627 - Unique patterns of SARS-CoV-2 immunity in vaccinated children

Saturday, April 29, 2023

3:30 PM – 6:00 PM ET

Poster Number: 627
Publication Number: 627.225

Regina K. Rowe, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States; Nelson Huertas, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States; Bailey Matthews, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States; Jennifer L.. Nayak, University of Rochester Medical Center, Rochester, NY, United States

Presenting Author(s)

Jennifer L. Nayak, MD (she/her/hers)

Associate Professor
University of Rochester Medical Center
Rochester, New York, United States

Background: Coronaviruses are endemic in the human population and are responsible for epidemics as well as pandemics, including the recent SARS-CoV-2 pandemic. As a betacoronavirus, SARS-CoV-2 is closely related to the two endemic coronaviruses (OC43 and HKU1). While it has been shown that age and immunologic history impact immune function and development, there are large knowledge gaps in the specific immune mechanisms governing age-related immunity.

Objective:

We sought to identify age-specific differences in the innate and memory T cell immune responses to SARS-CoV-2, as quantitative and qualitative early life differences in immune function may be responsible for age-related variation in disease presentation and vaccine responses.

Design/Methods:

Peripheral blood mononuclear cells were obtained from cohorts of children and adults enrolled both pre-2019 and following the SARS-CoV-2 pandemic. Subjects enrolled post-pandemic had a history of vaccination against the SARS-CoV-2 virus with a variable infection history. Cells were stimulated with peptides representing the unique (S1) and conserved, more cross reactive (S2) portions of the Spike protein for 24 hours, with cytokine release blocked for the last 4 hours of coculture. Subsets of innate cells and SARS-CoV-2-specific CD4 T cells were identified using a 31-plex spectral flow cytometry panel, with immunity to SARS-CoV-2 compared by age and infection history.

Results:

In pre-pandemic samples, adults had a higher frequency of CD4 T cells specific for the more conserved S2 compared to unique S1 epitopes, with more cross-reactive CD4 T cells detectable in adults compared to children. Interestingly, while subjects enrolled pre-2019 demonstrated greater reactivity to conserved compared to unique epitopes, the CD4 T cell response in both adults and children became more balanced following COVID-19 exposure. Overall, CD4 T cells from pediatric subjects had a less polyfunctional cytokine response compared to adults.

Conclusion(s): Baseline cross-reactive CD4 T cell reactivity to conserved epitopes within the SARS-CoV-2 Spike protein was detectable in adults pre-pandemic, with this reactivity boosted in both children and adults following SARS-CoV-2 exposure. CD4 T responses to both unique and conserved Spike protein epitopes were boosted in children and adults post-pandemic, suggesting that exposure to the SARS-CoV-2 virus via vaccination did not preferentially boost memory CD4 T cells specific for conserved epitopes. Future work will further explore the immune response to COVID-19 in children and correlate the innate immune response to CD4 T cell function.