Large-Scale HIV Vaccine Trial to Launch in Southern Africa
Scientists in Southern Africa are conducting clinical trials to test HIV vaccine regimens designed for the region where the HIV burden is greatest. Early-stage trials began in early 2015 to accelerate progress toward the potential licensure and delivery of a safe, effective HIV vaccine that could achieve a broad public health impact.
The research is driven by the Pox-Protein Public-Private Partnership (P5)—a diverse set of public and private organizations committed to building on the success of the RV144 HIV vaccine trial, which showed a modestly protective effect. The P5 aims to produce an HIV vaccine that could have a significant public health benefit in southern Africa and to deepen scientists’ understanding of the immune responses associated with preventing HIV infection. P5 members are NIAID, the Bill & Melinda Gates Foundation, the South African Medical Research Council, HVTN, Sanofi Pasteur, GSK and the U.S. Military HIV Research Program. P5 partners joined forces in 2010 to improve and prolong the level of protection seen in RV144.
In May 2016, P5 partners announced the decision to move forward with the Phase IIb/III HVTN 702 vaccine study, based on primary analyses from an ongoing Phase I/II clinical trial. When it launches in late 2016, HVTN 702 will be the most advanced efficacy trial of an HIV vaccine candidate currently in the field.
P5 studies across Southern Africa test a range of vaccine formulations, harnessing resources from multiple sectors to solve challenges in research, product development and manufacturing. P5 members work with governments and communities within host countries to develop collaborative clinical development plans and initiate regulatory and access planning.
The Road from RV144
2009: The RV144 vaccine trial, led by the U.S. Military HIV Research Program, with the Thai Ministry of Health, provided the first evidence in humans that a safe and effective preventive HIV vaccine is possible. Final efficacy was 31%, despite a higher early effect (60%) at 12 months.
2010-2012: The P5 was formed to build on RV144 results in Southern Africa. P5 partners developed and manufactured a vaccine adapted to subtype C, prevalent in Southern Africa. Trial design began, based on RV144. New correlates of risk information and “go”/“no-go” criteria were developed to guide development of large-scale studies.
2013-2014: An initial study (HVTN 097) to evaluate the RV144 vaccine regimen in South African volunteers showed that the regimen was safe and well-tolerated.
2015: A Phase I/II study of the modified RV144 regimen, HVTN 100, launched in Southern Africa.
2016: Primary analyses of HVTN 100 safety and immune response data informed the decision to launch the Phase IIb/III HVTN 702 study.
Studies to Evaluate Vaccine Efficacy and New Regimens
The P5 is working to extend the benefit of a formulation with proven potential and explore new HIV vaccine formulations.
This work includes supporting the potential licensure of a subtype C-based HIV vaccine similar to the pox-protein, prime-boost regimen pioneered in RV144. To improve efficacy, the trials are testing a new adjuvant that could enhance the immune response. Researchers will also test a vaccination boost to prolong protection.
HVTN 100, launched in 2015 to test the vaccine regimen’s safety and efficacy. The trial uses a modified version of ALVAC, the pox vector vaccine from RV144, followed by boost vaccinations with a protein product.
HVTN 100 will conclude in late 2016, but primary analysis showed that it clearly met all pre-specified criteria to proceed with a large-scale Phase IIb/III trial. That efficacy study, HVTN 702, will launch in late 2016 to evaluate whether this vaccine can help prevent HIV infections in 5,400 volunteers.
Research in Thailand Continues to Build on RV144 Insights
Following the RV144 results, the U.S. Military HIV Research Program (MHRP) initiated follow-up studies in Thailand to evaluate the immune mechanisms generated by the original vaccine regimen and the effects of an additional boost.
One study, RV305, evaluates re-boosting the volunteers who participated in RV144. Through this study, MHRP researchers have determined that the most effective boost is when both ALVAC (Sanofi Pasteur) and AIDSVAX (GSID) are given together, or when AIDSVAX is given alone. Researchers have also found that late boosts given six to eight years after initial vaccination produce promising immune responses.
Another study, RV306, uses the RV144 vaccine regimen to compare additional vaccine boosts and gather immunogenicity data in 360 new volunteers to explore how boost timing may impact immune responses.
HIV Prevention Research: A Global Effort
The P5’s vaccine research is an important part of the comprehensive approach to HIV prevention and joins a robust and diverse HIV vaccine research pipeline that includes more than 30 early-stage clinical trials.
P5 trials in Southern Africa engage scientific, political and community leadership to expand HIV research capacity in the region as part of the urgent search for new, cost-effective prevention tools. The research will provide insights into the immune responses that protect against HIV and could inform the development of other prevention tools and strategies.
More than two million people become newly infected with HIV every year – the vast majority in Southern Africa – because they lack prevention methods that meet their needs. Continued investment in the complete HIV vaccine pipeline is critical to reducing new HIV infections and bringing about a durable end to the HIV/AIDS epidemic.
P5: A Public-Private Partnership to Accelerate HIV Vaccine Product Development
The P5 has assembled a collaborative team across four continents to accelerate progress toward a safe and effective HIV vaccine. Public-private coordination ensures the P5 can act quickly on positive results to expedite potential HIV vaccine licensure and make a successful vaccine available to those at highest risk.
Vaccine trials in Southern Africa are being conducted by the HIV Vaccine Trials Network (HVTN) with funding from the National Institutes of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the Bill & Melinda Gates Foundation. Additional funding is provided by the South African Medical Research Council (MRC). Subtype C-based vaccine products are manufactured by Sanofi-Pasteur and GlaxoSmithKline. The U.S. Military HIV Research Program (MHRP) leads clinical trials in Thailand in collaboration with the Thai Ministry of Health.
Pox-Protein Public-Private Partnership (P5) Members and Collaborators
- U.S. National Institute of Allergy and Infectious Diseases/Division of AIDS (NIAID)
- Bill & Melinda Gates Foundation
- HIV Vaccine Trials Network (HVTN)
- South African Medical Research Council (MRC)
- Sanofi Pasteur, the vaccines division of Sanofi
- U.S. Military HIV Research Program (MHRP)
- GlaxoSmithKline (GSK)