A new class of antibodies that overcomes a steric barrier to cross-group neutralization of influenza viruses, 2023, Simmons et al.

[Sly Saint]

Researchers have identified a previously unrecognized class of antibodies-;immune system proteins that protect against disease-;that appear capable of neutralizing multiple forms of flu virus. These findings, which could contribute to development of more broadly protective flu vaccines, will publish December 21st by Holly Simmons of the University of Pittsburgh School of Medicine, US, and colleagues in the open access journal PLOS Biology.

A flu vaccine prompts the immune system to make antibodies that can bind to a viral protein called hemagglutinin on the outside of an invading flu 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 flu strains that can evade old antibodies. New flu 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 flu vaccines that are better at protecting against multiple strains at once. Many scientists are focused on antibodies that can simultaneously protect against flu 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 endeavor-;a small change found in some H1 strains in the sequence of building blocks that makes up hemagglutinin. Certain antibodies capable of neutralizing H3 can also neutralize H1, but not if its hemagglutinin has this change, known as the 133a insertion.

Previously unrecognized class of antibodies can broadly neutralize multiple virus strains (msn.com)

 

[Sean]

Wait, what? You mean there are still important things to learn about how the body works?

I'm shocked, I tell you. Shocked

 

[SNT Gatchaman]

Published as —

A new class of antibodies that overcomes a steric barrier to cross-group neutralization of influenza viruses
Holly C. Simmons; Akiko Watanabe; Thomas H. Oguin III; Elizabeth S. Van Itallie; Kevin J. Wiehe; Gregory D. Sempowski; Masayuki Kuraoka; Garnett Kelsoe; Kevin R. McCarthy

Antibody titers that inhibit the influenza virus hemagglutinin (HA) from engaging its receptor are the accepted correlate of protection from infection. Many potent antibodies with broad, intra-subtype specificity bind HA at the receptor binding site (RBS). One barrier to broad H1-H3 cross-subtype neutralization is an insertion (133a) between positions 133 and 134 on the rim of the H1 HA RBS.

We describe here a class of antibodies that overcomes this barrier. These genetically unrestricted antibodies are abundant in the human B cell memory compartment. Analysis of the affinities of selected members of this class for historical H1 and H3 isolates suggest that they were elicited by H3 exposure and broadened or diverted by later exposure(s) to H1 HA. RBS mutations in egg-adapted vaccine strains cause the new H1 specificity of these antibodies to depend on the egg adaptation.

The results suggest that suitable immunogens might elicit 133a-independent, H1-H3 cross neutralization by RBS-directed antibodies.

Link | PDF (PLOS Biology)