In a new study, researchers found 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.
The findings have implications for the effort to develop vaccines against multiple strains of flu, as well as the current push for vaccines against COVID-19.
The research was conducted by a team at the Emory Vaccine Center.
The 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 the COVID-19 virus, which few had encountered before 2020.
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.
The study recruited 50 healthy young adults, who were (most likely) exposed to other flu viruses and vaccines earlier in their lives.
The H5N1 vaccine, with AS03, was approved by the FDA in 2013 and is part of the national stockpile in case of pandemic flu.
The researchers had previously observed that when the immune system encounters an unfamiliar flu virus, which occurred for many during the 2009 H1N1 pandemic, the antibodies produced are able to neutralize a broader range of viruses.
This came from the skew of the antibodies toward the “stem” (or stalk) region of the viral hemagglutinin protein, versus the “head.” The stem region doesn’t mutate and change as much as the head from year to year.
A similar phenomenon occurred in the H5N1 study, because the head region of the virus was unfamiliar, but the stem region was not. Without an adjuvant, the immune response to a low dose of the H5N1 flu vaccine was poor.
But with the adjuvant, immune responses changed markedly between the first and second dose. A week after the first adjuvanted vaccine dose, broadly cross-reactive antibodies produced by the immune system were mostly directed against the stem.
The researchers also offered an explanation for the shift in the antibody response after the second dose: essentially, the immune system is getting in its own way.
After the second vaccination, the antibodies against the stem region are still in the body and they appear to be covering up those parts of the viral hemagglutinin protein, a phenomenon called “epitope blocking.”
One author of the study is Ali Ellebedy, Ph.D.
The study is published in the Proceedings of the National Academy of Sciences.
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