The first induction of bnAb precursor molecule production against HIV by vaccination in humans

It is widely assumed that for an HIV vaccine to be broadly effective, it must stimulate the body to develop antibodies known as broadly neutralizing antibodies (bnAb) capable of neutralizing a variety of HIV strains. Scientific research has now advanced significantly in this direction.

In a new preliminary study, researchers from the National Institute of Allergy and Infectious Diseases, the Scripps Research Institute, the Fred Hutchinson Cancer Research Center, and the University of Washington, among other research institutes, found that an experimental HIV vaccine was able to induce human immune system response necessary to produce bnAb against HIV. This is the first time a vaccine has been shown to do this in humans. The findings were published in the Dec. 2, 2022 issue of Science titled "Vaccination induces HIV broadly neutralizing antibody precursors in human".

The new trial included 48 healthy adults who were randomly assigned to receive either two doses of an experimental HIV vaccine or two doses of a placebo (inactive substance). The experimental HIV vaccine resulted in a considerable increase in immune cells called B cells, which create bnAb precursor molecules against HIV in 35 of the 36 individuals. This accomplishment serves as "proof of concept" that a vaccine has the ability to elicit such a response.

"This is obviously an encouraging finding," said Dr. Colleen Kelley, an associate professor at Emory University School of Medicine who was not involved in the study, "but there's still a lot of research to be done." According to Kelley, the initial step is to induce these B cells to generate. The main question right now is whether these bnAb precursor molecules can be stimulated to mature into bnAb antibodies.

Since the 1980s, scientists have been trying to develop an HIV vaccine, with occasional glimmers of hope followed by disappointment. HIV is a formidable enemy for many reasons—not the least of which is its ability to mutate rapidly, producing new strains of the virus as it is passed from one person to another.

"Traditional vaccines against viral diseases such as measles, influenza, or COVID-19 work by stimulating the immune system to produce antibodies against the virus, which do not work against HIV," Kelley explained, "and vaccines that successfully produce antibodies were developed, but these antibodies do not stop HIV infection." Dr. Juliana McElrath, co-corresponding author of the paper and a professor at the Fred Hutchinson Cancer Research Center, said, "We haven't been able to develop an HIV vaccine because it's really hard to do."

The experimental HIV vaccine tested in this new study is eOD-GT8 60mer which utilizes an engineered immunogen to elicit an immune response. It is designed to stimulate and expand certain rare B cells that have the potential to produce antibodies against HIV's bnAb.

There were no safety concerns among the 36 participants who received this investigational HIV vaccine. All but one demonstrated the immunological response that the authors were hoping for, which McElrath and Kelley both agreed is an essential step. However, it is merely the first stage in a lengthy process.

These researchers are now starting another small clinical trial in healthy volunteers, this time using eOD-GT8 60mer followed by a booster vaccination with a different immunogen to try to drive the maturation of the bnAb precursor molecules even further.

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