VaccineJul 30, 2026

Strong early immune reactions reduce T cell response to mRNA COVID-19 vaccines

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 3, 2026

Abstract

In a study of 37 immunological naive children aged 6-10, T cell responses three months after SARS-CoV-2 mRNA vaccination were assessed.

Children who had greater T cell responses were categorized as high responders (n=21) compared to low responders (n=15).
Gene expression analysis at day 1 post-vaccination indicated more robust activation of innate immune responses in low responders.
Specific transcription factors, including STAT1, ATF3, and IRF7, showed higher expression in low responders.
In contrast, the expression of LEP, PLCE1, and PLPP2 was significantly reduced in low responders.
The gene expressions in low responders demonstrated strong predictive value for T cell responses at three months post-vaccination, with an area under the receiver operating characteristic curve (AUROC) of 0.89.

Simplified

SARS-CoV-2 mRNA vaccines elicit robust T cell responses in children, resulting in substantial protection against hospitalisation and severe disease. However, the underlying molecular mechanisms that drive this robust cellular immunogenicity of mRNA vaccines in children remains unknown. Here, 37 immunological naïve children underwent primary vaccination (age 6-10) with the SARS-CoV-2 mRNA vaccine and did not acquire natural infection before month 3; bulk RNA sequencing was performed at pre-vaccination baseline and day 1 post vaccination, and Spike-reactive T cell responses were measured at 3 months. Using previously established threshold of T cell responses for clinical protection against symptomatic SARS-CoV-2, we divided our cohort into high responders (n = 21) and low responders (n = 15). Analyses of day 1 post-vaccination gene expression signatures revealed greater induction of innate immune responses, including heightened expression of transcription factors such as STAT1, ATF3 and IRF7 was observed in low responders compared to high responders. On the other hand, LEP, PLCE1 and PLPP2 expression was significantly downregulated in low responders, with strong predictive value for T cell responses at 3 months post-vaccination (AUROC 0.89, 95% CI 0.78-1.00). Taken together, these findings suggest that future mRNA vaccine design and vaccination regimens should aim to modulate excessive innate immune responses to improve T cell responses to mRNA vaccines.

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Funding

Competing interests

No financial or personal ties reported.

PubMed

Strong early immune reactions reduce T cell response to mRNA COVID-19 vaccines

Abstract

Full Text

Funding

Competing interests

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