An experimental HIV vaccine has been found to induce broadly neutralizing antibody precursors 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 antibody precursors 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.
Inducing ‘super antibodies’
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.