Researchers have identified a previously unrecognised class of antibodies that appear capable of neutralising multiple forms of influenza virus. These findings, which could contribute to development of more broadly protective vaccines, were published 21 December by Holly Simmons of the University of Pittsburgh School of Medicine, US, and colleagues in the open access journal PLOS Biology.
An influenza vaccine prompts the immune system to make antibodies that can bind to a viral protein called hemagglutinin on the outside of an invading influenza virus, blocking it from entering a person’s cells. Different antibodies bind to different parts of hemagglutinin in different ways, and hemagglutinin itself evolves over time, resulting in the emergence of new influenza strains that can evade old antibodies. New vaccines are offered each year based on predictions of whatever the most dominant strains will be.
Extensive research efforts are paving the way to development of vaccines that are better at protecting against multiple strains at once. Many scientists are focused on antibodies that can simultaneously protect against influenza subtypes known as H1 and H3, which come in multiple strains and are responsible for widespread infection.
Simmons and colleagues homed in on a particular challenge in this endeavour - a small change found in some H1 strains in the sequence of building blocks that makes up hemagglutinin. Certain antibodies capable of neutralising H3 can also neutralise H1, but not if its hemagglutinin has this change, known as the 133a insertion.
Now, in a series of experiments conducted with blood samples from patients, the researchers have identified a novel class of antibodies capable of neutralising both certain H3 strains and certain H1 strains with or without the 133a insertion. Distinct molecular characteristics set these antibodies apart from other antibodies capable of cross-neutralising H1 and H3 strains via other means.
This research expands the list of antibodies that could potentially contribute to development of a influenza virus that achieves broader protection through an assortment of molecular mechanisms. It also adds to growing evidence supporting a move away from influenza vaccines grown in chicken eggs - currently the most common manufacturing approach.
The authors commented: “We need annual influenza virus vaccines to keep pace with continuing viral evolution. Our work suggests that the barriers to eliciting more broadly protective immunity may be surprisingly low. Given the right series of influenza virus exposures/vaccinations, it is possible to for humans to mount robust antibody responses that neutralise divergent H1N1 and H3N2 viruses, opening new avenues to design improved vaccines.”
- Simmons HC, Watanabe A, Oguin III TH, et al. A new class of antibodies that overcomes a steric barrier to cross-group neutralization of influenza viruses. PLoS Biol 21(12): e3002415. https://doi.org/10.1371/journal.pbio.3002415
Illustration shows convergent H1N1-H3N2 neutralising antibody responses to influenza virus. Panels are derived from structures reported by Simmons et al., (PDB 7TRH, 7RRI and 3UBE by Xu et al., for the model of receptor engagement).