An experimental HIV vaccine has been shown to induce broadly neutralizing antibody precursors among a small group of volunteers in a phase 1 study. The results suggest that a two-dose regimen of the vaccine, given at eight weeks of interval, may elicit immune responses against human immunodeficiency virus.
The results of the clinical trial, released Thursday on World AIDS Day in Science magazineestablish “clinical proof of concept” supporting the development of booster 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 antibody precursors in 97%, or all but one, of 36 recipients, according to Scripps Research researchers, the Fred Hutchinson Cancer Center, 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 have been difficult to obtain through vaccination.
“Learning to induce broadly neutralizing antibodies against pathogens with high antigenic diversity, such as HIV, influenza, the hepatitis C virus or the betacoronavirus family, represents a great challenge for the rational design of vaccines”, wrote the researchers. “Designing a germline-targeting vaccine offers a potential strategy to address this challenge.”
The eOD-GT8 60mer vaccine candidate is germline targetingmeaning 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 assess 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.
Of the participants, 18 received a 20-microgram dose of the vaccine and, eight weeks later, a similarly sized dose of the vaccine with an adjuvant; 18 received a 100 microgram dose of the vaccine and, eight weeks later, an equal 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 the placebo were administered into the arm muscle.
The researchers collected and analyzed immune cells from participants’ blood and lymph nodes during the study. They specifically looked at how B cells, a type of white blood cells that make antibodies in the immune system, responded to the vaccine.
Researchers found no reported serious adverse events among study participants, and no participants acquired HIV infection during the study. About 97% – or all but one – of the 48 study participants reported generally mild or moderate local or systemic side effects, 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 eOD-GT8 60mer vaccine-induced antibodies. These vaccine-induced responses increased after the second vaccination, the researchers wrote.
Another phase 1 study of this vaccine candidate is underway, said Dr. Julie McElrath, senior vice president and director of the division of vaccines and infectious diseases at Fred Hutchinson Cancer Center, who was one of the authors of the study.
What’s unique about this HIV vaccine candidate is that it was designed to directly target the production of broadly neutralizing antibodies, said Dr. Timothy Schacker, associate dean of research and director of the HIV Medicine program at the University of Minnesota Medical School, who was not involved in the research.
“In the case of HIV, when we’ve designed and tested vaccines in the past, they for some reason didn’t induce these broadly neutralizing antibodies,” he said. “Call them super antibodies, if you will. Broadly neutralizing antibodies work more effectively. They are 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 that kind of immunity in people, you can protect them from some of these viruses that we’ve had a very hard time designing effective vaccines for,” he said. “So this is an important step forward.”
Although this is “exciting science”, there is still a lot of work to be done before this vaccine can be considered for public use, said Dr. Carlos del Rio, co-director of the Center for AIDS Research at Emory University and Executive Vice Dean. for Grady Health System’s Emory School of Medicine, which 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 are a long way from using it as a vaccine, but it is very exciting science. … Investing in this type of research is critically important not only for developing an HIV vaccine, but if this strategy works, it can be used for other vaccines.
An HIV vaccine will likely need to elicit these broadly neutralizing antibodies, or bnAbs, “which are able to recognize various strains of HIV globally and can prevent HIV infection. However, triggering bnAbs by vaccination has proven impossible so far. A major challenge is that bnAbs rarely grow, even during infection,” said Penny Moore, of the University of the Witwatersrand and the National Institute of Communicable Diseases in South Africa. written in an editorial published alongside the new study.
A “key question” that still needs to be answered is how long the antibodies produced by the first vaccination can last.
Additionally, if the booster is too different from the previous vaccine, “antibodies that were triggered by the first vaccination may not recognize the booster and will not mature further,” Moore wrote. “However, incorporating many different vaccines into an HIV vaccination regimen is unattractive. It will be critical to strike the right balance between the need for antibody maturation to bnAbs and real-world feasibility.
Last year, more than 38 million people were living with HIV or AIDS worldwide. More than 20 HIV vaccine clinical trials are underway worldwide, 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 PrEPto reduce their risk of infection.
“It’s a daily pill or it’s a painful blow. It’s a shot that’s uncomfortable at best and one that you need to get several times a year,” Schacker said of PrEP.
But the availability of an HIV vaccine would make protection against the virus more accessible, he said. “If you can administer a vaccine, you are going to reach more people and provide, if you have an effective vaccine, greater and better coverage to reduce the likelihood of transmission if you are exposed.”