Humans develop convergent H1N1-H3N2 neutralizing antibody responses against the influenza virus. The panels are derived from the structures reported by Simmons et al. (PDB 7TRH, 7RRI and 3UBE from Xu et al., for the receptor engagement model). Credit: Kevin McCarthy (CC-BY 4.0, creativecommons.org/licenses/by/4.0/)
Researchers have identified a previously little-known class of antibodies – immune system proteins that protect against illness – that appear capable of neutralizing several forms of influenza viruses. These findings, which could contribute to the development of more broadly protective flu vaccines, were published by Holly Simmons of the University of Pittsburgh School of Medicine and colleagues in the open access journal. Biology PLOS.
A flu vaccine triggers the immune system to produce antibodies that can bind to a viral protein called hemagglutinin on the outside of an invading flu virus, preventing it from entering a person’s cells. Different antibodies bind to different parts of the hemagglutinin in different ways, and the hemagglutinin itself changes over time, leading to the emergence of new flu strains that can evade old antibodies. New flu vaccines are proposed each year based on predictions about the most dominant strains.
Extensive research efforts are paving the way for the development of flu vaccines that better protect against multiple strains at once. Many scientists are focusing on antibodies that can simultaneously protect against flu subtypes called H1 and H3, which come in several strains and are responsible for widespread infection.
Simmons and his colleagues focused on one particular challenge in this endeavor: a small change found in some H1 strains in the sequence of the building blocks that make up hemagglutinin. Some antibodies that can neutralize H3 can also neutralize H1, but not if its hemagglutinin has this modification, known as the 133a insertion.
Now, in a series of experiments conducted with patient blood samples, researchers have identified a new class of antibodies capable of neutralizing both certain H3 strains and certain H1 strains with or without a 133a insertion. Distinct molecular characteristics distinguish these antibodies from other antibodies capable of cross-neutralizing H1 and H3 strains by other means.
This research expands the list of antibodies that could potentially contribute to the development of a flu vaccine that provides broader protection through an assortment of molecular mechanisms. It also adds to growing evidence supporting a move away from flu vaccines grown in chicken eggs, the currently most common manufacturing approach.
The authors add: “We need annual influenza virus vaccines to keep up with continued viral evolution. Our work suggests that the barriers to achieving broader protective immunity may be surprisingly low. Given the correct series of exposures/vaccinations to the influenza virus, it is possible for humans to develop robust antibody responses that neutralize the divergent H1N1 and H3N2 viruses, opening new avenues for designing improved vaccines .
More information:
Simmons HC, Watanabe A, Oguin III TH, Van Itallie ES, Wiehe KJ, Sempowski GD et al. (2023) A novel class of antibodies that overcomes a steric barrier for cross-group neutralization of influenza viruses. PLoS Biology (2023). DOI: 10.1371/journal.pbio.3002415
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