Building on the Success of RV144
In 2009, the RV144 Thai vaccine trial provided the first evidence in humans that a safe and effective preventive HIV vaccine is possible. Although efficacy was 31.2% at the end of the study, it appears there was a higher early effect (60%) at 12 months.
The Pox-Protein Public-Private Partnership (P5) is a diverse group of organizations committed to building on the success of the RV144 HIV vaccine trial and evaluating potentially improved pox-protein vaccines to determine if they might provide significant public health benefit. Follow-up clinical studies using improved vaccine regimens in southern Africa and Thailand are being planned.
Planned Clinical Studies
The P5 has been planning future efficacy studies, and members are working with government and communities within potential host countries to develop collaborative clinical development plans, as well as initiating regulatory planning and access agreements.
The planned studies are sequential, and therefore the plans for large-scale clinical trials may change as researchers gather information from smaller studies about product safety and immune responses. In addition, trial start dates are dependent on many factors and are likely to change.
A unique aspect of the large-scale studies is that new go, no-go criteria have been developed to help determine if those studies should move ahead. These decisions will be based on many factors such as vaccine potency and the ability to further test the hypotheses generated by the RV144 trials.
The clinical trial implementation in southern Africa will be led by the HIV Vaccine Trials Network (HVTN) and studies in Thailand will be led by the U.S. Military HIV Research Program (MHRP), in collaboration with the host country governments and ministries.
Improving the Vaccine Regimen
Researchers have discovered important clues about the immune responses that may have played a role in protecting some volunteers in RV144. The data from extensive laboratory studies on correlates of risk of HIV infection will be used in one aspect of clinical trial design planning.
In parallel, scientists with the P5 have been developing, analyzing and selecting protein components of the vaccine candidates to use in planned studies. They hope to improve and prolong the level of protection seen in RV144 by using an extra vaccine boost and different adjuvants that may increase and prolong antibody responses.
The U.S. Military HIV Research Program (MHRP), which led the RV144 trial with the Thai Ministry of Public Health, initiated several follow-on clinical studies to conduct intensive immunogenicity research. The data from these studies are informing future clinical research by providing insights into the immune mechanisms generated by the RV144 regimen and the effects of an additional boost. Details on these studies are below:
- Evaluating re-boosting at Month 0, 6 with AIDSVAX, ALVAC, or combination volunteers who participated in the RV144 study
- Intensive systemic and mucosal immunogenicity
- Started May 2012; n=162
- All vaccinations completed; initial immunogenicity results in late 2013
- RV144 vaccine regimen + month 12 boost with ALVAC, AIDSVAX, or combination
- Gather intensive systemic and mucosal immunogenicity data
- Started September, 2013; n=360
- AIDSVAX alone for intense immunologic assessments
- Start in early 2014; n=40
Southern Africa Clinical Trials
The HIV Vaccine Trials Network (HVTN) plans to conduct clinical trials in heterosexual adults that will evaluate a prime-boost vaccine regimen similar to that used in RV144 adjusted to target the most common subtype of HIV in the region (subtype C).
A modified version (subtype C) of ALVAC, the pox vector vaccine used in RV144, will be used as the prime or first vaccination received by study participants. That prime will be followed by the boost vaccinations with the vector and Bivalent gp120, a protein product adjusted for subtype C.
The name “Uhambo” was chosen to encompass all the studies that HVTN will perform in southern Africa. Uhambo, a word meaning “opportunity” in Shona and “journey” in Xhosa, was chosen to represent both the great opportunity to stop the spread of HIV and the journey towards finding a safe and effective preventive HIV vaccine. The development track will include a Phase I trial to test the vaccine regimen’s safety and immunogenicity, and a larger efficacy study, HVTN 702, will follow. Trial start dates are dependent on many factors including the selection and preparation of more than two-dozen clinical trial sites as well as the manufacturing and availability of vaccine products.
The HVTN also plans to test other HIV vaccine regimens in southern Africa in a parallel research track using multiple vaccine candidates. These studies may provide additional clues on important immune responses to prevent HIV infection if the regimens prove effective. The study design allows for flexibility to accelerate progress and potentially identify new correlates.
This study, called HVTN 701, is a unique, two-part trial design with Part A being a Phase I trial for safety and immunogenicity, and Part B being a Phase IIb to test safety, immune responses and efficacy. Study products will include NYVAC, another pox vector vaccine, a DNA vaccine and protein mixed with one of two different adjuvants.
Thailand Clinical Trials
MHRP, in collaboration with the P5, is planning an efficacy trial in a high-risk population of men who have sex with men (MSM) to hopefully improve upon the RV144 result and extend its relevance to at-risk populations to achieve the greatest public health impact.
In 2012, a private-public partnership called the AIDS Vaccine Efficacy Consortium (AVEC) was formed to accelerate the development and testing of a pox-protein HIV vaccine prime-boost regimen in Thailand.
In August, 2013, the Kingdom of Thailand announced its commitment to support a future efficacy study at the AVEC Summit for an AIDS-Free Generation in Thailand. The Thai Government will take a leadership role by supporting a future HIV vaccine efficacy study and assist in establishing a flexible biologics manufacturing capability that could support HIV vaccine production in Thailand.
Current Pox-Protein Public-Private Partnership (P5) Members
- Bill & Melinda Gates Foundation
- HIV Vaccine Trials Network
- Novartis Vaccines and Diagnostics
- Sanofi Pasteur
- South African Medical Research Council
- U.S. Military HIV Research Program
- U.S. National Institute of Allergy and Infectious Diseases/Division of AIDS
For more information: P5info@mail.nih.gov
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