An early-stage clinical trial of a human immunodeficiency virus (HIV) vaccine, conducted in South Africa, has determined that an investigational vaccine regimen is safe and generates immune responses comparable with those reported in a landmark 2009 study showing that a vaccine can protect people from HIV infection.
Consequently, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), has decided to advance the experimental HIV vaccine regimen into a large clinical trial. This new study, called HVTN 702, is designed to determine whether the regimen is safe, tolerable, and effective at preventing HIV infection among South African adults. The study is scheduled to begin in November 2016, pending regulatory approval.
The experimental vaccine regimen that will be studied in HVTN 702 is now being tested in a smaller initial trial (HVTN 100) and is based on a regimen investigated in a clinical study in Thailand (RV144) led by the U.S. Military HIV Research Program, which delivered landmark results in 2009. The current regimen is designed to provide greater protection than the RV144 regimen, and it has been adapted to the HIV subtype that predominates in southern Africa.
The experimental vaccine regimen tested in the RV144 trial was found to be 31% effective at preventing HIV infection during the 3.5 years after vaccination, although the regimen appeared to have been 60% effective one year after vaccination. In the HVTN 702 study, the design and schedule of the RV144 vaccine regimen have been adjusted to try to increase the magnitude and duration of vaccine-elicited immune responses.
The NIAID is responsible for all operational aspects of the pivotal phase 2b/3 trial, which will enroll 5,400 HIV-uninfected men and women 18 to 35 years of age who are at risk for HIV infection. The NIAID-funded HIV Vaccine Trials Network (HVTN) will conduct the study. Results are expected in late 2020.
The HVTN 702 vaccine regimen consists of two experimental vaccines: a canarypox-based vaccine (ALVAC-HIV) and a bivalent gp120 protein subunit vaccine with an adjuvant that enhances the body’s immune response to the vaccine. Both ALVAC-HIV (supplied by Sanofi Pasteur) and the protein vaccine (supplied by GlaxoSmithKline) have been modified from the RV144 trial to be specific to HIV subtype C––the predominant HIV subtype in southern Africa. In addition, the protein subunit vaccine in the HVTN 702 trial is combined with MF59 (supplied by GlaxoSmithKline), a different adjuvant than the one used in the RV144 trial, in the hope of generating a stronger immune response. Finally, the HVTN 702 vaccine regimen will include booster shots at the one-year mark in an effort to prolong the early protective effect observed in the RV144 trial.
All study participants will receive a total of five injections during one year. The volunteers will be randomly assigned to receive either the investigational vaccine regimen or placebo.
Source: NIH; May 18, 2016.