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<p>Defining vaccine-induced protection in children with humoral immunodeficiency is essential to guide SARS-CoV-2 vaccination strategies in this high-risk population. We conducted a longitudinal analysis of SARS-CoV-2 immunity at 1, 6 and 12 months after a primary Pfizer-BioNTech mRNA vaccine series in 27 children aged 5-11 years with primary or secondary antibody deficiencies and 48 matched healthy controls. Functional T-cell responses were quantified by IFN-γ and IL-2 ELISpot, and SARS-CoV-2-specific B-cells and T-cells were assessed by spectral cytometry. Systemic and mucosal antibody responses were measured in serum and saliva, and neutralizing activity against ancestral and Omicron BA.5 strains was evaluated through microneutralization. Children with humoral immunodeficiency exhibited impaired systemic antibody responses after two mRNA doses, even after SARS-CoV-2 infection. A third dose improved humoral immunity in children with preserved B-cell compartments but did not rescue neutralizing antibody responses in those with severe B-cell lymphopenia. In contrast, preserved, polyfunctional SARS-CoV-2-specific T-cell responses were observed in children with humoral immunodeficiency, including those with severe B-cell lymphopenia, and were higher in asymptomatic immunocompromised children. These findings reveal a dissociation between humoral failure and preserved cellular immunity in B-cell-deficient children, supporting timely vaccination and integration of T-cell responses into vaccine-response assessment when neutralizing antibodies are absent.</p>

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Preserved SARS-CoV-2 T-cell responses despite impaired humoral immunity in children with profound B-cell lymphopenia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Sabryna Nantel,
  • Samuel Sassine,
  • Benoîte Bourdin,
  • Margot Barbosa Da Torre,
  • Gabrielle Sutton,
  • Henintsoa Rabezanahary,
  • Freda Qi,
  • Lesley A. Ward,
  • Melanie Delgado-Brand,
  • Kelsey Adams,
  • Salma Sheikh-Mohamed,
  • Louise Wang,
  • Sylvie Nicholson,
  • Zineb Laghdir,
  • Karen Colwill,
  • Gary Chao,
  • Laurie Seifried,
  • Ying Liu,
  • James M. Rini,
  • Jennifer Gommerman,
  • Anne-Claude Gingras,
  • Mariana Baz,
  • Kate Zinzser,
  • Caroline Quach,
  • Hélène Decaluwe

摘要

Defining vaccine-induced protection in children with humoral immunodeficiency is essential to guide SARS-CoV-2 vaccination strategies in this high-risk population. We conducted a longitudinal analysis of SARS-CoV-2 immunity at 1, 6 and 12 months after a primary Pfizer-BioNTech mRNA vaccine series in 27 children aged 5-11 years with primary or secondary antibody deficiencies and 48 matched healthy controls. Functional T-cell responses were quantified by IFN-γ and IL-2 ELISpot, and SARS-CoV-2-specific B-cells and T-cells were assessed by spectral cytometry. Systemic and mucosal antibody responses were measured in serum and saliva, and neutralizing activity against ancestral and Omicron BA.5 strains was evaluated through microneutralization. Children with humoral immunodeficiency exhibited impaired systemic antibody responses after two mRNA doses, even after SARS-CoV-2 infection. A third dose improved humoral immunity in children with preserved B-cell compartments but did not rescue neutralizing antibody responses in those with severe B-cell lymphopenia. In contrast, preserved, polyfunctional SARS-CoV-2-specific T-cell responses were observed in children with humoral immunodeficiency, including those with severe B-cell lymphopenia, and were higher in asymptomatic immunocompromised children. These findings reveal a dissociation between humoral failure and preserved cellular immunity in B-cell-deficient children, supporting timely vaccination and integration of T-cell responses into vaccine-response assessment when neutralizing antibodies are absent.