The results are “encouraging, but very preliminary.” First results from a French trial of a prophylactic HIV vaccine by Inserm and the National Agency for Research on AIDS and Viral Hepatitis (ANRS) show that their vaccine candidate called “CD40.HIVRI.Env” is safe and induces an early, strong and long-lasting immune response . Science et Avenir summarizes what this means and that this study offers hope in the fight against HIV, the virus responsible for AIDS.
How does this innovative technology vaccine work?
This vaccine candidate is based on the injection of HIV proteins associated with monoclonal antibodies. They target a receptor on the surface of dendritic cells, the CD40 molecule responsible for alerting the immune system. This is the first time that a vaccine has directly targeted these cells, which play a key role in learning and activating the immune system.
“The vaccine itself is innovative because it is based on the most current knowledge of the immune response that we have learned,” explains Yves Levy, an immunologist in the Department of Clinical Immunology and Infectious Diseases at the Henri-Mondor Hospital (AP-HP) and Director of Science Vaccine Research Institute. After the intramuscular injection, there was still a black box, reactions that we could not observe. It could only be observed later, in the blood, noting the cellular response or the presence of antibodies.”
This time, the team wanted to “look into the black box” to better understand the mechanisms at work. “We already knew that certain cells under the skin, dendritic cells, play a critical role in inducing an immune response. They are part of the immune system and are able to trap external agents penetrating the skin to present them to the immune system, which in turn creates a response.”
The ANRS team then developed a technology similar to biotherapy, created using genetics. “After studying 1,000 antibodies, we chose one that targets one of the receptors, CD40. We then fuse with this antibody fragments of HIV selected using a bioinformatics approach and corresponding to group C clades that are found in Africa.”
What results have been seen?
Trials began in May 2021 on healthy volunteers without chronic diseases or infections. Three cohorts of 12 patients each received doses 4 weeks later and then 6 months after the first injection. Result: “excellent” tolerability without grade 3 or 4 events that would require termination of the clinical study due to hazard. In addition, this study is double-blind and placebo administered to some volunteers.
The phase I trial ended in October 2022. A response was observed in all volunteers in 3 cohorts after 2 injections. “We are seeing antibody production at an early stage, a broad response that allows recognition of multiple clades of HIV. Moreover, this dose of antibodies was very high, much higher than the last positive results obtained in 2009 in Thailand as part of the HIV test.”
In addition, neutralizing antibodies capable of blocking the virus were observed in 50% of the volunteers at the first dose, then in 100% of the volunteers at the second dose. The researchers also observed the production of CD4 T cells specifically directed against the HIV envelope protein after vaccination, which remain stable over time.
What can we expect in the future?
The positive news comes in a pessimistic context following the announcement of negative results for Janssen’s Mosaico vaccine, which showed no effect in the 6,000 people included in the study. However, ANRS wants to be cautious: “The effectiveness of the vaccine has yet to be demonstrated” in Phase II/III clinical trials. Although there was a significant immune response during this first phase, this does not really allow us to conclude that if these volunteers had been exposed to HIV, their bodies would have been able to protect themselves from infection.
For now, the team will continue to monitor the volunteers for 12 months. In parallel, trials are ongoing with additional groups of volunteers who received “CD40.HIVRI.Env” linked to a DNA vaccine that could enhance the immune response. “The idea is to makethe same antigens in two different ways to test all strategies,” explains Yves Levy.
However, these first positive results allow us to look a little further and imagine a new study, this time more extensive. “We have reached criteria that allow us to consider moving to the next phase, and we are now discussing phase II trials with the same vaccine candidate,” explains Yves Levy. “We learned that changing antigens, adjuvants, or the route of administration did not always replicate the good results of the first phase.” So the idea is to start a new study with exactly the same vaccine.