Therapeutic vaccination for chronic infectious diseases: Lessons from HIV-1

Most therapeutic vaccines are usually divided into two groups according to their mode of action on immunity, based on the induction of either a humoral response (antibodies) or a cellular response, mostly cytotoxic T lymphocytes (CTLs). The latter ones are in fact the most promising candidates for the treatment of cancer and chronic viral infections. However, we must admit that the design of such vaccines is far from being simple as the biology of the chronic infectious diseases involves complex issues such as viral latency, the existence of reservoirs or immune escape mechanisms. Furthermore, the concept of therapeutic vaccination implies that the host immune system is still competent for eliciting an immune response after vaccination, but patients suffering from chronic infectious diseases usually exhibit impaired immune defenses. To overcome this challenge, the actual tendency is to combine chemotherapy and therapeutic vaccination, playing around with schedules of vaccine administration and standard chemotherapy. To illustrate the different steps in the design and testing of a therapeutic vaccine, the human immunodeficiency virus (HIV-1) for which the efficacy of therapeutic vaccines is currently being evaluated, could serve as a model. Specific points like the rationale of using HIV-1 regulatory genes instead of structural genes, the possibility of using multiple injections of vaccine candidates or the importance of pre-existing immunity will be emphasized, together with the risks of inducing the emergence of new HIV-1 variants upon vaccine treatment of chronically infected HIV-1 patients. The current expertise in the field of therapeutic vaccines in chronically infected HIV-1 patients could be of interest for the design of a therapeutic vaccine for HBV infection. (C) 2005 Elsevier B.V. All rights reserved.