He prefers to be cautious. Above all, would not want to “oversell” its results. Moreover, “they are not yet published, and the analyzes are in progress”. But nonetheless: Professor Yves Lévy is very keen to lift the veil on his data, and to let it be known that “his” anti-HIV vaccine has just taken an important step. Best known to the general public as the ex-boss of Inserm and husband of the former Minister of Health Agnès Buzyn, the immunologist has been working for more than ten years on the development of a preventive product against infection by the AIDS virus, with scientists from the Vaccine Research Institute (VRI) in Créteil. This vaccine is based on a breakthrough technology, never tested in humans until the launch last year of a first phase 1 trial. This protocol, known as “first-in-human”, therefore proved crucial.
“In animals, everything worked well, but we had no guarantee of obtaining a biological response in humans,” recalls Professor Lévy. Seventy-two healthy volunteers have agreed to be injected with the vaccine in recent months, “and it looks like the results are promising,” he says. No adverse events interrupted the program, and biological effects were measured, with both antibody and cellular responses. “It is still very preliminary: we will have more data by the end of the year. We will have to analyze it in terms of quality, quantity and duration. But we hope to be able to present it at the next World AIDS Congress in February 2023″, continues the researcher.
So far, all HIV vaccine projects have failed, at different stages of their development. Fifteen years ago, a product had shown protection rates of 30% in a phase 3 (large-scale) trial, but this result was never confirmed in other protocols. In question, the complexity of the virus: “It integrates into our genome, from where it can no longer be dislodged. It also presents a phenomenal variability, with hundreds of mutations, which make it different from one individual to the next. Finally, it is not “only” to protect against serious forms, but to block transmission, by inducing an antibody response in the mucous membranes”, explains Professor Gilles Pialoux, AIDS specialist (and columnist at the Express).
A “vaccine Everest”, therefore, which does not scare Yves Lévy: “We are bringing an original platform. By doing otherwise, with a new mechanism of action, it is possible that we will obtain different results”. The particularity of his vaccine? Targeting dendritic cells (which play a central role in activating the immune system) “more precisely than any other strategy”. The product will also be tested in combination with others, in first or second injection. All specialists believe that this so-called “prime-boost” strategy (the administration of two different vaccines) remains the best way to defeat HIV.
“The Covid has pushed manufacturers to take an interest in HIV again”
After having benefited from the public funding scheme Labex (laboratory of excellence) for ten years, Professor Lévy has also recently taken a step of another kind: the transfer of his technology to a start-up. An essential development to raise the funds needed for larger-scale trials and the industrialization of the product. For this, a “mutual friend” put him in touch with André-Jacques Auberton-Hervé, who had co-founded Soitec, which has become a heavyweight in global microelectronics. The meeting took place by Zoom, in full confinement. Between the renowned scientist and the endorsement physicist-businessman, who has since “followed a mook of immunology”, the contact has passed. Complementary, they co-founded LinKinVax, which now has around fifteen employees.
However, the road to a vaccine still looks long and uncertain. Especially since the competition is there: “Several trials are still in progress, and the success of research against Covid has prompted manufacturers to take an interest in HIV again”, notes Professor Pialoux. Starting with Moderna, the champion of anti-Covid vaccines, which has developed two different anti-HIV products, currently in phase 1 testing…
But like messenger RNA, the technology imagined by Yves Lévy can be applied to different microbes. The founders of LinKinVax are therefore also betting on other projects: a vaccine against cancers caused by the papillomavirus, another against chlamydia infections (responsible for sterility in women), and above all, against Covid. “Messenger RNA vaccines can be developed very quickly, but we hope that ours will induce a more durable and broader response”, indicates Yves Lévy. He therefore embarked on the race for the Holy Grail: a “pan-sarbecovirus” vaccine, which would protect against SARS-CoV-2 and its variants, but also against all the viruses of the same family. Two formulations are in development, with the Spike protein, like the other vaccines currently on the market, but also fragments of another protein (N), much less subject to mutations. A study of monkeys previously infected and then vaccinated (with one dose) showed that they were protected from reinfection and cleared the virus in an average of two days, compared to six for unvaccinated animals. Encouraging results, to be confirmed in humans. The first trials will start in 2023, in France in particular.