Efficacy trial under way for Janssen’s HIV vaccine

Anthony Fauci

The NIH and partners recently announced the launch of a large phase 2b trial evaluating the efficacy of Janssen Pharmaceutical’s investigational HIV vaccine.

The vaccine is designed to protect against a wide variety of HIV strains. It is based on “mosaic” immunogens that are created with genes from different subtypes of HIV-1, according to the NIH. The immunogens are delivered through an engineered version of a common cold virus known as adenovirus serotype 26 (Ad26).

“The ultimate goal is to deliver a ‘global vaccine’ that could be deployed in any geographic region to help protect vulnerable populations at risk of infection,” Johan Van Hoof, MD, therapeutic area head for infectious diseases and vaccines at Janssen, said in a press release.

Several different formulations of mosaic-based HIV vaccines have been evaluated in two phase 1/2a clinical trials, APPROACH and TRAVERSE. After reviewing results from the APPROACH trial and preliminary data from the ongoing TRAVERSE trial, researchers selected a lead vaccine regimen containing four mosaic antigens (Ad26.Mos4.HIV) and a soluble protein (Clade C gp140), adjuvanted with aluminum phosphate.

The proof-of-concept phase 2b study, known as “Imbokodo,” will compare the efficacy of the vaccine with placebo in 2,600 sexually active women from sub-Saharan Africa. “Imbokodo” is the Zulu word for “rock” and is part of proverb in South Africa that signifies the strength of women and their important role in the community, according to the NIH. UNAIDS estimates that women and girls account for nearly 60% of HIV infections in eastern and southern Africa, where 43% of new HIV infections occur each year.

Participants have already started to receive vaccinations at sites in South Africa, the NIH reported. Researchers are seeking regulatory approval to study the vaccine at additional sites in Malawi, Mozambique, Zambia and Zimbabwe. The participants will receive vaccinations at four time points over the course of 1 year and will be followed for at least 2 years.

This is the second HIV vaccine that is currently being evaluated in an efficacy trial. The National Institute of Allergy and Infectious Diseases launched a phase 2b/3 trial, HVTN 702, late last year to assess a newer version of a vaccine that was tested during the RV144 Thai trial. Results from RV144, released in 2009, showed that the vaccine was 31.2% effective at preventing HIV over a follow-up period of 3.5 years. HVTN 702 was the first new efficacy trial for an HIV vaccine in 7 years, according to a press release.

“It is important to have simultaneous vaccine efficacy trials,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told Infectious Disease News. “Our experience over many years of research has taught us that there needs to be more than one iron in the fire because if one vaccine fails, you do not want to have to wait years for the next one.”

What remains the greatest challenge in HIV vaccine development is determining how to get the body to produce an immune response that can control and ultimately clear the virus, Fauci said.

“Part of vaccine development is being able to mimic natural infection. The body can naturally produce immune responses against other viruses like smallpox and measles. This immune response leaves people with long-term protection against the same virus,” he explained. “We have not seen that with HIV. So, we have to create a vaccine that can produce an immune response that not even natural infection induces.”

The NIH expects results from HVTN 702 in 2020 and results from Imbokodo in 2021.

“To have an effective vaccine in addition to the existing prevention modalities, such as treatment as prevention and pre-exposure prophylaxis, will give us another important tool in the HIV armamentarium to control and essentially end the epidemic,” Fauci said.

Disclosures: Fauci reports no relevant financial disclosures. Van Hoof is an employee of Janssen Pharmaceuticals.