NPJ vaccinesJul 20, 2026

Strong T-cell responses to SARS-CoV-2 despite weak antibody immunity in children with very low B-cell levels

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 21, 2026

Abstract

Children with humoral immunodeficiency showed impaired systemic antibody responses after two doses of the Pfizer-BioNTech mRNA vaccine.

A longitudinal analysis was conducted on 27 children with antibody deficiencies and 48 healthy controls over 12 months.
A third vaccine dose improved humoral immunity in children with some B-cell function but did not restore neutralizing antibodies in those with severe B-cell deficiencies.
Preserved and functional T-cell responses were found in children with humoral immunodeficiency, including those with severe B-cell lymphopenia.
Higher T-cell responses were noted in asymptomatic immunocompromised children.
These results indicate a separation between ineffective antibody production and maintained cellular immune responses in B-cell-deficient children.

Simplified

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.

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PubMed

Strong T-cell responses to SARS-CoV-2 despite weak antibody immunity in children with very low B-cell levels

Abstract

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Competing interests

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