Additional authors include: Richard Jefferys, Treatment Action Group, Ntando Yola, Desmond Tutu HIV Foundation
In the first of the three MBC sessions we heard from Dr. Susan Buchbinder, San Francisco Department of Public Health, who gave an overview of the MOSAICO trial and the reasons for its discontinuation. MOSAICO was stopped after the Data Safety Monitoring Board (DSMB) did their review and found that, whilst the product was safe, it did not meet their predefined criteria for efficacy.
The MOSAICO vaccine was intended to work against globally relevant strains and subtypes of HIV. It used an Ad26 vector (like that of a cold virus), a mosaic insert (including a variety of global HIV strains) and a Clade B and gp140 envelope to prevent HIV infection.
The type of vaccine used in the MOSAICO study provides binding and functional antibodies (not neutralising antibodies), which had proved to give some protection in studies with non-human primates.
Let’s refresh our memory on what the difference is between the types of antibodies:
- Neutralising antibodies work to neutralise and clear the virus,
- Non-neutralising antibodies like binding antibodies bind to the virus,
- Functional antibodies use cells, like T cells, to clear the virus.
The sister study to the MOSAICO trial, the Imbokodo trial, in women in Southern Africa used the same vaccine regimen, with some slight differences. In 2021, non-efficacy was found in this study. However, it was decided to continue the MOSAICO study because of the differences (as they used a Clade C and gp140, they took place in a different population, was protecting against different subtypes and PrEP use was different in the populations involved).
The MOSAICO study population was 18–60-year-old transgender men and men who have sex with men with sites mainly in Latin America. The study, started in November 2019, was recommended to stop on 12 January 2023. Participants were notified and informed of which arm they had been participating in. There were no safety issues with the vaccine.
The main takeaway, as further stated by Richard Jefferys, Community Activist from Treatment Action Group, is that the key question on which antibodies can protect against HIV has been answered. Indeed, the non-efficacy shown in this study suggests that, unlike vaccines that provide non-neutralising antibodies, vaccines that can induce broadly neutralising antibodies can protect against HIV infection.
Richard also drew the attention to the fact that essential lessons were learned in the study in terms of community engagement in HIV vaccine trials. The community were involved at all stages of the process: involvement in the protocol team; reviewing informed consent forms; members of community ethicists; community discussions on how to handle PrEP within the trial; community advisory boards at each site.
With these key lessons learned, there is plenty more discussion to be continued on the next steps of HIV vaccine research.
To watch the recording of the session head over to https://youtu.be/idsozzkEteY
Editor’s Note: This article was first published by the European AIDS Treatment Group, it has been republished with their permission. https://www.eatg.org/news/croi-2023-reporting-from-margarita-breakfast-club-session-1/