A safe, effective HIV vaccine is key to ending an epidemic that continues to kill nearly one million people a year. MHRP is engaged in advancing next-generation vaccine concepts and evaluating novel strategies involving rapid dose administration, late boosting and fractional dosing.
The Army-led RV144 “Thai Study” was the first clinical trial to show modest efficacy in preventing HIV infection, and the landmark trial continues to provide scientific direction to help guide vaccine development and testing. MHRP scientists conducted RV144 follow-up studies to discover correlates of risk, provide targets for optimizing vaccine boosting and critically compare the regimen against more recent HIV vaccine candidates.
The RV305 study examined the effect of late boosting to the original RV144 regimen. Healthy participants from the original RV144 trial received a late vaccination 6-8 years post RV144, and a sub-study evaluated an additional boost given 9-12 years post RV144. Results, published in the Journal of Infectious Diseases, showed boosted participants had immune responses stronger in magnitude than peak immune response in RV144, indicating the original RV144 series laid down longterm immune memory. This research supports the concept of the prime-boost regimen as a strategy.
MHRP researchers conceived of RV306 to assess the effect of an additional vaccine boost to the RV144 regimen at varying intervals between the priming vaccine series and the boost. Naïve, healthy volunteers received the RV144 regimen, followed by an additional boost at month 12, 15 or 18. This trial also included extensive assessment of peripheral as well as mucosal responses upon vaccination. Results showed that longer intervals between the primary vaccination series and late boost improved immune responses and might improve the efficacy of preventing HIV acquisition, a strategy now being considered in the design of MHRP’s future vaccine trials. Findings were published in Lancet HIV.
Mosaic Vaccine Trials
MHRP is participating in trials of two investigational vaccines based on “mosaic” immunogens — vaccine components comprising elements from multiple HIV subtypes — that aim to induce immune responses against the wide variety of global HIV strains. Trials for these Ad26/mosaic candidates are called Imbokodo (HVTN 705) and Mosaico (HVTN 706).
Partner sites in Thailand and Uganda participated in a Phase 1/2a trial called APPROACH evaluating the Ad26/mosaic vaccine. APPROACH showed promising immune responses and helped lead to the Imbokodo efficacy study HVTN launched in 2017. MHRP helped conduct the initial preclinical studies that enabled the pathway to the Phase 2b vaccine efficacy study, and Program researchers continue as collaborators on the Imbokodo team.
The U.S. Army Medical Research and Development Command (USAMRDC), with technical support from MHRP, is part of a global partnership that launched Mosaico, the first large-scale Phase 3 efficacy study of an investigational mosaic-based HIV-1 preventive vaccine. The Phase 3 trial is enrolling 3,800 individuals in eight countries across North America, South America and Europe.
The study vaccines for both HVTN 705 and HVTN 706 are produced by Janssen Vaccines & Prevention B.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Other planned MHRP trials will seek to develop improved vaccine components and optimize regimens. The Army-developed Army Liposome Formula (ALF) will enter its first human trial in the coming year (RV460), a comparative adjuvant study taking place in Kenya that will also provide insight into the role of adjuvants in priming versus boosting. ALFQ will also be evaluated in Thailand (RV546) as part of a late boost regimen administered to healthy participants from the RV306 trial.
Another study in collaboration with Duke University will examine fractional dosing of a candidate HIV vaccine to determine whether smaller doses of valuable antigen will induce effective immune response, a variable that will help a potential vaccine reach more people.
MHRP researchers are also working on a dose escalation strategy they call RapidVax. The approach seeks to evaluate whether exposure to HIV antigen in escalating doses administered over several days, a pattern that mimics natural acute HIV infection, increases antibody magnitude and function.