STRATEGIES FOR AIDS VACCINES

In the global AIDS epidemic, over half of all infections have occurred in people less than 25 years old resulting in profound social, econom ic and demographic consequences. Current estimates indicate that the p resent 15 million HIV infections will increase to over 30 million by t he end of the millennium. For most countries a safe and effective vacc ine offers the only hope of controlling the spread of this disease. Th e development of an effective vaccine against HIV is beset with formid able obstacles. Despite these difficulties, substantial progress has b een made towards developing effective strategies for vaccination. Huma n clinical trials and animal models for AIDS, particularly simian immu nodeficiency virus (SIV) infection of macaques, have proved invaluable in this quest. Inactivated virus vaccines induced potent protection i n this model, but subsequent studies revealed that protection was medi ated by antibody to cellular proteins present in the vaccine preparati ons and on the surface of infecting virions. This surprising observati on has provided an alternative and complementary approach to the devel opment of vaccines against HIV in man which is still being pursued. Li ve attenuated vaccines were initially dismissed as far too hazardous. However, the concept has recently been reexamined in the light of powe rful evidence that attenuated SIV induces potent protection against a wide variety of viruses administered by intravenous or mucosal routes and even against challenge with viable virus-infected spleen cells. Ef forts are now underway to understand the mechanism of this protection and to attempt to reproduce it by less hazardous means. Considerable e ffort has been devoted to the development of subunit HIV vaccines, pre dominantly based on the envelope glycoproteins of the virus. Extensive clinical trials in human volunteers have established that these vacci nes are safe and antigenic. However, the immune responses appear to be transient and the antibodies induced do not neutralize the primary is olates of HIV which are circulating in the population. There are now t hree possible approaches to an AIDS vaccine which are being actively p ursued.