Why were the COVID vaccines achieved in months and there is still no one for HIV?

The first cases of AIDS were described in 1981 and it was not until 1983 that Luc Montagnier’s laboratory isolated and identified the virus that was wreaking havoc, the VIH. The first patients of COVID-19 They were those of Wuhan, in December 2019, and in a matter of days it was learned that SARS-CoV-2 was behind it.

Current cutting-edge technology and international scientific collaboration made it possible to immediately know “the identity” of the causative agent of COVID-19, for which there are already more than a dozen vaccines in the world. However, for HIV there is none, neither preventive nor therapeutic. Why? Where are the difficulties and barriers of a virus whose first cases appeared decades ago?

Although there have been many advances, today the only thing that works against the human immunodeficiency virus (HIV), in addition to protection to avoid contagion, is antiretroviral treatment.

“Our immune system is not well prepared to control HIV,” sums up José Alcamí, head of the AIDS Immunopathology Unit at the Carlos III Health Institute (ISCIII, in Spain).

In the case of coronavirus, the vast majority are cured because their immune system is able to recognize the virus and direct an antibody response to control the infection. Anti-COVID vaccines use different mechanisms to stimulate our immune system to respond to the virus in advance and produce the necessary elements – T and B lymphocytes – to fight it.

“But in the face of HIV we do not have a model to imitate because the immune system is incapable of controlling the infection,” says the ISCIII researcher: “What you copy is going to fail, that’s why you have to design vaccines that teach this system to work otherwise”.

The escape mechanisms of HIV

And why in one case the defenses know how to control the infection and in another not? The answer lies in the escape mechanisms of HIV.

This virus has a greater capacity to mutate, more than a thousand times higher than that of the coronavirus, and its envelope structure is different. The equivalent of the protein that SARS-CoV-2 uses to enter the cell (spike protein), in HIV it is a folded structure – the glycoprotein gp160 – that only opens to enter the cell.

This is important because the neutralizing antibodies that block the virus recognize the protein that is like an open hand on the spike of SARS-CoV-2, but “not the fist” of HIV, remarks Alcamí, who details that another of the problems of the AIDS virus is that its envelope is covered with sugars.

Sugars act as a shield and the antibodies produced by the immune system, even if they exist, fail to reach their target.

In addition, HIV has the ability to “hide”, it can infect the cell but remain off, without multiplying, as in the dock. This is called the viral dormancy state, and cells in this state are reservoirs. Antiretrovirals prevent the virus from replicating but cannot attack its latent form.

Moreover, in latency the virus is also capable of dividing the cell and each of the new cells carries the quenched virus in its DNA, which is a great obstacle to its cure and the development of vaccines.

Only one preventive phase III vaccine

The Johnson & Johnson (J&J) preparation is the only one currently in phase III – the last – of a clinical trial. His research was designed in two branches, the Imbokodo study, in African women, and the Mosaic, in men and transgender people from Europe and America.

The first, in phase 2b, was suspended last August for not showing sufficient protection. However, Janssen – J & J’s pharmaceutical division – decided to go ahead with Mosaico, which includes 3,800 volunteers in Argentina, Brazil, Italy, Mexico, Peru, Poland, Spain and the United States.

Vicente Estrada, head of the infectious diseases unit at Hospital Clínico San Carlos, in Spain, coordinates the trial at that center and, as detailed, the study has already begun.

Participants will receive four doses of the preventive vaccine to compare the rate of new diagnoses in the placebo arm versus those vaccinated. The results will not be before a year.

The trial, Estrada argues, is not exactly the same as that of Imbokodo: Mosaico’s vaccine has one more antigenic determinant; the genotype of HIV circulating in Africa is slightly different from that in the western world; and the volunteers this time are male (although the route of transmission is the same, there are some differences between men and women).

“These three factors suggest that Mosaico could offer protection that Imbokodo does not produce. In principle, there are high hopes for the efficacy of the vaccine, although unfortunately the African branch has been the first bad news ”, he says.

Other prototypes of preventive vaccines are underway. For example, the ISCIII, together with the Hospital Clínic de Barcelona (Spain), are leading a project that could begin the concept trial in phase I next year, with a small number of patients to test whether it induces antibodies.

This candidate, according to Alcamí, has “a quite original design”, belongs to a new and third generation of vaccines whose objective is to stimulate only those cells prepared to fight HIV that, although a minority, it is known which are: “it is not enough that the immune system reacts but you have to tell it and teach it how ”.

In addition, therapeutic vaccines are tested. Last March, the Spanish AIDS Research Institute IrsiCaixa announced that the HTI candidate of AELIX Therapeuitcs, achieved in phase I / IIa that 40% of the participants who received the preparation had better control of the virus when the antiretrovirals.

In combination with other drugs, it could help contain the virus without the need for permanent antiretroviral treatment.

Alcamí and Estrada agree that, although no vaccine has succeeded, what they have learned is essential to continue.

The ISCIII researcher affirms that there is a lot of research and very brilliant from a new conceptual point of view, “but still far from the clinical application or the phase III trial”.

For Estrada, even if the prototypes do not work, it is always a step forward, because “surely we will have the vaccine sooner or later”.