Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients.

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 (PBMCs) collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over three influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and pre- to post-vaccination geometric mean fold-rises in antigen-specific (A/H3N2, A/H1N1, and B/Victoria) serum hemagglutination-inhibition antibody titers (28-42 days and approximately 6 months after two doses). For cell subpopulations identified as predictive of a response to all three antigens, we conducted a sensitivity analysis including time post-transplant as an additional covariate. Among 156 HCT recipients, we identified 33 distinct immune cell subpopulations. Seven significantly predicted responses to all three antigens 28-42 days after a two-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 post-transplant 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.