Pre-existing Fc profiles shape the evolution of neutralizing antibody breadth following influenza vaccination

Under the ever-present threat of a pandemic influenza strain, the evolution of a broadly reactive, neutralizing, functional, humoral immune response may hold the key to protection against both circulating and emerging influenza strains. We apply a systems approach to profile hemagglutinin- and neura...

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Published in:Cell reports. Medicine 2023-03, Vol.4 (3), p.100975-100975, Article 100975
Main Authors: Boudreau, Carolyn M., Burke, John S., Roederer, Alexander L., Gorman, Matthew J., Mundle, Sophia, Lingwood, Daniel, Delagrave, Simon, Sridhar, Saranya, Ross, Ted M., Kleanthous, Harry, Alter, Galit
Format: Article
Language:English
Subjects:
Animals
Antibodies, Neutralizing
Antibodies, Viral
antibody
Fc receptor
FCGR2B
hemagglutination inhibition
Hemagglutinin Glycoproteins, Influenza Virus
Humans
influenza
Influenza Vaccines
Influenza, Human - prevention & control
Mice
Vaccination
vaccine
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Summary:Under the ever-present threat of a pandemic influenza strain, the evolution of a broadly reactive, neutralizing, functional, humoral immune response may hold the key to protection against both circulating and emerging influenza strains. We apply a systems approach to profile hemagglutinin- and neuraminidase-specific humoral signatures that track with the evolution of broad immunity in a cohort of vaccinated individuals and validate these findings in a second longitudinal cohort. Multivariate analysis reveals the presence of a unique pre-existing Fcγ-receptor-binding antibody profile in individuals that evolved broadly reactive hemagglutination inhibition activity (HAI), marked by the presence of elevated levels of pre-existing FCGR2B-binding antibodies. Moreover, vaccination with FCGR2B-binding antibody-opsonized influenza results in enhanced antibody titers and HAI activity in a murine model. Together, these data suggest that pre-existing FCGR2B binding antibodies are a key correlate of the evolution of broadly protective influenza-specific antibodies, providing insight for the design of next-generation influenza vaccines. [Display omitted] •FcγR2-binding antibodies develop with neutralizing antibodies after flu vaccination•FcγR2B binding prior to vaccination leads to broad neutralizing influenza immunity•FcγR2B phenotype is observed across two orthogonal patient cohorts•Pre-existing FcγR2B-binding antibodies increase neutralizing antibody titers in mice Boudreau et al. study the response to influenza vaccination in humans and find that pre-existing antibodies capable of binding to inhibitory Fc γ receptor 2B enhance cross-strain neutralizing immunity after vaccination. This shaping of post-vaccine immunity is mirrored in a mouse model using influenza-specific antibody variants with enhanced binding to Fc receptors.
ISSN:2666-3791
2666-3791
DOI:10.1016/j.xcrm.2023.100975