The AIDS vaccine: Is there hope?

by time news

When we give a talk about the AIDS vaccine, the most frequent question is: How has it been possible to manufacture a vaccine against covid-19 in less than a year? and that after four decades we still don’t have any for HIV? In addition to feeling a little awkward, we try to explain that the two viruses cannot be compared. That HIV represents a completely new challenge in the field of vaccines.

Jose Alcami Pertejo

  • Research Professor. Director of the AIDS Immunopathology Unit. Virology-Immunology, Carlos III Health Institute

First of all, let’s make clear what a vaccine is: we are talking about a biological simulation in which we confront our immune system with the false microbe attack. Thanks to this simulation, our system is activated and stores in its memory the germ with which we have vaccinated. When we later face the actual infection, the already trained system remembers, recognizes and eliminates the microbe.

A succession of failures

In the case of vaccines that have been developed against HIV, we can distinguish three stages.

Initially, prototypes similar to those of classic vaccines were used against other viruses such as polio and hepatitis B. These immunizations induce antibodies, biological missiles that block viruses before they enter our cells. Faced with its failure, in a second stage it was sought to induce responses called cellular, the infantry that destroys infected cells. Also these prototypes failed.


A woman scratching her eyes

In the third stage, both strategies were combined: vaccines that induced antibodies and cellular responses. In only one of these trials, the RV144 (made in Thailand), a positive result was achieved. But it was insufficient: only 30% of the vaccinated subjects achieved protection, when the minimum required is 50%. Furthermore, it was not replicated when a similar trial was conducted in South Africa.

UNAIDS, UNICEF and WHO launch a new global partnership to end AIDS in children by 2030
UNAIDS, UNICEF and WHO launch a new global partnership to end AIDS in children by 2030
4421010037/iStockphoto

We can say that HIV has left the history of vaccines strewn with corpses with names of clinical trials. Recently suspended due to its lack of efficacy, the Janssen company’s Mosaic study was the last. There are no further phase III trials planned.

Why have we failed?

The biggest limitation to getting the vaccine is that our immune system is not prepared to deal with HIV. It is easy to understand with an example. What happens when we get infected with covid? If we are not among the 1% of deceased, 99% of those affected will be cured because our immune system eliminates the virus in a few days. In contrast, out of 100 people infected with HIV, none is capable of eliminating the virus. In the absence of treatment, 99 of those 100 will die of AIDS.


stock image of cheeses

We are therefore facing a new challenge: teaching the immune system to do something that it does not know how to do naturally. It is not enough to arouse the response as traditional vaccines do, because that reaction does not work. You have to instruct the immune system to do something new that is effective.

What makes HIV so resistant to the immune response?

Evolution has provided HIV with a devilish shell, or casing. Coat proteins are found on the surface of viruses and allow them to infect cells by binding to cell receptors. A vaccine is effective only if it induces antibodies that block these proteins, preventing the entry of the virus. They are called neutralizing antibodies. The HIV envelope evades these antibodies by four mechanisms.

Laboratory of the AIDS group of the Clinical Hospital-IDIBAPS
Laboratory of the AIDS group of the Clinical Hospital-IDIBAPS
Europa Press

It forms an inaccessible closed structure. Imagine that the antibodies are directed at the fingers of one hand. The envelope of SARS-CoV-2 it is an open hand whose fingers are easy to reach, whereas HIV’s is a clenched fist that only opens when it touches the cell membrane. Too late for the antibodies to reach their target.

Like the shield of the star wars ships, HIV Coats Its Coating With Sugars that block the arrival of antibodies to its surface. It is like a lollipop that protects the chocolate core inside.

In the outer areas, accessible to antibodies, the highly variable envelope protein mutates and escapes attack.


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Added to these limitations is the fact that our immune system is slow against HIV. It takes two years to generate potent antibodies, and in that time the virus generates resistant variants. In the race between the antibodies and the envelope, HIV runs much faster.

The real-life difficulties of testing vaccines

Added to the technical difficulty of obtaining a vaccine prototype with the possibility of success is the difficulty of investigating the efficacy of these prototypes in clinical practice. This is basically due to three reasons:

The attack rate (new infections) is lowTherefore, cohorts of thousands of patients are required, which must be followed up for years to find significant differences between the vaccinated group and the placebo.

Vaccines should be evaluated in populations most likely to be infected, such as those in the sub saharan africaplaces with fragile sanitary structures.

From an ethical point of view, participants must be offered and reminded that they have to use protection measures, condoms… This reduces the number of infections and makes it more difficult to obtain differences between groups.

Is there any good news?

Although it may seem hard to believe, there is good news.

First, despite its secrecy, we have found tiny cracks in the HIV envelope. Some very special antibodies, which we call “broadly neutralizing”, they can reach those Achilles heels of the virus and block it.

Although very rare, these antibodies exist and are produced by some patients. Since we know the exact area of ​​the HIV envelope they are targeted at, we can modify and tune it to generate vaccines that induce these antibodies.

Health launches the 'Live Positive' campaign on the occasion of World AIDS Day
Health launches the ‘Live Positive’ campaign on the occasion of World AIDS Day
20M EP

The ultimate challenge is producing those antibodies quickly. This can be done by sequential immunization with different variants of the envelope protein. Through this strategy we accelerate the maturation of the antibodies produced by the immune system.

Mission Impossible?

We need vaccines capable of activating the few cells that produce those exceptional antibodies capable of crossing the barriers of the virus and reaching their Achilles heels. Powerful antibodies, capable of neutralizing hundreds of variants and that must be produced in weeks instead of taking years to generate. They are completely new vaccines against a new problem, of high technological design. The SARS-CoV-2 vaccine is a walk compared to HIV, a summit of enormous difficulty.


A woman prepares a bowl of cereal with milk for breakfast.

In 2020, 1.5 million people became infected with HIV and 680,000 died of AIDS. The virus is there, and it continues to kill. Developing a vaccine is the only way to kill it. As difficult as it is, we have to keep trying. In his book The Art of War, Yun-Tzu says: “If you know your enemy and yourself, you should not fear the outcome of a thousand battles. If you don’t know either the enemy or yourself, you will lose every battle.”

Now, thanks to our failures, we know our weaknesses and the enemy’s strengths. Perhaps for the first time we have a chance to win with the new generations of designer vaccines that we are working on.

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