Early mucosal events promote distinct mucosal and systemic antibody responses to live attenuated influenza vaccine

Ryan S. Thwaites (), Ashley S. S. Uruchurtu, Victor Augusti Negri, Megan E. Cole, Nehmat Singh, Nelisa Poshai, David Jackson, Katja Hoschler, Tina Baker, Ian C. Scott, Xavier Romero Ros, Emma Suzanne Cohen, Maria Zambon, Katrina M. Pollock, Trevor T. Hansel and Peter J. M. Openshaw ()
Additional contact information
Ryan S. Thwaites: Imperial College London
Ashley S. S. Uruchurtu: Imperial College London
Victor Augusti Negri: Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca
Megan E. Cole: Imperial College London
Nehmat Singh: Imperial College London
Nelisa Poshai: Imperial College London
David Jackson: United Kingdom Health Security Agency
Katja Hoschler: United Kingdom Health Security Agency
Tina Baker: Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca
Ian C. Scott: Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca
Xavier Romero Ros: Bioscience Asthma and Skin Immunity, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca
Emma Suzanne Cohen: Bioscience Asthma and Skin Immunity, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca
Maria Zambon: United Kingdom Health Security Agency
Katrina M. Pollock: Imperial College London
Trevor T. Hansel: Imperial College London
Peter J. M. Openshaw: Imperial College London

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

Abstract: Abstract Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing influenza in children, but a correlate of protection for LAIV remains unclear. Studying young adult volunteers, we observe that LAIV induces distinct, compartmentalized, antibody responses in the mucosa and blood. Seeking immunologic correlates of these distinct antibody responses we find associations with mucosal IL-33 release in the first 8 hours post-inoculation and divergent CD8+ and circulating T follicular helper (cTfh) T cell responses 7 days post-inoculation. Mucosal antibodies are induced separately from blood antibodies, are associated with distinct immune responses early post-inoculation, and may provide a correlate of protection for mucosal vaccination. This study was registered as NCT04110366 and reports primary (mucosal antibody) and secondary (blood antibody, and nasal viral load and cytokine) endpoint data.

Date: 2023
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DOI: 10.1038/s41467-023-43842-7

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