tetano
Editor, Senior Moderator
Cell Rep Med
. 2023 Mar 8;100975.
doi: 10.1016/j.xcrm.2023.100975. Online ahead of print.
Pre-existing Fc profiles shape the evolution of neutralizing antibody breadth following influenza vaccination
Carolyn M Boudreau[SUP] 1 [/SUP], John S Burke 4th[SUP] 2 [/SUP], Alexander L Roederer[SUP] 1 [/SUP], Matthew J Gorman[SUP] 2 [/SUP], Sophia Mundle[SUP] 3 [/SUP], Daniel Lingwood[SUP] 2 [/SUP], Simon Delagrave[SUP] 4 [/SUP], Saranya Sridhar[SUP] 3 [/SUP], Ted M Ross[SUP] 5 [/SUP], Harry Kleanthous[SUP] 6 [/SUP], Galit Alter[SUP] 7 [/SUP]
Affiliations
Abstract
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.
Keywords: FCGR2B; Fc receptor; antibody; hemagglutination inhibition; influenza; vaccine.
. 2023 Mar 8;100975.
doi: 10.1016/j.xcrm.2023.100975. Online ahead of print.
Pre-existing Fc profiles shape the evolution of neutralizing antibody breadth following influenza vaccination
Carolyn M Boudreau[SUP] 1 [/SUP], John S Burke 4th[SUP] 2 [/SUP], Alexander L Roederer[SUP] 1 [/SUP], Matthew J Gorman[SUP] 2 [/SUP], Sophia Mundle[SUP] 3 [/SUP], Daniel Lingwood[SUP] 2 [/SUP], Simon Delagrave[SUP] 4 [/SUP], Saranya Sridhar[SUP] 3 [/SUP], Ted M Ross[SUP] 5 [/SUP], Harry Kleanthous[SUP] 6 [/SUP], Galit Alter[SUP] 7 [/SUP]
Affiliations
- PMID: 36921600
- DOI: 10.1016/j.xcrm.2023.100975
Abstract
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.
Keywords: FCGR2B; Fc receptor; antibody; hemagglutination inhibition; influenza; vaccine.