Experts agree that a vaccine is the only way to stop a global pandemic that kills more than 700,000 people every year.
CECILIA ROSEN (SCIDEV.NET)
Mexico City 10 SEP 2019 – 00:03 CEST
The HIV virus reproduces and mutates too quickly for antibodies to be effective.
Despite enormous advances in the treatment and prevention of HIV/AIDS in recent decades, an effective vaccine remains elusive and is urgently needed to end this global pandemic that kills more than 700,000 people every year.
AIDS is caused by the human immunodeficiency virus (HIV) and is one of the three major diseases affecting people in developing countries, along with tuberculosis and malaria. According to the World Health Organization (WHO), 37.9 million people worldwide are living with HIV, and of these, 23.3 million have access to antiretroviral therapy (ART), the best treatment currently available. This represents an increase of 2.3 million people receiving ART since 2016, according to UNAIDS' 2018 global update. But the WHO warns that "increased access to treatment should not be taken for granted."
The problem is that new infections are appearing all the time: at least 1.7 million more each year, 160,000 of which are in children under 15. Glenda Gray, president of the South African Medical Research Council (SAMRC), explains to SciDev.Net: “The only way to control or eliminate a disease is with a vaccine. A vaccine will be cheaper than any other intervention, and we need one because we are still no closer to controlling HIV. We are not meeting all the targets, either globally or locally.”
The problem is that new infections are appearing all the time: at least 1.7 million more each year, of which 160,000 are in children under 15 years old
Larry Corey, the lead researcher for the HIV Vaccine Trials Network (HVTN), emphasizes the scale of the global epidemic. “HIV remains the pandemic of our time; 5,000 people are infected every day,” he notes.
Researchers like Corey have been working on developing an HIV vaccine since the 1980s, and although significant progress has been made, there is still no protection that works and can be distributed worldwide.
Why is it so difficult to find a vaccine?
Most effective vaccines use antibodies to neutralize viral infections. But scientists have found that this doesn't work with HIV because the virus replicates and mutates too rapidly for antibodies to be effective. Research has also shown that different HIV subtypes are widespread: while subtype B is common in North America and Europe, subtype C predominates in southern and eastern Africa.
Furthermore, the virus has evolved and is able to hide inside cells that are seemingly uninfected, suppressing immune responses in the early stages of the disease. Gray adds that, moreover, its genetic diversity is greater than that of any other pathogen known to date.
“HIV remains the pandemic of our time; 5,000 people are infected every day.”
“HIV has been a very difficult virus,” says Corey, a virology expert. “It hides better than any other virus we’ve ever seen. It’s very clever and uses various mechanisms to evade the immune system and avoid disappearing. It’s more effective than any other virus.”
Although animal models have been widely used to investigate vaccine efficacy, these models are typically expensive and do not guarantee that the drugs will work in humans. The HIV virus, due to its genetic diversity, can cause persistent infections that our immune system is unable to fight, so a vaccine must perform much better than our bodies.
The research has focused on understanding what kind of immune responses need to occur to win the battle against the disease. The idea is to work with antibodies that can identify and attack the virus before it infects the body as a whole. In other words, it's about identifying the virus's weak points that a vaccine can target to be effective.
There are no human models demonstrating that a cure for HIV exists, and that's yet another obstacle. “One of the reasons we haven't developed a vaccine is that no human being has ever been cured of HIV,” Corey explains. “Zero out of 72 million. With every other infectious disease, there are at least a few people who cure themselves, but that's not the case with HIV.”
The trials and their promises
Large clinical trials to test the effectiveness of HIV vaccines began to yield results in 2003, and although there is still no vaccine ready, significant progress has been made.
More than 100 vaccines have been tested in humans, and the most significant achievement to date is the RV144 trial, also known as the “Thai study.” The research showed promising initial results for an experimental vaccine, but its success was only partial: participants were 60% less likely to become infected in the first few months after 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: “The important thing is that we know it can be done [a vaccine]… The Thai vaccine has taught us that. Now we have also discovered ways to obtain and create antibodies that can bind to the virus and neutralize it very effectively.”
A modified version of the Thai vaccine is being tested in a large-scale phase 3 trial in southern Africa and is expected to reduce the risk of infection by at least 50% and extend the period of protection. Results are expected to be published around 2021.
Another recent and promising breakthrough was announced in July at the 10th International AIDS Conference in Mexico City: the Mosaic vaccine, so named because it is composed of different strains of the virus. The vaccine has proven effective in trials with women in Africa and will be further studied in men who have sex with men (MSM) and in transgender populations in the United States, Argentina, Brazil, Italy, Mexico, Peru, Poland, and Spain.
Mosaico is the best vaccine we've seen for protecting animals. Now we have to see if it works in humans,” Corey says.
Bekker, deputy director of the Desmond Tutu Center for HIV, believes this vaccine should have a global impact if it works. While Mosaico researchers are cautiously optimistic about this new “global” vaccine, others have said expectations should be tempered because the virus has proven to be highly dynamic and capable of rapidly mutating, evading all immune responses.
Corey believes that if Mosaico doesn't work, an alternative could be using identical monoclonal antibodies to see if they perform better than the strategy used with this vaccine. “We're going to analyze the data to see if it's one or the other, or if it could be a bit of both. So, we have an alternative approach,” he adds.
A recent editorial in Nature concludes: “Ultimately, only efficacy studies will determine whether any of these promising concepts are capable of reducing infection rates or pre-existing infection levels. But the development of early-stage clinical trials and the accelerated pace of implementation in treatment centers are very promising developments for this field.”
The future of HIV
Finding at least a partially effective vaccine remains crucial to the HIV response. According to Avert, a global sexual health charity, the best way to reduce new infections would be through a combination of oral pre-exposure prophylaxis (PrEP), universal antiretroviral treatment for people already living with HIV, and a vaccine. “The prospect of an HIV vaccine is more realistic than it was a decade ago, with the most optimistic forecasts predicting that a vaccine could be available by 2030,” the organization states on its website.
Although HIV research has historically received more funding than any other infectious disease, various experts have warned that this investment is under threat. “Almost all vaccine-related innovations occur in the public sector; pharmaceutical and biotechnology companies remain on the sidelines,” Gray says.
“HIV hides better than any other virus we have ever seen. It is very clever and uses different mechanisms to evade the immune system and not disappear. It is more effective than any other virus.”
“It’s a very risky business, and therefore companies have given up on it,” Corey adds. One exception has been the Mosaico study, a public-private collaboration primarily funded by Janssen Vaccines & Prevention, with funding from the National Institute of Allergy and Infectious Diseases of the U.S. National Institutes of Health and supported by HVTN, based at the Fred Hutchinson Cancer Research Center in Seattle, which facilitates its application.
According to Corey's calculations, the United States, the largest investor in vaccine research, receives $700 million annually from the government and $250 million from the Bill & Melinda Gates Foundation. "The U.S. government and philanthropy have been the biggest contributors to reaching a point where there is at least some optimism that an HIV vaccine can be developed," he says.
According to UNAIDS, there is an urgent need to increase research to find a vaccine for HIV. “Over the past decade, investments have remained constant at approximately $900 million per year, which is less than 5% of the total resources needed to tackle AIDS,” it stated in a 2018 declaration.
"A vaccine for HIV could become a reality if investments in research were increased, funding was diversified, and the best scientists from around the world were attracted."
From: https://elpais.com/elpais/2019/09/03/ciencia/1567504803_488840.html