How close are we to an HIV vaccine?

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(Mexico) Despite the considerable progress made in the treatment and prevention of HIV / AIDS in recent decades, an effective vaccine remains inaccessible, even if it is absolutely essential to end the global pandemic, which kills more than 700,000 people each year.AIDS is caused by the human immunodeficiency virus (HIV) and is one of three major diseases that affect people in developing countries, with tuberculosis and malaria.

According to the World Health Organization (WHO), 37.9 million people worldwide live with the disease, of which 23.3 million have access to antiretroviral therapy (ART), the best treatment currently available.

This represents an increase of 2.3 million people on antiretroviral therapy since 2016, according to data updated globally by UNAIDS, in 2018. But the organization warns that "the extension of access treatment must not be taken for granted ".

"The only way to control or eliminate a disease is to use a vaccine. A vaccine will cost less than any other intervention and we need it because we are still not close to controlling HIV. "

Glenda Gray, President of the South African Medical Research Council, the South African Medical Research Council.

The problem is that new infections appear all the time: at least 1.7 million more each year, of which 160,000 are children under 15 years old.Glenda Gray, chair of the Medical Research Council of South Africa (SAMRC), told SciDev.Net that "the only way to control or eliminate a disease is to use a vaccine. A vaccine will cost less than any other intervention and we need it because we are still not close to controlling HIV. We are missing all the milestones at the global and local levels. "

Larry Corey, senior researcher at the HIV Vaccine Test Network (HVTN), points out the scale of the global epidemic.

"HIV is still the pandemic of our time. 5,000 people are infected every day, "he says. Researchers such as Larry Corey have been working on developing an HIV vaccine since the 1980s, and while significant progress has been made, there is still no viable protection that can be extended to HIV. global scale.

Why is it so difficult to find a vaccine that works?

The most effective vaccines use antibodies to neutralize viral infections. Scientists, however, found that it did not work for HIV because the virus reproduced and mutated too quickly for the antibodies to be effective. In addition, research has shown that there are different subtypes of HIV distributed around the world: while subtype B is widespread in North America and Europe, subtype C prevails in southern and eastern Africa. .

The virus has also evolved to be able to "hide" in cells apparently free of infection, thus suppressing immune responses at an early stage of the disease.

In addition, adds Glenda Gray, her genetic diversity is greater than any other pathogen known to date.

"HIV is a very difficult virus," says Larry Corey, expert in virology. "It is masked so never seen in a virus. He is very intelligent and uses different mechanisms to evade the immune system and persist. It is more effective than any other virus.

"Although animal models have been widely used to research the effectiveness of vaccines, they are generally expensive and do not guarantee that the drugs will work in humans. Because of its genetic diversity, the HIV virus can cause persistent infections that our immune system is unable to fight. A vaccine must do a lot better than our body. "

Research has focused on understanding the types of immune responses to be produced to win the battle against the disease.

The idea is to work with antibodies that can identify and attack the virus before it largely infects the body. In other words, what are the most vulnerable aspects of the virus that a vaccine can work on to be effective.

There is no human model to cure HIV, which is an additional barrier. "One of the reasons we have not had a vaccine is that no human being has ever been cured of HIV," says Larry Corey. "Zero on 72 million. For every infectious disease, at least some people treat themselves, but this is not the case with HIV. "

Where are we now ? Essays and promises

Large-scale clinical trials testing the efficacy of an HIV vaccine began to yield results in 2003, and although no vaccine is yet available, significant progress has been made.

Of the more than 100 vaccines that have been tested in humans, the biggest success to date is the RV144 trial, also known as the "Thai study".

The research showed promising early results from an experimental vaccine, but the success was partial: participants were 60% less likely to be infected within a few months of vaccination, but this percentage dropped to 50% after three and a half years.

Linda-Gail Bekker, former president of the International AIDS Society, told SciDev.Net: "It is important to note that vaccination can be done … the Thai vaccine has taught us that. We have also found ways to secure and create antibodies that very effectively neutralize and bind to the virus. "

A modified version of the Thai vaccine is being tested in a large-scale phase 3 study in southern Africa. It is hoped that this will reduce the risk of infection by at least 50% and extend its period of protection.

The results will be made public by 2021. Another promising advance was announced in July, at the 10th International AIDS Conference, in Mexico City: the "Mosaico" vaccine, so called because it is composed of different strains. of the virus.

This vaccine has been shown to be effective in tests involving African women and will be evaluated more in men who have sex with men (MSM) and transgender populations in the United States, Argentina, Brazil, Italy. , Mexico, Peru, Poland and Spain.

"Mosaico is the best vaccine we've seen to protect animals. We now have to see if it works in humans, "says Larry Corey.

Linda-Gail, deputy director of the Desmond Tutu HIV Center, believes this vaccine should have a global impact if it works. Mosaico's researchers are cautiously optimistic about this new "global" vaccine, but others said expectations should be tempered because the virus has proven to be very dynamic and able to change quickly, avoiding all immune responses.

According to Larry Corey, another solution in case Mosaico does not work is to use identical monoclonal antibodies to determine if it works better than the Mosaico approach.

"We're going to look at the data and see if it's one or the other, or if it's a bit of both. So we have an alternative approach, "he adds.

A recent editorial of Nature concludes, "Ultimately, only efficacy studies will determine whether any of these promising concepts are capable of reducing infection rates or pre-existing levels of infection. But the pipeline of early-stage clinical studies and the accelerated pace of translation into clinical phase studies are very encouraging developments. "

The future of HIV

Finding at least one partially effective vaccine remains critically important for the HIV response.

According to the World Organization for Sexual Health Avert, the largest reduction in new infections would be achieved through a combination of pre-exposure oral prophylaxis (PrEP), universal antiretroviral therapy for people already living with HIV, and a vaccine.

"An HIV vaccine is a more realistic prospect today than it was ten years ago, and an optimistic forecast of HIV vaccine availability is that it may be available by 2030," he said. organization on its website.

Although HIV research has always received more funding than any other infectious disease, various experts have warned that permanent investments are under threat.

"Almost all vaccine innovations are in the public sector; pharmaceutical and biotechnology companies stay away, "said Glenda Gray.

"It's a very risky business and the companies have been running away from it," says Larry Corey.

The Mosaico study, a public-private partnership sponsored primarily by Janssen Vaccines & Prevention, is funded by the US National Institute of Allergy and Infectious Diseases (NIAID) and supported by the HVTN, whose headquarters is at the Fred Hutchinson Center for Cancer Research in Seattle, which facilitates its implementation.

According to estimates by Larry Corey, the largest investment in vaccine research in the United States receives $ 700 million a year from the government and $ 250 million from the Bill & Melinda Gates Foundation.

"It really is the US government and philanthropic organizations that have put their weight in the balance so that we reach a point where at least there is a sense of optimism about the possibility of developing a vaccine against HIV, "he says.

UNAIDS has said it is urgent to intensify HIV vaccine research. "Over the past decade, investments have remained stable at around $ 900 million a year, which is less than 5% of the total resources needed for the AIDS response," the group said in a statement. 2018.

"By increasing investment in HIV vaccine research, diversifying funds and attracting the best scientists from around the world, we could make an HIV vaccine a reality. "



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