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Evaluation of Cellular Immune Responses After mRNA-1273 Vaccination in Children 6 Months to 11 Years of Age
Christina A Rostad1, James D Campbell2, Grant C Paulsen3
1Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Insights
The mRNA-1273 vaccine generates durable, T-helper 1-biased CD4+ T-cell responses in children aged 6 months to 11 years, contributing to cell-mediated immunity against SARS-CoV-2 variants. CD8+ T-cell responses were age-dependent.
Area of Science:
- Immunology
- Vaccinology
- Pediatric Infectious Diseases
Background:
- Cell-mediated immunity (CMI) is crucial for protection against SARS-CoV-2 variants less susceptible to neutralizing antibodies.
- Evaluating CMI post-vaccination in pediatric populations is essential for understanding vaccine efficacy.
Purpose of the Study:
- To assess cell-mediated immunity (CMI) following the mRNA-1273 primary vaccination series in children aged 6 months to 11 years.
- To characterize T-cell responses, including magnitude, phenotype, and polyfunctionality, in response to SARS-CoV-2 spike protein.
Main Methods:
- Participants (6 months–11 years) received two doses of mRNA-1273 (25 or 50 microg) or placebo, 28 days apart.
- T-cell responses were analyzed using intracellular cytokine staining and polyfunctionality assays.
- Assessed responses to pooled ancestral SARS-CoV-2 spike protein peptides.
Main Results:
- mRNA-1273 induced robust, Th1-biased CD4+ T-cell responses detected at day 43 and day 209.
- S-protein-specific CD8+ T-cell responses were less frequent in younger children (<5 years) and undetectable in infants (<2 years).
- Polyfunctional CD4+ T-cell frequencies increased post-vaccination and remained detectable for at least 6 months.
Conclusions:
- The mRNA-1273 primary series provides robust and durable Th1-biased CD4+ T-cell immunity in children aged 6 months to 11 years.
- Age influences the development of CD8+ T-cell responses following mRNA-1273 vaccination.
- CMI data supports the role of mRNA-1273 in broader immune protection beyond neutralizing antibodies.
Background:
Cell-mediated immunity (CMI) may help protect against emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that are less susceptible to neutralizing antibodies. We present CMI data after the mRNA-1273 primary series in a subset of participants aged 6 months to 11 years from the phase 2/3 KidCOVE trial.
Methods:
T-cell responses were assessed after 2 doses of mRNA-1273 (6 months to 5 years, 25 μg; 6-11 years, 50 μg) or placebo administered 28 days apart. Magnitude, phenotype, and percentage of ancestral SARS-CoV-2 spike (S) protein T-cell responses to pooled peptides were assessed by intracellular cytokine staining and polyfunctionality analyses.
Results:
A total of 68 children aged 6 months to 11 years received either the 2-dose mRNA-1273 primary series or placebo (51 and 17, respectively) at 28-day interval. mRNA-1273 induced S-protein-specific CD4+ T-cell responses exhibiting a type 1 T helper (Th1)-biased profile at day 43 and day 209 compared with placebo. S-protein-specific CD8+ T-cell responses were less frequently detected in children <5 years and undetectable in those <2 years. Compared with placebo, mRNA-1273 induced higher frequencies of S-specific polyfunctional CD4+ T cells at day 43; frequencies declined but remained detectable at day 209. Correlation between Th1 CD4+ responses and neutralizing antibodies was observed across age groups following mRNA-1273 vaccination.
Conclusions:
The 2-dose mRNA-1273 primary series elicited robust and durable (≥ 6 months) Th1-biased CD4+ T-cell responses in children aged 6 months to 11 years. CD8+ T-cell responses varied by age. Clinical Trials Registration. NCT04796896.
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