Peer-reviewed article
Pre-vaccination immune signatures of children with inborn errors of immunity associate with COVID-19 vaccine response.
Paolo Palma, Elena Emili, Chiara Pighi, Nicole Colantoni, Elena Morrocchi et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This study examined why children with inborn errors of immunity (genetic conditions affecting the immune system) respond differently to COVID-19 mRNA vaccines. Researchers compared 21 children before and after vaccination and found that those who produced lower antibody levels had fewer switched memory B cells at baseline. Gene expression analysis showed that children with strong vaccine responses had immune cells with greater expression of genes related to activation and memory, suggesting their immune systems were better prepared to generate antibodies.
Key points
- Low responders to the BNT162b2 vaccine had significantly lower frequencies of switched memory B cells compared to high responders (p = 0.014)
- Baseline transcriptional profiling identified 41 differentially expressed genes between high and low responders
- High responders' activated memory B cells showed greater induction of activation and memory-related genes including NFKB1, CD69, TIGIT, CD40L, and BATF
- Vaccine-induced T cell responses were broadly comparable between groups despite differences in antibody production
- Pre-vaccination molecular immune features may enable more personalized vaccination strategies for individuals with impaired immunity
Limitations
The study was small (21 participants) and focused on children with inborn errors of immunity, so findings may not apply to typically developing children or the general population. The study measured only one vaccine type (BNT162b2) at one timepoint post-vaccination (day 28), so durability and response to other vaccines is unknown.
Abstract
Individuals with inborn errors of immunity often mount suboptimal responses to vaccination, yet the molecular determinants underlying their variable responses to mRNA vaccines remain poorly defined. The present study aimed to identify baseline immune transcriptional signatures predictive of humoral responses to the BNT162b2 (Comirnaty) mRNA vaccine in individuals with inborn errors of immunity. Twenty-one SARS-CoV-2-naïve participants with diverse inborn errors of immunity were stratified as high or low responders to the BNT162b2 vaccine based on anti-SARS-CoV-2 spike IgG titers at day 28 post-vaccination. Although vaccine-induced T cell responses were broadly comparable, low responders had significantly lower frequencies of switched memory B cells (p = .014). Transcriptional profiling revealed 41 differentially expressed genes between groups at baseline. Activated memory B cells and peripheral T follicular helper cells from high responders exhibited greater induction of activation and memory-related genes, including NFKB1, CD69, TIGIT, CD40L, and BATF, indicating greater intrinsic readiness to support coordinated antibody production. These findings demonstrate that distinct pre-vaccination gene expression patterns within specific immune subsets are associated with differential humoral responses to mRNA vaccination in individuals with inborn errors of immunity. More broadly, the study highlights that baseline molecular immune features substantially influence vaccine efficacy and suggests that pre-vaccination transcriptional profiling may enable more personalized vaccination strategies for individuals with impaired immunity.
Findings the Hub has extracted
Each claim below is labelled by its type of design and links back to this report.
- Intervention
- mRNA COVID-19 vaccine (BNT162b2/Comirnaty) administered according to standard schedule
- Population
- 21 SARS-CoV-2-naïve children with diverse inborn errors of immunity
Key finding
Low responders had significantly lower frequencies of switched memory B cells at baseline (p = 0.014)