Document Type

Article

Publication Date

4-23-2024

Identifier

DOI: 10.1182/bloodadvances.2023012118; PMCID: PMC11007439

Abstract

Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and prevaccination to postvaccination geometric mean fold rises in antigen-specific (A/H3N2, A/H1N1, and B/Victoria) serum hemagglutination inhibition antibody titers (28-42 days, and ∼6 months after 2 doses). For cell subpopulations identified as predictive of a response to all 3 antigens, we conducted a sensitivity analysis including time after transplant as an additional covariate. Among 156 HCT recipients, we identified 33 distinct immune cell subpopulations; 7 significantly predicted responses to all 3 antigens 28 to 42 days after a 2-dose vaccine series, irrespective of vaccine dose. We also found evidence that baseline absolute numbers of naïve B cells, naïve CD4+ T cells, and circulating T follicular helper cells predicted peak and sustained vaccine-induced titers irrespective of dose or timing of posttransplant vaccine administration. In conclusion, several B- and T-cell subpopulations predicted influenza vaccine immunogenicity in pediatric HCT recipients. This study provides insights into the immune determinants of vaccine responses and may help guide the development of tailored vaccination strategies for this vulnerable population.

Journal Title

Blood Adv

Volume

8

Issue

8

First Page

1880

Last Page

1892

MeSH Keywords

Humans; Child; Influenza, Human; Influenza Vaccines; Transplant Recipients; Hematopoietic Stem Cell Transplantation; Immunogenicity, Vaccine; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Leukocytes, Mononuclear

Keywords

Human Influenza; Influenza Vaccines; Transplant Recipients; Hematopoietic Stem Cell Transplantation; Vaccine Immunogenicity; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Mononuclear Leukocytes

Comments

This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.

Publisher's Link: https://ashpublications.org/bloodadvances/article/8/8/1880/515034/Immunophenotypic-predictors-of-influenza-vaccine

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