Why COVID vaccines were developed in months, but there is still no HIV vaccine

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 causing havoc, HIV. The first Covid-19 patients were in Wuhan in December 2019, and within days it was discovered that SARS-CoV-2 was behind it.

Cutting-edge technology and international scientific collaboration made it possible to quickly determine the “identity” of the agent causing 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), apart from protection against infection, is treatment with antiretrovirals. “Our immune system is not well prepared to control HIV,” José Alcamí, head of the AIDS Immunopathology Unit at the Carlos III Health Institute (ISCIII, in Spain), told Efe.

In the case of the coronavirus, the vast majority manage to recover because their immune system is able to recognize the virus and direct an antibody response to control the infection. 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 when it comes to HIV, we don’t have a model to imitate because the immune system is incapable of controlling the infection,” says the ISCIII researcher: “Whatever you copy will fail, so we need to design vaccines that teach this system to work in a different way.”

HIV escape mechanisms

And why do the immune system control the infection in one case and not in the other? The answer lies in HIV’s escape mechanisms.

This virus has a greater capacity to mutate, more than a thousand times greater 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 looks like an open hand on the spike of SARS-CoV-2, but “not the fist” of HIV, Alcamí points out, who explains that another problem with the AIDS virus is that its envelope is covered in 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 cells but remain inactive, without multiplying, as if in a dugout. This is called viral latency, and cells in this state are reservoirs. Antiretrovirals prevent the virus from replicating but cannot attack its latent form.

Furthermore, in latency, the virus is also capable of dividing the cell and each of the new cells carries the deactivated virus in its DNA, which represents a major obstacle to its cure and the development of vaccines.

There is only one preventive vaccine in phase III

Johnson & Johnson’s vaccine is the only one currently in Phase III – the last phase – of clinical trials. Its research was designed in two branches, the Imbokodo study, in African women, and the Mosaico study, 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 – a division of Johnson & Johnson – 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 the San Carlos Clinical Hospital in Spain, is coordinating the trial at that center and, as he told Efe, the study has already begun.

Participants will receive four doses of the preventive vaccine to compare the rate of new diagnoses in the placebo group versus those vaccinated. Results will not be available for another year.

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

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

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

According to Alcamí, this candidate has “a fairly original design” and belongs to a new and third generation of vaccines whose objective is to stimulate only those cells prepared to fight HIV, which, although they are a minority, are known: “it is not enough for the immune system to react, but it must be told and taught how.”

Therapeutic vaccines are also being tested. Last March, the Spanish AIDS Research Institute IrsiCaixa announced that AELIX Therapeutics’ HTI candidate achieved better control of the virus in Phase I/IIa in 40% of participants who received the preparation when their antiretrovirals were temporarily withdrawn.

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 achieved this, what has been learned is essential to continue.

The ISCIII researcher says that there is a lot of very brilliant research from a novel conceptual point of view, “but still far from clinical application or phase III trials.”

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

(with information from EFE)

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