Researchers reveal new findings that could cure HIV

After decades of research on how to combat the human immunodeficiency virus (HIV), its eradication begins to look possible. A vaccine therapeutic of T cells created in Spain, has demonstrated its ability to keep the virus under control in the absence of treatment antiretroviral. Once the proof of concept has been passed, the strategy needs to be perfected and, probably, new elements introduced to improve the results obtained.

The journal Nature Medicine published on October 27 the results of the Aelix-002 clinical trial, phase I/IIa, randomized and placebo-controlled, which support the ability of the HTI immunogen to enhance the body’s immune response of HIV-positive people to the point of suppressing the virus for a time in the absence of antiretroviral drugs.

This immunotherapy, from the Barcelona-based biotech Aelix Therapeutics, combines specific antigenic regions of HIV, where its development has been possible thanks to the study of individuals who can control the virus without the need for antiretrovirals (with a non-progressive clinical phenotype) and who usually generate a powerful immune response T cells against these regions.

Essay ‘Aelix-002’

The Aelix-002 study, which has had the collaboration of Gilead and has been carried out at IrsiCaixa, included 45 individuals who received antiretrovirals, had been treated early after infection and had been virologically suppressed for at least one year. The participants did not have any genetic factors that predisposed them to spontaneously control HIV.

Of these, 26 received the HTI immunogenby means of a complex vaccination regimen in which a DNA vector and two viral types were used: the modified Vaccinia Ankara virus (MVA) and the chimpanzee adenovirus ChAdOx1 used in the vaccine of AstraZeneca against covid-19.

The trial met its primary and secondary objectives of safety, tolerability, and immunogenicity. But the efficacy was also evaluated, and it showed that 40% of the vaccinated people (8 participants) managed to stay without treatment antiretroviral for at least six months versus 8% (only one patient) in the placebo group.

A relevant result is that the people who presented a response of T cells induced by the vaccine more powerful, were those that managed to better control the virus in the long term. “Aelix-002 has given us the best signs of efficacy of all clinical trials with therapeutic vaccines against HIV,” Christian Brander, scientific director of Aelix and head of the IrsiCaixa Host Cellular and Genetic Immunity Group, explains to this outlet. “It’s a proof of concept that the vaccine that we have used can induce an immune response of the T cells robust, and that this immune response has an effect on virus control.”

Main piece of the combined approach

From this study Brander understands that they already have the main piece to develop a combined approach that leads to healing. For now, she cautions that the virus control shown in the trial is “relative.” To improve the results “combinations of different interventions, immunological and virological, will be necessary, but what we will surely need will be a vaccine of T cells“, he maintains.

It highlights that the strategy must be optimized to improve the depth of the response (greater virological suppression), the duration of the effect and its scope to increase the percentage of responding patients. “We have not found the solution, but we are starting a path from a vaccine of T cells“he insists.

The great challenge for the cure and eradication of HIV is the complexity of the reservoir of viral latency: “With this trial we have begun to convince that it is an important field, but we still need to make the reservoir visible to these cells and induce strong responses. The key is in the regimen, the vectors and the adjuvants, and probably the combination with other components.”

Brander indicates that there is already encouraging preclinical data from a vaccine therapeutic with the HTI immunogen based on messenger RNA. On the other hand, among the other possible elements that accompany the immunotherapy of T cells Immunomodulators, other cellular vaccines, neutralizing antibodies, and immune checkpoint inhibitors are considered.

Combinations under study

In this sense, it is expected that the results of the phase II clinical trial Aelix-003 will be published imminently, which investigates whether Gilead’s oral immunomodulator vesatolimod, a toll-like receptor 7 (TLR 7) agonist, is capable of improving the response immunity induced by vaccines with the HTI immunogen based on viral vectors (MVA.HTI and ChAdOx1.HTI).

There are data in monkeys infected with the simian immunodeficiency virus (SIV) that demonstrate greater effectiveness in viral suppression with the combination of this drug. “We hope that vesatolimod can increase the response of T cells induced with the vaccinesince the magnitude of the response is directly related to the length of time without having to take medication.”

Likewise, he adds, in the phase I trial BCN03 of IrsiCaixa they are investigating a combined regimen of vaccines with the immunogen of T cells and another of B cells.

Finally, he announces that Aelix is ​​planning to carry out a new clinical trial that would also combine two types of immunotherapy: vaccination of T cells with a neutralizing antibody.

Immunogen design: less is more

Brander’s team at IrsiCaixa designed the HTI immunogen based on immunological information from nearly 1,000 individuals from four different HIV cohorts from three continents. “We had enough data from people who control HIV well, if not extremely well, and we wanted to see if responses against the virus based on T cells are different between controllers and non-controllers.”

In this way, they identified that these individuals with a non-progressive clinical phenotype generate responses of T cells against sixteen segments of HIV. “Most are not targets for the response of T cells in non-controllers, so we figured that if we could elicit responses in non-controllers against those segments we could turn them into controllers.”

“The logic in designing the immunogen is that less is more in this case, because the HIV virus causes such a strong response in the immune system that it suppresses it, and most patients die if left untreated. Therefore, we do not want to induce the responses of non-controllers, but rather restrict them to the most relevant and beneficial ones”, clarifies the researcher.

Consultation source here