Where are we in the race for an HIV vaccine?

While progress in the race for effective COVID-19 vaccines has been rapid and impressive – with three vaccines so far proving to be effective based on preliminary data, an effective HIV vaccine remains elusive. This is at least in part because the HI virus is a much tougher nut to crack.

“Every vaccine I have done I have failed. It’s like asking me how long a piece of string is. It’s like asking me if we found the holy grail,” said Professor Glenda Gray, president of South African medical research. Council. “Every vaccine we have designed has not produced neutralizing antibodies. This is probably what you need to be effective against HIV.”

Professor Linda-Gail Bekker, Deputy Director of the Desmond Tutu HIV Center, says that the same unprecedented scientific stakeholders have not yet come to the development table to lend the best and best creative ideas for HIV in the same way. as it happened [for] COVID-19.

What is needed to make an HIV vaccine

To make a vaccine for HIV, Gray explains that we first need to know what immune response is needed, but since few people have ever been cured of HIV, it is difficult to make a vaccine because it is unclear what the vaccine should do exactly. . In other words, what kind of immune response should it cause in the body.

Understanding immunity is difficult, and although scientists have apparently been successful in creating a vaccine for COVID-19, the SARS-CoV-2 virus is much easier to break down than HIV, Gray says.

A vaccination works by providing our bodies with an immunogen, or a substance that indicates to our bodies to produce a specific immune response that targets the virus. Immunogens are developed on the basis of antigens, which are the parts of the virus to which our bodies have an immune response.

Gray explains that the antigen for SARS-CoV-2 is the field protein on the envelope of the virus, and since scientists have identified it, they may develop vaccines that may elicit a certain type of immune response to target these ear proteins. For SARS-CoV-2, these ear proteins are the most vulnerable parts of the virus. For HIV, however, the vulnerability of the virus is harder to find and is constantly changing, Gray says.

Bekker says that the MI virus can escape from the body’s innate immune response, which means that the virus has already mutated because the body creates antibodies, which makes the previously made antibodies useless, but is still effective in becoming a possible candidate for vaccine to remove.

How the viruses differ

The vein proteins for SARS-CoV-2 are on the envelope of the virus. Think of a ball as the envelope, and small sticks as the nails. Overall, SARS-CoV-2 has little defense.

For HIV, the viral envelope is armored with what Gray calls glycan shields, or small portions of sugar molecules, which make the virus very difficult to penetrate. Think of an armadillo, she adds, with tough protective scales. “HIV is constantly recurring, and the protected areas of the [viral] envelope is very difficult to reach and is usually covered [by glycan shields], so finding a part of the envelope that is constant, despite replication, and that is easy to access is a big challenge, “says Gray.

“The MI virus has evolved over time into a number of ways to stay in hiding mode and evade the human immune system,” Bekker adds. Regarding the glycan shields that cover the ‘antigen’ parts of the viral membrane, she says that the parts of the viral membrane, which would normally increase the immunity of a human host, are camouflaged.

“There’s a lot of effort, money, science and power unraveling the structure of HIV and trying to understand the envelope and the glycan shield and trying to find those vulnerable parts of HIV, and it’s a big effort,” he said. Gray.

Prevention of HIV infection through a vaccine

“To prevent a vaccine from preventing infection, it must block the very earliest infection that takes hold, so it requires immediate and very effective blocking of viral replication at the onset of infection,” explains Bekker.

To prevent or get rid of diseases, a vaccine should improve the immune system to help antiretroviral drugs (ARVs) reduce the replication of the virus. “If viral load is overcome or more strongly overcome, the disease will probably also be reduced.”

“No comparison”

Although worldwide progress in the development of a COVID-19 vaccine may be inspiring, it cannot be directly compared to HIV.

“For 30 years with the same platforms [or types of vaccines], we have never been able to elicit a neutralizing antibody response in the same way that you can get it with SARS-CoV-2 with the spike protein. There is no comparison, ‘says Gray.

