Experimental HIV vaccine not effective in preventing HIV acquisition no safety concerns identified

Cape Town | A study analysing whether an experimental HIV vaccine regimen was safe and able to prevent HIV infection in a high-incidence population of young women in sub-Saharan Africa, will not progress further. This follows data that the experimental vaccine did not effectively prevent HIV acquisition – however, no significant safety concerns were identified throughout the trial.

While the rest of the world continue to grapple with the COVID-19 pandemic, the development of a safe and effective HIV vaccine also remains critical for global health. In the more than 40 years since the virus was discovered, a vaccine has proved elusive because of the virus’ unique ability to attack and evade the immune system.

Launched in November 2017, the Imbokodo Study, also known as the HVTN 705/HPX2008, reached full enrollment in 2019, and completed vaccinations in June 2020. The primary aim of the study was to evaluate the experimental regimen in approximately 2,600 women between ages 18 and 35 across five sub-Saharan Africa countries including: Malawi, Mozambique, South Africa, Zambia and Zimbabwe. According to UNAIDS, women and girls accounted for 63% of all new HIV infections in this region in 2020. The South African Medical Research Council (SAMRC) was instrumental in the implementation of the study.

The experimental vaccine consisted of an adenovirus containing four “mosaic” immunogens – called mosaic because they are designed to induce immune responses against multiple global HIV strains. The regimen included four doses of the mosaic Ad26 vaccine; the final two doses were given together with doses of an HIV protein called clade C gp140 mixed with an aluminum phosphate adjuvant to boost immune response. Different HIV subtypes, or clades, predominate in various geographic regions around the world. Clade C HIV is common in southern Africa, where the Imbokodo study was conducted.

In preclinical studies, regimens with mosaic-based vaccines elicited a strong immune response associated with protection against HIV in monkeys. Findings from two early-stage human clinical trials, called TRAVERSE and APPROACH, also suggested that these vaccines were well-tolerated and could generate anti-HIV responses in healthy adult volunteers, increasing hope for good results in the Imbokodo trial. The vaccine was initially developed by the laboratory of Dan H. Barouch, M.D., Ph.D., at Beth Israel Deaconness Medical Center and Co-Principal Investigator of the HVTN, together with Janssen and other partners.

Although the study failed to meet its primary endpoint, with results falling short of statistical significance, the data and safety monitoring board (DSMB) did not express any concern regarding participant safety throughout the trial. Participants in this Phase2b proof-of-concept study will be unblinded and will continue to be referred to high-quality treatment and care.

According to study investigators, while they are disappointed with this outcome, the results are an important scientific finding in the ongoing pursuit for an effective vaccine to prevent HIV. They also say that the study has also provided enough data to proceed with key immunological correlates research. “HIV is a unique and complex virus which has long posed unprecedented challenges for vaccine development. The lack of natural human recovery combined with the virus’ ability to attack, hijack and evade the immune system pose substantial challenges”.

“The high rates of HIV acquisition seen in the Imbokodo study of young women in sub-Saharan Africa remind us that, despite great progress made in treatment and prevention, HIV remains a huge health challenge for the region,” said Prof Glenda Gray, President and CEO of the SAMRC, who is also the Protocol Chair and Co-Principal Investigator and Director of HVTN Africa Programs. “This underpins the need to apply the knowledge gained from this trial to continue to advance the pursuit of a global HIV vaccine.”

Although the Imbokodo study will not continue, another HIV vaccine trial is ongoing in a different population and in different areas of the world. The Phase 3 Mosaico study, or HVTN 706/HPX3002, is testing the safety and efficacy of an “optimized” experimental vaccine regimen that includes the same mosaic Ad 26 priming immunogen but has an optimized booster regimen that includes a mosaic envelope plus a Clade C booster. This optimized booster gives higher and broader immune responses than the booster used in Imbokodo. Study participants are men who have sex with men (MSM) and transgender populations in North America, Latin America, and Europe.

Prof Gray, alongside her co-Principal Investigator, Prof Larry Corey from the HVTN Leadership Operations Center, which is based at the Fred Hutchinson Cancer Research Center, said the Imbokodo research team will continue to analyze data from the study and publish complete findings to guide future investigations and vaccine development.

Prof Corey highlighted that despite the use of the Ad 26 technology, which is effective for COVID-19, the Imbokodo study illustrates that HIV is an infection that requires a higher degree of immune response to achieve effective protection. “We hope the details from the trial will provide evidence for what level of immune responses are required to achieve an effective vaccine. The study team and entire HVTN operations program thanks everyone who participated in this study, which will continue to provide important data to help drive forward the search for an HIV vaccine.”

NOTE TO THE EDITOR:

More about the Study:

The Imbokodo study was supported by a public-private partnership led by Janssen Vaccines & Prevention B.V.; the Bill & Melinda Gates Foundation; the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH); and the HIV Vaccine Trials Network (HVTN), headquartered at the Fred Hutchinson Cancer Research Center in Seattle. Additional partners providing support included the U.S. Army Medical Research and Development Command (USAMRDC) and the Ragon Institute of MGH, MIT and Harvard. The study was conducted at clinical sites coordinated by HVTN, and the South African Medical Research Council (SAMRC) helped to implement Imbokodo in South Africa.

For more information about Imbokodo, also known as HVTN 705/HPX2008, please visit https://www.imbokodo.org.za or see ClinicalTrials.gov using identifier NCT03060629.