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Detailed delineation of the immune response to COVID-19 mRNA vaccination via high-temporal frequency blood transcriptomics [third]

ABSTRACT: mRNA vaccines have played a crucial role in combating the COVID-19 pandemic, but the long-term dynamics of immune responses to repeated vaccination remain poorly understood. In this study, we extend our previous work on first and second dose responses by characterizing the immune signatures elicited by a third dose of COVID-19 mRNA vaccines. Using high-resolution temporal profiling of blood transcriptomes, we analyzed samples collected daily for 9 days post-vaccination across all three doses. We observed distinct patterns of gene expression related to interferon responses, inflammation, erythroid cell signatures, and plasmablast activity. While the first dose elicited a modest response primarily characterized by interferon signaling, the second dose induced a robust, polyfunctional response. Surprisingly, the third dose, administered months later, showed a response pattern that shared similarities with both previous doses but also exhibited unique features. The interferon response following the third dose mirrored the timing of the first dose, peaking on day 2, but matched the amplitude of the second dose. Notably, we observed a progressive amplification of the plasmablast response across the three doses, with an earlier peak (day 4) compared to other vaccines, potentially a unique feature of mRNA vaccines. These findings provide crucial insights into how the immune system adapts to repeated mRNA vaccination over extended periods. They demonstrate that the heightened responsiveness induced by initial doses is maintained months later, suggesting effective immune memory. Our results contribute to a more comprehensive understanding of mRNA vaccine-induced immunity, with implications for optimizing booster strategies and developing next-generation vaccines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281864 | GEO | 2025/01/14

REPOSITORIES: GEO

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Project description:The COVID-19 pandemic has prompted vaccine development efforts on an unprecedented scale. Vaccines based on mRNA technology have emerged as particularly attractive due to their high efficacy and short development timelines. However, relatively little is known about the factors contributing to the development of protective immunity by this new class of vaccines. We employed a high-temporal-resolution transcriptome profiling approach to investigate responses to COVID-19 mRNA vaccination. A cohort of 23 subjects was recruited and changes in blood transcript abundance were measured daily for 9 days post-priming and post-booster vaccination via RNA sequencing. Antibody responses were measured on days 7 and 14 post-vaccination using a custom multiplex assay. Marked differences were observed between responses to the priming and booster doses, with the latter inducing widespread changes in blood transcript abundance consistent with those found in patients with acute viral respiratory infections. The delineation of interferon responses at a high-temporal frequency also suggested that the priming and booster doses elicited distinct types of responses that peaked on day 2 post-priming dose and day 1 post-booster dose. The booster dose also induced inflammation on day 1 and erythroid cell signatures as well as an atypical plasmablast signature on day 4. Notably, this plasmablast signature, together with the post-booster interferon response signature, correlated with the antibody response levels induced on day 14 after the booster dose. Taken together, this work provides a detailed map of the antibody and transcriptional responses to the first and second doses of a new class of vaccine and yields important insights into the mechanisms underlying their immunogenicity. Furthermore, our results suggest that implementing high-temporal-frequency immune profiling protocols may provide an opportunity to better resolve the immune responses elicited by the growing number of available COVID-19 vaccines.

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Detailed delineation of the immune response to COVID-19 mRNA vaccination via high-temporal frequency blood transcriptomics [third]

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