Antibody-mediated NK cell activation as a correlate of immunity against influenza infection

Carolyn M. Boudreau, John S. Burke, Ashraf S. Yousif, Maya Sangesland, Sandra Jastrzebski, Chris Verschoor, George Kuchel, Daniel Lingwood, Harry Kleanthous, Iris Bruijn, Victoria Landolfi, Saranya Sridhar () and Galit Alter ()
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Carolyn M. Boudreau: MIT, and Harvard
John S. Burke: MIT, and Harvard
Ashraf S. Yousif: MIT, and Harvard
Maya Sangesland: MIT, and Harvard
Sandra Jastrzebski: UCONN Health Center
Chris Verschoor: McMaster University
George Kuchel: UCONN Health Center
Daniel Lingwood: MIT, and Harvard
Harry Kleanthous: SK Bioscience
Iris Bruijn: Sanofi-Pasteur, Inc.
Victoria Landolfi: Sanofi-Pasteur, Inc.
Saranya Sridhar: Sanofi-Pasteur, Inc.
Galit Alter: MIT, and Harvard

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Antibodies play a critical role in protection against influenza; yet titers and viral neutralization represent incomplete correlates of immunity. Instead, the ability of antibodies to leverage the antiviral power of the innate immune system has been implicated in protection from and clearance of influenza infection. Here, post-hoc analysis of the humoral immune response to influenza is comprehensively profiled in a cohort of vaccinated older adults (65 + ) monitored for influenza infection during the 2012/2013 season in the United States (NCT: 01427309). While robust humoral immune responses arose against the vaccine and circulating strains, influenza-specific antibody effector profiles differed in individuals that later became infected with influenza, who are deficient in NK cell activating antibodies to both hemagglutinin and neuraminidase, compared to individuals who remained uninfected. Furthermore, NK cell activation was strongly associated with the NK cell senescence marker CD57, arguing for the need for selective induction of influenza-specific afucosylated NK activating antibodies in older adults to achieve protection. High dose vaccination, currently used for older adults, was insufficient to generate this NK cell-activating humoral response. Next generation vaccines able to selectively bolster NK cell activating antibodies may be required to achieve protection in the setting of progressively senescent NK cells.

Date: 2023
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DOI: 10.1038/s41467-023-40699-8

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