Researchers Suggest That Engineering Specific B Cell Response Could Make the First HIV Vaccine Possible

A large collective of researchers may be one step closer to developing a vaccine against HIV after engineering a protein that triggers a widespread antibody response.

Scientists have identified promising broadly neutralizing antibodies (bnAbs) that could be used to create a vaccine against HIV, according to a study conducted by Scripps Research, IAVI, the Ragon Institute, and Moderna, Inc.

Human genes make bnAbs, which are antibodies that can fight against multiple variants of a virus. The idea behind creating this vaccine is to identify the right types of bnAbs and human genes to create an mRNA vaccine that prevents the infection or spread of HIV.

“Our 2 studies describe a collaborative effort to genetically and structurally understand bnAbs, and ultimately ‘reverse engineer’ vaccines to elicit these bnAbs,” said senior author William Schief, PhD, a Scripps Research professor and executive director of vaccine design at IAVI's Neutralizing Antibody Center at Scripps Research, in a press release.

The research teams from Scripps and IAVI first engineered a priming immunogen for (what would be) the first dose of the HIV vaccine. This manufactured spike protein would bind to specific naïve B cells, also called germline precursors.

Naïve B cells are antibody-producing white blood cells, and bnAbs come from these cells. The team analyzed 1.2 billion antibody sequences in a large database, which revealed 2 bnAbs that contained the most naïve B cells. The team suggested that these 2 bnAbs would thus be the best defense against HIV.

“Finding the bnAbs we need is like searching for a needle in a haystack,” said co-first author Zachary Berndsen, PhD, assistant professor of biochemistry at the University of Missouri, in a press release. “To make an effective vaccine, we must first find the precursor antibodies that can eventually become bnAbs, while also seeing if those precursor antibodies are common enough throughout the general population to stimulate.”

The researchers then collaborated with researchers from Ragon Institute. They tested the engineered HIV spike protein in mice and found that it did elicit a response in germline precursor cells. This results in a naïve B cell that expresses the apex bnAbs, which can defend against the virus.

“This is a very important step, as it shows that vaccinating with our immunogen can actually elicit responses from the precursors we were targeting,” said co-first author Jordan Willis, PhD, senior principal scientist at the IAVI Neutralizing Antibody Center at Scripps Research, in the press release. “We also showed that vaccinating with an unmodified HIV protein could not elicit those responses, which proves that our affinity engineering was required."

The HIV mRNA vaccine, which would come from Moderna, would be similar to the COVID-19 vaccine. The benefits are that mRNA vaccines are easier and faster to manufacture, and provide better antibody responses compared to a normal vaccine. The researchers anticipate that they will eventually test this vaccine in human clinical trials.

“We and our collaborators are building on this approach, developing and testing immunogens to drive the later stages of bnAb maturation,” said Facundo Batista, PhD, associate director of the Ragon Institute, in the press release.

Reference

Scripps Research Institute. Scientists design and validate promising HIV vaccine strategy. EurekAlert. October 3, 2022. Accessed on October 5, 2022. https://www.eurekalert.org/news-releases/966725