Seroepidemiological study reveals low neutralizing immunity against avian influenza A(H5N1) in the US population, suggesting susceptibility to infection despite cross-reactive antibodies.
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 conducted a comprehensive assessment of the population 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. Low pre-existing neutralizing and hemagglutinin (HA) head binding antibodies and substantial cross reactive binding antibodies to N1 neuraminidase (NA) of 2.3.4.4b A(H5N1) were detected in US population. Antibodies to group 1 HA stalk were also prevalent with an age-related pattern. A(H1N1)pdm09 infection and influenza vaccination did not induce neutralizing antibodies but induced significant rise of NA inhibition (NAI) antibodies to N1 of 2.3.4.4b A(H5N1), and group 1 HA stalk antibodies. Understanding population susceptibility to novel influenza is essential for pandemic preparedness.
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Li et al. (2025) studied this question.
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