Combined approach of vaccine and antiviral drugs can achieve better protection in NHP model against heterologous SHIV challenges
Background: Vaccine is needed to stop the AIDS pandemic. Even low efficacy vaccine can prevent millions HIV infections according to mathematic models. Unlike the rapid advances in antiretrovirals since 1990s and in biomedical interventions of recent years, HIV vaccine research has been struggling due to the unprecedented challenges it met. The best results of oral Prep of antiretrovirals and RV144 vaccine showed around 50% and 30% protective efficacy respectively in clinical trials. The strategy of combining various prevention approaches, such as vaccines and antiretrovirals, should be tested to achieve higher prevention.
Method: Rhesus macaques were immunized with DNA, recombinant vaccinia virus (replicating recombinant Tiantan expressing HIV-1 gag/pol/env and SIV gag.) and protein The immunized animals were given oral TDF/FTC before challenged by multiple low dose SHIV SF162 P3 through rectal mucosal. Immune responses and viral load were monitored for evaluation.
Result: Among the 4 groups of monkeys (8 per group), high peak viral loads (3.8 x 106) can be detected in all animal of the control group and reduced peak viral load were detected in 4 (1.7x 105), 3 (2.9x 103) and 1 (1x 103) animals of the vaccine only, antiviral drug only and vaccine/ antiviral drug combined groups respectively. The reduced viral load in the three treated groups also resulted in low viral set-point and faster felling to undetectable levels, compared to the control group. Both strong humoral (binding and V1V2 antibodies) and cellular (CD8 and CD4) responses to HIV-1 antigens and SIV gag can be detected in immunized animals.
Conclusion: High protective efficacy (87.5%) can be achieved by the combined use of vaccines and antiretrovirals. Experiments are pending to evaluate the mechanism of protection in protected animals, as well to the impact of the treatment on the viral reservoirs in the infected animals.