T-cell Immune Responses After mRNA-1273 Vaccination in Children 6 Months–11 Years
Overview
The mRNA-1273 vaccine induces robust, durable Th1-biased CD4+ T-cell responses in children aged 6 months to 11 years, with responses detectable up to 6 months post-vaccination. CD8+ T-cell responses were less frequent in younger children, especially those under 2 years. These T-cell responses correlated with neutralizing antibody levels across age groups.
Background
COVID-19 can cause severe respiratory illness in children, and vaccination reduces infection risk and severe outcomes. While neutralizing antibodies are important, cell-mediated immunity, particularly T-cell responses, plays a critical role in protection against SARS-CoV-2 variants less susceptible to antibodies. Pediatric data on T-cell responses post-vaccination are limited, with evidence suggesting age-dependent differences in magnitude and durability. The mRNA-1273 vaccine was authorized for children based on safety and humoral immunogenicity data from the KidCOVE trial.
Data Highlights
Age Group
Dose
Participants (mRNA-1273 / Placebo)
CD4+ T-cell Response
CD8+ T-cell Response
Response Duration
6 months to 5 years
25 µg
51 / 17 total (subset)
Robust Th1-biased at days 43 and 209
Less frequent, especially <2 years
Detectable ≥6 months
6 to 11 years
50 µg
Same as above
Robust Th1-biased at days 43 and 209
More frequent than younger children
Detectable ≥6 months
Key Findings
Two doses of mRNA-1273 induced strong SARS-CoV-2 spike-specific CD4+ T-cell responses with a Th1-biased profile in children aged 6 months to 11 years.
CD8+ T-cell responses were less commonly detected in children under 5 years and undetectable in those younger than 2 years.
Polyfunctional CD4+ T cells specific to spike protein were significantly higher post-vaccination compared to placebo at day 43, with responses declining but still present at day 209.
There was a positive correlation between Th1 CD4+ T-cell responses and neutralizing antibody titers across all pediatric age groups.
The vaccine elicited durable T-cell immunity lasting at least 6 months after the primary series.
Clinical Implications
These findings support the use of mRNA-1273 vaccination in young children to induce durable cellular immunity, which may contribute to protection against SARS-CoV-2 variants. The age-dependent variability in CD8+ T-cell responses suggests that younger children may rely more on CD4+ T-cell mediated immunity. Monitoring T-cell responses could inform optimal booster timing in pediatric populations.
Conclusion
The mRNA-1273 primary series elicits robust, durable Th1-biased CD4+ T-cell responses in children aged 6 months to 11 years, with variable CD8+ T-cell responses by age. This cellular immunity likely complements antibody responses to provide sustained protection against COVID-19.
References
KidCOVE Trial Investigators 2023 -- Assessment of T-cell Immune Responses Following mRNA-1273 Vaccination in Pediatric Patients
by Christina A Rostad, James D Campbell, Grant C Paulsen, Sabine Schnyder Ghamloush, Wenqin Xu, Lingyi Zheng, M Juliana McElrath, Stephen C De Rosa, Bethany Girard, Rituparna Das, Evan J Anderson, C Buddy Creech, on behalf of the KidCOVE CMI Study Group
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