Vaccine additives can enhance immune flexibility – implications for flu and SARS-CoV-2

A vaccine additive known as an adjuvant can enhance responses to a vaccine containing the exotic avian flu virus H5N1, so that both rookie and veteran elements of the immune response are strengthened, according to results from an Emory Vaccine Center study.

The findings have implications for the effort to develop vaccines against multiple strains of flu, as well as the current push for vaccines against SARS-CoV-2. The Emory study was a test of what happens when the body sees something new – in contrast to seasonal flu vaccination, which often re-activates the same memory B cells the immune system relied upon in past years.

The study provides guidance on how adjuvants might become part of a proposed “universal” flu vaccine, aimed at protecting people against a wider variety of influenza strains. In addition, vaccine designers are considering how to optimize immune responses against SARS-Cov-2, which few had encountered before 2020.

The results are scheduled for publication in Proceedings of the National Academy of Sciences.

“We saw that an adjuvant makes it possible to efficiently engage both memory and naive B cells, expanding the repertoire of the antibody immune response to influenza,” says first author Ali Ellebedy, PhD, who did the study while he was a postdoctoral fellow in Rafi Ahmed’s lab at Emory Vaccine Center.

The H5N1 vaccination study was performed at Emory Vaccine Center’s Hope Clinic. Ellebedy is now an assistant professor of pathology and immunology at Washington University School of Medicine in St. Louis. Collaborators from Stanford University and Icahn School of Medicine at Mount Sinai contributed to the paper.

“For a new pathogen like SARS-CoV-2, nobody has immunity,” Ahmed says. “So the important thing is to have the vaccine bring out good responses from naïve B cells, whose frequency is low.”

“For universal flu, the situation is more complicated. You want to bring out both the cross-reactive memory cells and the naïve strain-specific cells,” adds Ahmed, whose lab is part of a NIH-funded consortium developing flu vaccine candidates. “Looking ahead, adjuvants are going to be an important element of universal flu vaccine research.”

The particular adjuvant studied in the paper is called AS03, whose manufacturer GlaxoSmithKline is making it available for COVID-19 vaccine trials. The AS03 adjuvant could be relevant for extending the efficacy of limited doses of protein or viral subunit-based vaccines, but less so for newer mRNA-based vaccines, Ahmed says.

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