An experimental HIV vaccine has been found to induce broadly neutralizing antibodies among a small group of volunteers in a Phase 1 study. The findings suggest that a two-dose regimen of the vaccine, given eight weeks apart, can elicit immune responses against the human immunodeficiency virus.
The clinical trial results, published Thursday on World AIDS Day in the journal Science, establish “clinical proof of concept” in support of developing boosting regimens to induce immune responses against HIV infection, for which there is no cure and which can cause acquired immunodeficiency syndrome, known as AIDS.
The vaccine, called eOD-GT8 60mer, had a “favorable safety profile” and induced broadly neutralizing antibodies in 97%, or all but one, of the 36 recipients, according to the researchers from Scripps Research, the Fred Hutchinson Cancer Center, the National Institutes of Health and other institutions in the United States and Sweden.
Antibodies are proteins made by the immune system to help fight infections, and broadly neutralizing antibodies are known to neutralize many genetic variants of HIV, but they have been difficult to elicit by vaccination.
“Learning how to induce broadly neutralizing antibodies against pathogens with high antigenic diversity, such as HIV, influenza, hepatitis C virus, or the family of betacoronaviruses, represents a grand challenge for rational vaccine design,” the researchers wrote. “Germline-targeting vaccine design offers one potential strategy to meet this challenge.”
The eOD-GT8 60mer vaccine candidate is germline-targeting, meaning it was designed to induce the production of broadly neutralizing antibodies by targeting and stimulating the right antibody-producing cells.
The International AIDS Vaccine Initiative announced the start of this Phase 1 clinical trial in 2018, to evaluate the safety of eOD-GT8 60mer and the immune responses it is able to induce.
The trial included a total of 48 healthy adults, ages 18 to 50, who were enrolled at two sites: George Washington University in Washington and Fred Hutchinson Cancer Center in Seattle.
Among the participants, 18 received a 20-microgram dose of the vaccine and, eight weeks later, a same-size dose of the vaccine with an adjuvant; 18 received a 100-microgram dose of the vaccine and, eight weeks later, a same-size dose of the vaccine with an adjuvant; and 12 received two doses of a saline placebo, eight weeks apart. The adjuvant is called AS01B, developed by the pharmaceutical company GSK. The vaccines and placebo were given into the arm muscle.
The researchers collected and analyzed immune cells from the blood and lymph nodes of participants during the study. They specifically examined how B cells, a type of white blood cell that makes antibodies in the immune system, responded to the vaccine.
The researchers found no serious adverse events reported among the study participants, and no participants acquired HIV infection during the study. About 97% – or all but one – of the 48 study participants reported local or systemic adverse events that were generally mild or moderate, such as pain at the injection site, malaise and headache. In most cases, these events were resolved within a day or two.
After the first immunization, all vaccine recipients but no placebo recipients were found to produce antibodies elicited by the eOD-GT8 60mer vaccine. Those vaccine-induced responses increased after the second vaccination, the researchers wrote.
Another Phase 1 study on this vaccine candidate is underway, said Dr. Julie McElrath, senior vice president and director of the vaccine and infectious disease division at Fred Hutchinson Cancer Center, who was an author of the study.
What is unique about this HIV vaccine candidate is that it was engineered to directly target the production of broadly neutralizing antibodies, said Dr. Timothy Schacker, vice dean for research and program director in HIV medicine at the University of Minnesota Medical School, who was not involved in the research.
“In HIV, when we’ve designed and tested vaccines in the past, they didn’t for whatever reason induce these broadly neutralizing antibodies,” he said. “Call them super antibodies, if you want. The broadly neutralizing antibodies work more efficiently. They’re better at controlling things.”
By showing that broadly neutralizing antibodies can be induced by a vaccine, this new study could help inform the development of other types of immunizations, not just HIV vaccines, Schacker said.
“The hope is that if you can induce this kind of immunity in people, you can protect them from some of these viruses that we’ve had a very hard time designing vaccines for that are effective,” he said. “So this is an important step forward.”
Although this is “exciting science,” much more work needs to be done before this vaccine may be considered for use in the public, said Dr. Carlos del Rio, co-director of the Center for AIDS Research at Emory University and executive associate dean for Emory School of Medicine at Grady Health System, who was not involved in the new study.
“We know that broadly neutralizing antibodies are a potentially effective strategy to prevent HIV,” del Rio said. “We’re far from using this as a vaccine, but this is very exciting science. … Investing in this kind of research is critically important in not only developing a vaccine for HIV, but if this strategy works, it can be used for other vaccines.”
An HIV vaccine will probably need to elicit these broadly neutralizing antibodies, or bnAbs, “which are able to recognize globally diverse HIV strains and can prevent HIV infection. However, triggering bnAbs by vaccination has proven impossible so far. A key challenge is that bnAbs rarely develop, even during infection,” Penny Moore, of the University of the Witwatersrand and the National Institute for Communicable Diseases in South Africa, wrote in an editorial published alongside the new study.
A “key question” that still needs to be answered is how long the elicited antibodies from the first immunization can last.
Also, if the booster shot is too different from the previous vaccine, “antibodies that have been triggered by the first vaccination may not recognize the booster and will not mature further,” Moore wrote. “However, the incorporation of many different shots into an HIV vaccine regimen is unappealing. Getting the balance right between the need for antibody maturation toward bnAbs and feasibility in the real world will be essential.”
Last year, more than 38 million people were living with HIV or AIDS around the globe. More than 20 HIV vaccine clinical trials are ongoing around the world, according to the International AIDS Vaccine Initiative.
Many people in the United States have turned to daily HIV-prevention pills or frequent injections, known as PrEP, to reduce their risk of infection.
“It’s a daily pill or it’s a painful shot. It’s a shot that is uncomfortable at best that you have to get several times a year,” Schacker said of PrEP.
But having an HIV vaccine available would make protection against the virus more accessible, he said. “If you can give a vaccine, you’re going to reach more people and provide, if you have an effective vaccine, more and better coverage to reduce the probability of transmission if you’re exposed.”