A(H2N2) and A(H3N2) influenza pandemics elicited durable cross-reactive and protective antibodies against avian N2 neuraminidases

Zaolan Liang, Xia Lin, Lihong Sun, Kimberly M. Edwards, Wenjun Song, Hailiang Sun, Yanmin Xie, Fangmei Lin, Shiman Ling, Tingting Liang, Biying Xiao, Jiaqi Wang, Min Li, Chin-Yu Leung, Huachen Zhu, Nisha Bhandari, Raghavan Varadarajan, Min Z. Levine, Malik Peiris, Robert Webster, Vijaykrishna Dhanasekaran, Nancy H. L. Leung, Benjamin J. Cowling, Richard J. Webby, Mariette Ducatez, Mark Zanin () and Sook-San Wong ()
Additional contact information
Zaolan Liang: The University of Hong Kong
Xia Lin: The University of Hong Kong
Lihong Sun: Guangzhou Institute for Respiratory Health and First Affiliated Hospital of Guangzhou Medical University
Kimberly M. Edwards: The University of Hong Kong
Wenjun Song: Guangzhou National Laboratory
Hailiang Sun: South China Agricultural University
Yanmin Xie: The University of Hong Kong
Fangmei Lin: Guangzhou Medical University
Shiman Ling: Guangzhou Medical University
Tingting Liang: Guangzhou Medical University
Biying Xiao: Guangzhou Medical University
Jiaqi Wang: Guangzhou Medical University
Min Li: The University of Hong Kong
Chin-Yu Leung: The University of Hong Kong
Huachen Zhu: The University of Hong Kong
Nisha Bhandari: Indian Institute of Science
Raghavan Varadarajan: Indian Institute of Science
Min Z. Levine: US Center for Disease Control and Prevention
Malik Peiris: The University of Hong Kong
Robert Webster: St. Jude Children’s Research Hospital
Vijaykrishna Dhanasekaran: The University of Hong Kong
Nancy H. L. Leung: The University of Hong Kong
Benjamin J. Cowling: The University of Hong Kong
Richard J. Webby: St. Jude Children’s Research Hospital
Mariette Ducatez: National Veterinary School of Toulouse (ENVT)
Mark Zanin: The University of Hong Kong
Sook-San Wong: The University of Hong Kong

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Human cases of avian influenza virus (AIV) infections are associated with an age-specific disease burden. As the influenza virus N2 neuraminidase (NA) gene was introduced from avian sources during the 1957 pandemic, we investigate the reactivity of N2 antibodies against A(H9N2) AIVs. Serosurvey of healthy individuals reveal the highest rates of AIV N2 antibodies in individuals aged ≥65 years. Exposure to the 1968 pandemic N2, but not recent N2, protected against A(H9N2) AIV challenge in female mice. In some older adults, infection with contemporary A(H3N2) virus could recall cross-reactive AIV NA antibodies, showing discernable human- or avian-NA type reactivity. Individuals born before 1957 have higher anti-AIV N2 titers compared to those born between 1957 and 1968. The anti-AIV N2 antibodies titers correlate with antibody titers to the 1957 N2, suggesting that exposure to the A(H2N2) virus contribute to this reactivity. These findings underscore the critical role of neuraminidase immunity in zoonotic and pandemic influenza risk assessment.

Date: 2024
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DOI: 10.1038/s41467-024-49884-9

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