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Robust immunity to influenza vaccination in haematopoietic stem cell transplant recipients following reconstitution of humoral and adaptive immunity.
Zhang, Wuji; Rowntree, Louise C; Muttucumaru, Ramona; Damelang, Timon; Aban, Malet; Hurt, Aeron C; Auladell, Maria; Esterbauer, Robyn; Wines, Bruce; Hogarth, Mark; Turner, Stephen J; Wheatley, Adam K; Kent, Stephen J; Patil, Sushrut; Avery, Sharon; Morrissey, Orla; Chung, Amy W; Koutsakos, Marios; Nguyen, Thi Ho; Cheng, Allen C; Kotsimbos, Tom C; Kedzierska, Katherine.
  • Zhang W; Department of Microbiology and Immunology University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Rowntree LC; Department of Microbiology and Immunology University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Muttucumaru R; Department of Infectious Diseases Alfred Health Melbourne VIC Australia.
  • Damelang T; Department of Microbiology and Immunology University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Aban M; World Health Organisation (WHO) Collaborating Centre for Reference and Research on Influenza, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Hurt AC; World Health Organisation (WHO) Collaborating Centre for Reference and Research on Influenza, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Auladell M; Product Development Medical Affairs, Infectious Diseases F. Hoffmann-La Roche Ltd Basel Switzerland.
  • Esterbauer R; Department of Microbiology and Immunology University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Wines B; Department of Microbiology and Immunology University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Hogarth M; Burnet Institute Melbourne VIC Australia.
  • Turner SJ; Burnet Institute Melbourne VIC Australia.
  • Wheatley AK; Infection and Immunity Program, Monash Biomedicine Discovery Institute, and Department of Microbiology Monash University Clayton VIC Australia.
  • Kent SJ; Department of Microbiology and Immunology University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Patil S; Department of Microbiology and Immunology University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Avery S; Melbourne Sexual Health Centre, Infectious Diseases Department, Alfred Health, Central Clinical School Monash University Melbourne VIC Australia.
  • Morrissey O; Malignant Haematology and Stem Cell Transplantation Service, Department of Clinical Haematology The Alfred Hospital Melbourne VIC Australia.
  • Chung AW; Malignant Haematology and Stem Cell Transplantation Service, Department of Clinical Haematology The Alfred Hospital Melbourne VIC Australia.
  • Koutsakos M; Department of Infectious Diseases Alfred Health Melbourne VIC Australia.
  • Nguyen TH; Department of Microbiology and Immunology University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Cheng AC; Department of Microbiology and Immunology University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Kotsimbos TC; Department of Microbiology and Immunology University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Kedzierska K; School of Public Health and Preventive Medicine Monash University Clayton VIC Australia.
Clin Transl Immunology ; 12(6): e1456, 2023.
Article en En | MEDLINE | ID: mdl-37383182
ABSTRACT

Objectives:

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.

Methods:

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.

Results:

Inactivated influenza vaccine significantly increased haemagglutination inhibition (HAI) titres in HSCT recipients, similar to healthy controls. Systems serology revealed increased IgG1 and IgG3 antibody levels towards the haemagglutinin (HA) head, but not to neuraminidase, nucleoprotein or HA stem. IIV also increased frequencies of total, IgG class-switched and CD21loCD27+ 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.

Conclusions:

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.
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