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Nat Commun . Pre-existing cross-reactive immunity to highly pathogenic avian influenza 2.3.4.4b A(H5N1) virus in the United States

tetano

Editor, Senior Moderator
Nat Commun


. 2025 Dec 8;16(1):10954.
doi: 10.1038/s41467-025-66431-2. Pre-existing cross-reactive immunity to highly pathogenic avian influenza 2.3.4.4b A(H5N1) virus in the United States

Zhu-Nan Li[SUP] 1 [/SUP], Feng Liu[SUP] 1 [/SUP], Yu-Jin Jung[SUP] 1 [/SUP], Stacie Jefferson[SUP] 1 [/SUP], Crystal Holiday[SUP] 1 [/SUP], F Liaini Gross[SUP] 1 [/SUP], Wen-Pin Tzeng[SUP] 1 [/SUP], Paul Carney[SUP] 1 [/SUP], Ashley Kates[SUP] 2 [/SUP], Ian A York[SUP] 1 [/SUP], Nasia Safdar[SUP] 2 [/SUP], James Zhou[SUP] 3 [/SUP], Marie-Jo Medina[SUP] 3 [/SUP], Vittoria Cioce[SUP] 3 [/SUP], Christine M Oshansky[SUP] 3 [/SUP], C Todd Davis[SUP] 1 [/SUP], James Stevens[SUP] 1 [/SUP], Terrence Tumpey[SUP] 1 [/SUP], Min Z Levine[SUP] 4 [/SUP]



Affiliations
Free article Abstract

The unprecedented 2.3.4.4b. A(H5N1) outbreak in dairy cattle, poultry, and spillover to humans in the United States (US) poses a major public health threat. Population immunity is a critical component of influenza pandemic risk assessment. We assessed the pre-existing cross-reactive immunity to 2.3.4.4b A(H5N1) viruses and analyzed 1794 sera from 723 people (0.5-88 yrs) in multiple US geographic regions during 2021-2024. Pre-existing neutralizing and hemagglutinin (HA)-head-binding antibodies to A(H5N1) were low, but there were substantial cross-reactive binding antibodies to N1 neuraminidase (NA) of 2.3.4.4b A(H5N1). Antibodies to group 1 HA stalk were also prevalent and increased with age. A(H1N1)pdm09 infection and influenza vaccination did not induce neutralizing antibodies to A(H5N1) viruses but induced significant rise of functional NA inhibition (NAI) antibodies to N1 of 2.3.4.4b A(H5N1), and group 1 HA stalk antibodies. Moreover, pre-pandemic stockpiled 2.3.4.4c vaccine can elicit cross-reactive neutralizing antibodies to 2.3.4.4b A(H5N1) viruses. Understanding population susceptibility is essential for pandemic preparedness.


 
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