AIDS Vaccine Development: the Past, the Present, and the Future

AIDS was first reported in 1981 by Gottlieb MS et al at USC (University of California) Medical Center: Healthy homosexual men with pneumocystis carinii pneumonia and mucosal can-didiasis had deficiency in CD4 T lymphocyte, a critical immune defense cell (1). In 1983, Dr. F. Barré-Sinoussi and L. Montagnier isolated a new human T-lymphotropic retrovirus, later named HIV-1(human immunodeficiency virus type 1) which turned out to be one of the causes of AIDS (2). Through their discovery, they received the 2008 Nobel Prize in Physiology or Medicine award. Discovery of the causative agent of AIDS had been the driving force to investigate its genomic structure, function, and replication mechanism. Most importantly, the development of a diagnostic kit contributed to the knowledge of AIDS as an infectious disease especially in the route of transmission. In addition, the development of antiretroviral drugs reduced the mortality of some HIV-infected individuals. However, high price and side effects of the current therapeutic drugs have not been beneficial for most AIDS patients. Thus, it has been generally accepted that the development of a low price and effective prophylactic AIDS vaccine is the only answer to stop the global epidemic. Despite tremendous efforts over the past 25 years, there is no promising candidate for an HIV vaccine. No one has even been able to design and develop a model leading to an effective vaccine. This review will introduce four major milestones in AIDS vaccine development to date which resulted in major social, economic and scientific impacts (Fig. 1). In 1989, the hopes for a HIV vaccine started from a highly effective formalin-inactivated whole SIV vaccine which was known to confer protection in macaques with AIDS (3). However, three years later, it was found that the protective effect was mediated by antigens (such as HLA and β2m) from the human cells used to grow the viral strain (4). In 1992, Dr. Ronald Desrosiers reported that a live attenuated SIV vaccine with a deletion in the nef gene can be efficient in treating AIDS of macaques (5). Unfortunately, three years later, Dr. Ruth Ruprecht found that this live attenuated vaccine had a safety issue in which the vaccine itself caused AIDS in neonatal macaques. For this reason, research into the development of a live attenuated vaccine has been no longer carried out (6). In 1990, Genentech reported that their recombinant glyco-protein gp120 subunit vaccine could induce protection in chimpanzees with …