tetano
Editor, Senior Moderator
Clin Transl Immunology
. 2023 Jun 27;12(6):e1456.
doi: 10.1002/cti2.1456. eCollection 2023. Robust immunity to influenza vaccination in haematopoietic stem cell transplant recipients following reconstitution of humoral and adaptive immunity
Wuji Zhang[SUP] 1 [/SUP], Louise C Rowntree[SUP] 1 [/SUP], Ramona Muttucumaru[SUP] 2 [/SUP], Timon Damelang[SUP] 1 [/SUP], Malet Aban[SUP] 3 [/SUP], Aeron C Hurt[SUP] 3 4 [/SUP], Maria Auladell[SUP] 1 [/SUP], Robyn Esterbauer[SUP] 1 [/SUP], Bruce Wines[SUP] 5 [/SUP], Mark Hogarth[SUP] 5 [/SUP], Stephen J Turner[SUP] 6 [/SUP], Adam K Wheatley[SUP] 1 [/SUP], Stephen J Kent[SUP] 1 7 [/SUP], Sushrut Patil[SUP] 8 [/SUP], Sharon Avery[SUP] 8 [/SUP], Orla Morrissey[SUP] 2 [/SUP], Amy W Chung[SUP] 1 [/SUP], Marios Koutsakos[SUP] 1 [/SUP], Thi Ho Nguyen[SUP] 1 [/SUP], Allen C Cheng[SUP] 9 10 [/SUP], Tom C Kotsimbos[SUP] 11 12 [/SUP], Katherine Kedzierska[SUP] 1 13 [/SUP]
Affiliations
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 CD21[SUP]lo[/SUP]CD27[SUP]+[/SUP] 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.
Keywords: B cells; antibodies; antibody landscapes; haematopoietic stem cell transplant recipients; influenza vaccination; system serology.
. 2023 Jun 27;12(6):e1456.
doi: 10.1002/cti2.1456. eCollection 2023. Robust immunity to influenza vaccination in haematopoietic stem cell transplant recipients following reconstitution of humoral and adaptive immunity
Wuji Zhang[SUP] 1 [/SUP], Louise C Rowntree[SUP] 1 [/SUP], Ramona Muttucumaru[SUP] 2 [/SUP], Timon Damelang[SUP] 1 [/SUP], Malet Aban[SUP] 3 [/SUP], Aeron C Hurt[SUP] 3 4 [/SUP], Maria Auladell[SUP] 1 [/SUP], Robyn Esterbauer[SUP] 1 [/SUP], Bruce Wines[SUP] 5 [/SUP], Mark Hogarth[SUP] 5 [/SUP], Stephen J Turner[SUP] 6 [/SUP], Adam K Wheatley[SUP] 1 [/SUP], Stephen J Kent[SUP] 1 7 [/SUP], Sushrut Patil[SUP] 8 [/SUP], Sharon Avery[SUP] 8 [/SUP], Orla Morrissey[SUP] 2 [/SUP], Amy W Chung[SUP] 1 [/SUP], Marios Koutsakos[SUP] 1 [/SUP], Thi Ho Nguyen[SUP] 1 [/SUP], Allen C Cheng[SUP] 9 10 [/SUP], Tom C Kotsimbos[SUP] 11 12 [/SUP], Katherine Kedzierska[SUP] 1 13 [/SUP]
Affiliations
- PMID: 37383182
- PMCID: PMC10294294
- DOI: 10.1002/cti2.1456
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 CD21[SUP]lo[/SUP]CD27[SUP]+[/SUP] 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.
Keywords: B cells; antibodies; antibody landscapes; haematopoietic stem cell transplant recipients; influenza vaccination; system serology.