Scientific Publications by FDA Staff

PLoS One 2020 Mar 4;15(3):e0228163

Immunotherapy with DNA vaccine and live attenuated rubella/SIV gag vectors plus early ART can prevent SIVmac251 viral rebound in acutely infected rhesus macaques.

Virnik K, Rosati M, Medvedev A, Scanlan A, Walsh G, Dayton F, Broderick KE, Lewis M, Bryson Y, Lifson JD, Ruprecht RM, Felber BK, Berkower I

Anti-retroviral therapy (ART) has been highly successful in controlling HIV replication, reducing viral burden, and preventing progression to AIDS. But ART alone cannot cure the infection. Even after years of successful therapy, ART withdrawal leads inevitably to viral rebound within a few weeks or months. Our hypothesis: effective therapy must control both the replicating pool and the latent viral reservoir. To do this, we have combined ART and immunotherapy to attack both viral pools simultaneously. The vaccine regimen consisted of DNA vaccine expressing SIV Gag, followed by a boost with live attenuated rubella/gag vectors. The vectors grow well in rhesus macaques, and they are potent immunogens when used in a prime and boost strategy. We infected rhesus macaques by high dose mucosal challenge with virulent SIVmac251 and waited three days to seed the viral reservoir before starting ART. The control group received control DNA and empty rubella vaccine. The vaccine group received immunotherapy with DNA/gag prime, followed by rubella vectors expressing SIV gag, while on ART. Both groups had a vaccine “take” to rubella, and the vaccine group developed antibodies and T cells specific for Gag. Five weeks after the last immunization, we stopped ART and monitored virus rebound. All four control animals eventually had a viral rebound, and two were euthanized for AIDS-like illness. Remarkably, one control macaque did not rebound after ART release, or CD8 depletion, yet, he did rebound after 2 years off ART. In contrast, there was only one viral rebound in the vaccine group. Three out of four vaccinees had no viral rebound, even after CD8 depletion, and they remain in drug-free viral remission more than two years later. The strategy of early ART combined with immunotherapy can produce a sustained SIV remission in macaques and may be relevant for immunotherapy of HIV in humans.