‘We know it first [SARS-CoV-2] does not mutate at the same rate, and even if it does mutate, the ear protein does not change every few seconds, “she says. It’s like comparing a cat to a jaguar. It is a very different animal, even though it is a virus. ‘

mRNA vaccines for HIV?

Two of the first three COVID-19 vaccines showing signs of efficacy (the Moderna and Pfizer / BioNTech vaccines) use a newer vaccine technology using messenger RNA (these vaccines are called mRNA vaccines). This raises the question of whether mRNA vaccines can be used against HIV.

“It’s an interesting question,” Gray says.

‘They use the vein protein in the mRNA [vaccine] and it goes back to the issue if you can find an immunogen that is conserved by viral replication and that can be easily achieved. No matter what platform you use, for HIV, it’s not really the platform, it’s the immunogen that counts. The platform gets the immunogen into the body and helps you get an immune response. “Unless you have the right immunogen, you will not get the right response,” she says.

Antibodies are usually neutralized

Gray says scientists are watching how neutralizing antibodies develop in people who cause broader neutralizing antibodies. “We took the envelope of the virus at that stage when the antibody changed and identified the immunogens along the way to broader neutralizing antibodies. The idea is to take the immunogens and attract the immune system to cause the broader neutralizing antibodies. will protect people. ‘

She says the trick with HIV is to find the right immunogen that will train the immune system to make broader neutralizing antibodies, which will then deactivate the virus upon exposure.

Exciting vaccine trials underway

Gray and Bekker say there are currently four particularly striking HIV vaccine trials underway.

The Imbokodo study, which is ongoing in South and Southern Africa, is a preventative vaccine that contains immunogens from around the world, in other words, it contains immunogens from different strains of HIV from around the world. This study, which started in November 2017, includes only women and is in the follow-up phase. Imbokodo’s cousin trial, MOSAICO, is an experimental vaccination system that seeks to prevent HIV infection in men and / or transsexuals. This study is ongoing in the Americas.

The third and fourth studies that Gray and Bekker emphasize are both part of a larger study called AMP, or antibody-mediated prevention, or to give antibodies to humans to see if it provides protection. Bekker says that two AMP studies have currently been completed, and that the results will hopefully be before the end of the year.

“There is quite a rich pipeline of ideas for HIV vaccine trials in phase 1 and early phase 2. So we still have hope,” says Bekker.

As access to preventative therapies grows, such as pre-exposure prophylaxis (PrEP), Bekker says the design of vaccine trials is becoming more complicated. “In other words, since populations have access to PrEP, they may fortunately have a lower incidence of HIV, which makes the studies larger and more difficult to do. This is a good problem, but it means we need to be creative in “we design so that the studies are not impossible to do, and we can still move scientific research and development forward. This is an exciting time for prevention,” she emphasizes.

HIV research paved the way for other vaccines

While the search for Gray’s “holy grail” continues, research for an HIV vaccine has helped develop vaccines for other diseases, including COVID-19.

“COVID-19, Ebola and Zika [virus] benefited greatly from all the work done to develop HIV vaccine platforms, so if we had not invested all this money in HIV, we would not have had solutions for Ebola, Zika and SARS-CoV-2 . Because of those platforms, we were able to move fast, fast and fast to the next pathogen, ‘says Gray.

With COVID-19 taking center stage over the past year, global resources from both the public and private sectors have been drawn to create a vaccine.

Bekker says that we can see significant progress if the same amount of energy and resources are diverted to HIV.

“We have not seen the private industry involved in HIV and TB (tuberculosis) that we have seen with COVID-19. Presumably based on investment and return considerations. If we were to think so, speed and progress would increase logarithmically. be, “she says.

“[For the] the first time the HIV field finds new targets – to neutralize antibody targets – which neutralize new possibilities for the development of HIV vaccine or even passive transmission of antibodies in general (as done for COVID-19, and in the AMP studies ) which also offers new opportunities. The question remains whether we will be able to attract the scientific and financial resources to implement it. ‘


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