A 30-year journey of trial and error towards a tolerogenic AIDS vaccine.

Since 1985, we have tested several immunological approaches to suppressing HIV replication in HIV-infected patients and to prevent HIV acquisition in uninfected people. Here, after briefly reviewing our studies on immunosuppressive treatments and therapeutic dendritic cell-based therapies, we examine in more detail our work on the tolerogenic vaccines we developed against AIDS in Chinese macaques. The vaccine consisted of inactivated SIVmac239 particles adjuvanted with the Bacillus of Calmette and Guerin (BCG), Lactobacillus plantarum (LP), or Lactobacillus rhamnosus (LR). Without adjuvant, the vaccine administered by the intragastric route induced the usual simian immunodeficiency virus (SIV)-specific humoral immune responses but no post-challenge protection. In contrast, out of 24 macaques that were immunized with the adjuvanted vaccine and challenged intrarectally with SIVmac239 or SIVB670, 23 were sterilely protected for up to 5 years, while all control macaques were infected. On the other hand, all macaques of Indian origin that were immunized with the same adjuvanted vaccine were not protected. We then discovered that vaccinated Chinese macaques developed a previously unrecognized class of non-cytolytic MHC-Ib/E-restricted CD8