MATURATION OF IMMUNE-RESPONSES TO LENTIVIRUS INFECTION - IMPLICATIONSFOR AIDS VACCINE DEVELOPMENT

The evaluation of attenuated vaccines in the simian immunodeficiency v irus and equine infectious anemia virus animal models has demonstrated the ability of this immunization strategy to elicit broad and endurin g immune protection from virus exposure. The development of protective immunity by these attenuated virus vaccines, however, has been shown to be time dependent and to be associated with a complex and lengthy m aturation of immune responses over the first 6 to 8 months postinocula tion, During this time period, envelope-specific antibody responses un dergo an evolution in quantitative and qualitative properties that is similar, but distinct for each lentivirus system. The completed matura tion of immune responses is then characterized by relatively steady-st ate antibody responses that are maintained indefinitely. The accomplis hment of optimum vaccine protection is associated with achievement of a fully mature immune response, whereas nonprotective or enhancing vac cine immunity appears to be associated with immature immune responses elicited by ineffective vaccines, These observations indicate that the development of an effective acquired immunodeficiency syndrome (AIDS) vaccine will require immunization strategies that can achieve the nec essary maturation of immune responses to human immunodeficiency virus type 1 (HIV-1) antigens in the minimum amount of time. Therefore, AIDS vaccine strategies based on attenuated live virus vaccines or on DNA immunization procedures, perhaps in conjunction with cytokine or secon dary costimulatory molecules to accelerate immune maturation, may be b est suited to accomplish the goal of an effective and practical AIDS v accine for worldwide use.