One HIV Vaccine Fails While a First-of-its-Kind mRNA Vaccine Trial is Set to Begin

As one company announced that its HIV vaccine candidate fell short of its goal in a mid-stage trial, another is set to begin recruiting for the first mRNA trial for 2 experimental vaccines for the virus, a historic mark in the fight against HIV.

Johnson & Johnson (J&J) this week announced that its experimental HIV vaccine that uses the same technology as its COVID-19 vaccine was not effective at preventing infection in women. The phase 2b Imbokodo study, which included more than 2,000 women in southern Africa, assessed whether the HIV vaccine could reduce the risk of infection by half, finding that the vaccine was able to lower infection rates by 25.2%.

The announcement is the latest blow to the development of a vaccine that can effectively prevent HIV infection, which has evaded researchers since the start of the HIV/AIDS pandemic four decades ago.

However, amid the failure of the Imbokodo trial also comes the anticipation of a new approach to HIV vaccines using mRNA technology, which researchers hope can turn the tide on the promise of a vaccine for these patients.

A trial will soon be under way for Moderna’s two vaccines, mRNA-1644 and mRNA-1644-v2-Core, which are built on the same mRNA platform used for the company’s COVID-19 vaccine. With mRNA vaccines, the injected RNA carries the code for the antigen, which is produced in abundance and provokes the immune system to produce antibodies. Once primed to recognize the antigen, the immune can more effectively fight off infection when it encounters the virus.

Moderna is aiming to enroll just over 50 patients between the ages of 18 and 50 years in this phase 1 trial. The study is estimated to be completed in the spring of 2023. Sponsors and collaborators of the study also include the International AIDS Vaccine Initiative, The University of Texas at San Antonio, Fred Hutchinson Cancer Research Center, George Washington University, and Emory University.

Moderna’s vaccine approach aims to overcome what has proven to be the biggest barrier to developing an effective HIV vaccine over the course of the pandemic: producing enough neutralizing antibodies — antibodies that defend cells from pathogens such as the HIV virus.

To date, all other HIV vaccine trials, including the Imbokodo trial, have assessed the potential of adenovirus vaccines — vaccines that inject an altered form of a virus to trigger an immune response and produce antibodies against the virus.

Although J&J announced that the Imbokodo study will not continue based on the recently announced results, its second trial called Mosaico will continue. This phase 3 trial is using a similar vaccine but among nearly 4,000 transgender people and men who have sex with men. Both trials use mosaic vaccines, which combines pieces of different strains of the HIV virus. The trial is expected to be completed in 2024.

The least four decades have seen multiple HIV vaccine trials fail to prevent infection across different populations, including the HVTN 702 trial, which was cut short in 2020 after data showed the vaccine was not effective across the 5400 participants. Notably, in 2007, Merck’s vaccine candidate was actually shown to increase the risk of participants being infected with HIV.

Glimmers of hope came about in 2009 based on data from the Thailand-based RV-144 trial (also known as the phase 3 Thai trial),which looked at how well the experimental vaccine could prevent HIV and reduce the amount of HIV viral load in patients who contracted the virus after enrolling in the trial. More than 10,000 people were enrolled in the study, and results were just shy of being statistically significant, protecting against HIV in 31% of patients over 3.5 years.

Subsequent analyses of the trial have shown that the protective efficacy was actually 60% in the first year, prompting future trials to try and build on the results and create more lasting responses.