The puzzle that will cure HIV begins to be completed

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After decades of research on how to combat the human immunodeficiency virus (HIV), its eradication begins to look possible.

A

has demonstrated its ability to keep the virus under control

.

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

published on October 27 the results of the

, phase I/IIa, randomized and placebo-controlled, which support the ability of the

to improve the immune response of the organism of seropositive people up to the point of suppressing the virus for a time in the absence of antiretroviral drugs.

This immunotherapy, from Barcelona-based biotech Aelix Therapeutics,

specific antigenic regions of HIV.

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 potent T-cell immune response against these regions.

Essay 'Aelix-002'

The

study , which has had the collaboration of Gilead and has been carried out at IrsiCaixa, included

, 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 immunogen through a complex vaccine regimen using a DNA vector and two viral types: the modified Vaccinia Ankara virus (MVA) and the chimpanzee adenovirus ChAdOx1 used in the AstraZeneca vaccine. against Covid-19.

The trial met its primary and secondary objectives of safety, tolerability, and immunogenicity.

But it also evaluated the efficacy, and showed that 40% of the vaccinated people (8 participants) managed to stay

for at least six months compared to 8% (only one patient) in the placebo group.

One relevant result is that people who had a stronger vaccine-induced T-cell response were those who managed to better control the virus in the long term.

"

has given us the

of all the clinical trials with therapeutic vaccines against HIV",

, scientific director of Aelix and head of the IrsiCaixa Host Cellular and Genetic Immunity Group, explains to this medium.

"It is proof of concept that the vaccine we have used can induce a robust T-cell immune response, and that this immune response has an effect on virus control."

Main piece of the puzzle

From this study Brander understands that they already have the main piece to develop a combined approach leading 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 T-cell vaccine," she says.

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.

"

, but we are starting a path based on a T-cell vaccine," she 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

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 notes that there are already encouraging preclinical data for a messenger RNA-based therapeutic vaccine with the HTI immunogen.

On the other hand, among the other possible elements that accompany T-cell immunotherapy are

, other cellular vaccines, neutralizing antibodies, and immune checkpoint inhibitors.

Combinations under study

In this regard, the results of the phase II clinical trial

are expected to be published imminently , which investigates whether Gilead's oral immunomodulator

, a toll-like receptor 7 (TLR 7) agonist, is capable of improving the response induced by the HTI immunogen vaccines based on viral vectors (MVA.HTI and ChAdOx1.HTI).

There are

infected with the simian immunodeficiency virus (SIV) that demonstrate greater effectiveness in viral suppression with the combination with this drug.

"We hope that vesatolimod may augment the vaccine-induced T-cell response, as 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

of IrsiCaixa they are investigating a combined regimen of vaccines with the T-cell immunogen and another for B-cells.

Finally, he announces that Aelix is ​​considering carrying out a new clinical trial that would also combine two types of immunotherapy: vaccination of T cells with a

.

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

, and we wanted to see if T-cell-based responses against the virus are different between controllers and non-controllers."

In this way they identified that these individuals with a non-progressive clinical phenotype generate T cell responses

.

"Most of them are not targets of the T-cell response in noncontrollers, so we figured if we could elicit responses in noncontrollers 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

ones", the researcher clarifies.

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• Infectious diseases

• AIDS and hepatitis

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