibodies, were significantly higher in the protected animals than in the non-protected. Forty-four vaccinated macaques (of which 36 were protected against previous challenges grown in human cells) and 28 naive animals were then challenged with extracellular or cell-associated SIV grown in simian cells. All naive animals and all vaccinees challenged with extracellular SIV became infected. Four of the eight animals challenged with cell-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 interpreting the results of vaccine trials. This trial has demonstrated that SIV vaccines using different adjuvants can protect macaques against SIV grown in human cells but not against extracellular SIV grown in simian cells. These results have important relevance to the development of HIV vaccines for humans. The results also demonstrate the feasibility and value of large-scale European collaborative experiments in which scarce and ethically sensitive primate resources can be used to evaluate a wide range of vaccine variables.