The rapid production and incredible efficacy of the COVID-19 vaccine may have offered a skewed perception of vaccine production challenges. But researchers who develop HIV vaccines know those challenges all too well. This week, the National Institute of Allergy and Infectious Diseases (NIAID) released a disappointing update from a Phase IIb proof-of-concept study, which began in November 2017, for an investigational HIV vaccine made by Johnson & Johnson. The data from the “Imbokodo” clinical trial conducted in sub-Saharan Africa—which enrolled 2,637 women ages 18 to 35 years from five countries—suggest that the HIV vaccine posed no safety concerns but did not provide sufficient protection against HIV infection.

The Imbokodo primary analysis was conducted 24 months after participants received their first vaccinations. The study’s primary endpoint was based on the difference in the number of new HIV infections between the placebo and vaccine groups from month seven (one month after the third vaccination timepoint) through month 24.

When comparing the number of new HIV infections between study participants who were randomly assigned to receive either placebo or the investigational vaccine, statisticians found that 63 participants who received the placebo and 51 participants who received the experimental vaccine acquired HIV infection. Therefore, the investigational vaccine’s efficacy was 25.2% (95% confidence interval of vaccine efficacy—10.5% to 49.3%).

“The development of a safe and effective vaccine to prevent HIV infection has proven to be a formidable scientific challenge,” said Anthony S. Fauci, MD, director of the NIAID. “Although this is certainly not the study outcome for which we had hoped, we must apply the knowledge learned from the Imbokodo trial and continue our efforts to find a vaccine that will be protective against HIV.”

The study vaccine was found to be safe with no serious adverse events associated with it. Study participants are being informed of the findings and will have follow-up visits with the study investigators. Further analysis of the Imbokodo study will continue, and the study is thought to have provided sufficient data for further immunological correlates research.

The investigational vaccine tested in the Imbokodo study is based on “mosaic” immunogens—vaccine components designed to induce immune responses against a wide variety of global HIV strains. The vaccine candidate used a strain of common-cold virus (adenovirus serotype 26, or Ad26) to deliver four (quadrivalent) mosaic antigens to spur an immune response. Earlier research indicated the vaccine was both well-tolerated and could induce an anti-HIV immune response. Imbokodo participants received four vaccinations during a one-year period. This included four doses of the investigational quadrivalent vaccine. The final two doses were administered together with doses of an HIV protein, clade C gp140, and an adjuvant to boost immune responses. Participants were followed for at least two years. The primary analysis occurred one year after the last study participant’s final vaccination.

Study participants were offered pre-exposure prophylaxis medication to prevent HIV infection during the clinical trial. The women who acquired HIV infection were directed to medical care and offered antiretroviral treatment.

The Imbokodo study, also known as HVTN 705/HPX2008, is sponsored by Janssen Vaccines & Prevention, part of the Janssen Pharmaceutical Companies of Johnson & Johnson. It is funded by two primary partners, the Bill & Melinda Gates Foundation (BMGF) and the NIAID.