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Robust immunity to influenza vaccination in haematopoietic stem cell transplant recipients following reconstitution of humoral and adaptive immunity.

Zhang W, Rowntree LC, Muttucumaru R, Damelang T, Aban M, Hurt AC, Auladell M, Esterbauer R, Wines B, Hogarth M, Turner SJ, Wheatley AK, Kent SJ, Patil S, Avery S, Morrissey O, Chung AW, Koutsakos M, Nguyen TH, Cheng AC, Kotsimbos TC, Kedzierska K

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  • Journal Clinical & Translational Immunology

  • Published 27 Jun 2023

  • Volume 12

  • ISSUE 6

  • Pagination e1456

  • DOI 10.1002/cti2.1456

Abstract

Influenza causes significant morbidity and mortality, especially in high-risk populations. Although current vaccination regimens are the best method to combat annual influenza disease, vaccine efficacy can be low in high-risk groups, such as haematopoietic stem cell transplant (HSCT) recipients.

We comprehensively assessed humoral immunity, antibody landscapes, systems serology and influenza-specific B-cell responses, together with their phenotypes and isotypes, to the inactivated influenza vaccine (IIV) in HSCT recipients in comparison to healthy controls.

influenza-specific B cells, determined by HA probes and flow cytometry. Strikingly, 40% of HSCT recipients had markedly higher antibody responses towards A/H3N2 vaccine strain than healthy controls and showed cross-reactivity to antigenically drifted A/H3N2 strains by antibody landscape analysis. These superior humoral responses were associated with a greater time interval after HSCT, while multivariant analyses revealed the importance of pre-existing immune memory. Conversely, in HSCT recipients who did not respond to the first dose, the second IIV dose did not greatly improve their humoral response, although 50% of second-dose patients reached a seroprotective HAI titre for at least one of vaccine strains.

Our study demonstrates efficient, although time-dependent, immune responses to IIV in HSCT recipients, and provides insights into influenza vaccination strategies targeted to immunocompromised high-risk groups.