HIV vaccine candidate induces immune response in early clinical trials


In a phase 1 study, an experimental HIV vaccine has been found to induce broadly neutralizing antibody precursors in a small group of volunteers. The findings suggest that a two-dose vaccine regimen eight weeks apart can elicit an immune response against the human immunodeficiency virus.

Clinical trial results released Thursday on World AIDS Day science magazineestablishing a “clinical proof of concept” to support the development of boosted regimens to induce an immune response against HIV infection, which is incurable and can lead to acquired immunodeficiency syndrome, or AIDS.

The vaccine, called eOD-GT8 60mer, had a “favorable safety profile” and tested positive in 97 percent of 36 recipients at or without the disease, according to researchers at Fred Hutchinson Cancer Center’s Scripps Research Center. Broadly neutralizing antibody precursors were induced in all recipients except one, the National Institutes of Health and other institutions in the United States and Sweden.

antibodies are proteins produced by the immune system to help fight infection, and broadly neutralizing antibody Many genetic variants of HIV are known to neutralize, but they are difficult to induce through vaccination.

“Understanding how to induce broadly neutralizing antibodies against pathogens with high antigenic diversity, such as HIV, influenza, hepatitis C virus, or the betacoronavirus family, is a major challenge for rational vaccine design,” the researchers wrote. Germline-targeted vaccine design offers a potential strategy to address this challenge.”

The eOD-GT8 60mer vaccine candidate is germline targetingwhich means it is designed to induce the production of broadly neutralizing antibodies by targeting and stimulating the correct antibody-producing cells.

International AIDS Vaccine Initiative Announced Start of phase 1 clinical trial In 2018, the safety of eOD-GT8 60mer and its ability to induce immune responses were evaluated.

A total of 48 healthy adults, ages 18 to 50, were enrolled in the trial at two sites: George Washington University in Washington and Fred Hutchinson Cancer Center in Seattle.

Of the participants, 18 received a 20-microgram dose, followed by the same dose of vaccine and adjuvant eight weeks later, and 18 received a 100-microgram dose, followed by the same dose of vaccine and adjuvant eight weeks later. 12 people received two doses of a saline placebo, eight weeks apart. The adjuvant, called AS01B, was developed by pharmaceutical company GSK. The vaccine and placebo are injected into an arm muscle.

The researchers collected and analyzed immune cells in the participants’ blood and lymph nodes during the study. They specifically looked at how B cells, a type of white blood cell in the immune system that make antibodies, respond to vaccines.

The researchers found no serious adverse events were reported among the study participants, and no participants became HIV-infected during the study period. About 97% of the 48 study participants (or all but one participant) reported local or systemic adverse events that were generally mild or moderate, such as injection site pain, discomfort and headache. In most cases, these incidents are resolved within a day or two.

After the first immunization, all vaccine recipients but no placebo recipients were found to develop antibodies elicited by the eOD-GT8 60mer vaccine. Reactions to these vaccines increased after the second dose, the researchers wrote.

Another phase 1 study of the vaccine candidate is underway, said Dr. Julie McElrath, senior vice president and director of the Division of Vaccines and Infectious Diseases at the Fred Hutchinson Cancer Center, of which she is a co-author.

What makes this HIV vaccine candidate unique is that it was designed to directly target the production of broadly neutralizing antibodies, said Dr. Timothy Schacker, associate dean for HIV medical research and program director at the University of Minnesota School of Medicine, who was not involved in the study. .

“In HIV, when we designed and tested vaccines in the past, for whatever reason, they didn’t induce these broadly neutralizing antibodies,” he said. “Call them superantibodies, if you want. The broadly neutralizing antibodies work much more efficiently. They’re better at controlling things.”

By showing that the vaccine can induce broadly neutralizing antibodies, the new research could help develop other types of immunizations, not just HIV vaccines, Schacker said.

“The hope is that if you can induce this immunity in people, you can protect them from some of these viruses, and it’s very difficult for us to design effective vaccines,” he said. “So this is an important step forward.”

Dr. Carlos del Rio, co-director and executive vice dean of the Center for AIDS Research at Emory University, said that while this is “exciting science,” more work is needed before the vaccine can be considered for public use Grady Health System’s Emory School of Medicine, who was not involved in the new study.

“We know that broadly neutralizing antibodies are a potentially effective strategy for preventing HIV,” del Rio said. “We’re nowhere near using it as a vaccine, but it’s very exciting science.  …Investing in this type of research is not only critical to developing an HIV vaccine, but if the strategy works, it will Can be used in other vaccines.”

An HIV vaccine would likely need to elicit these broadly neutralizing antibodies, or bnAbs, “that recognize the globally diverse strains of HIV and could prevent HIV infection.” However, eliciting bnAbs through vaccination has so far proven impossible A key challenge is that bnAbs rarely develop, even during infection,” Penny Moore, Wits University and South Africa’s National Institute of Infectious Diseases, wrote in an editorial Published alongside the new research.

A “key question” that still needs to be answered is how long the antibodies elicited by the first immunization last.

Moreover, if the booster differs too much from the previous vaccine, “antibodies elicited by the first vaccination may not recognize the booster and may not mature further,” Moore wrote. “However, combining many different injectables into an HIV vaccine regimen is unattractive. Balancing the need for antibody maturation against bnAbs with real-world feasibility is critical.”

Last year, more than 38 million people worldwide were living with HIV or AIDS. More than 20 HIV vaccine clinical trials are underway worldwide, According to the International AIDS Vaccine Initiative.

In the United States, many people already resort to taking daily HIV preventive pills or frequent injections, called PrEPto reduce their risk of infection.

“It’s a daily pill, or a painful injection. It’s uncomfortable at best, and you have to inject it several times a year,” Shaq said of PrEP.

But having an HIV vaccine available would make protection against the virus more accessible, he said. “If you can provide a vaccine, you reach more people, and if you have an effective vaccine, you provide more and better coverage to reduce the likelihood of transmission when you are exposed.”

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