| Title: |
Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection |
| Authors: |
Chan, Leslie; Pinedo, Kassandra; Stabile, Mikayla A.; Hamlin, Rebecca E.; Pienkos, Shaun M.; Ratnasiri, Kalani; Yang, Samuel; Blomkalns, Andra L.; Nadeau, Kari C.; Pulendran, Bali; O’Hara, Ruth; Rogers, Angela J.; Holmes, Susan P.; Blish, Catherine A.; Ranganath, Thanmayi; Zhao, Nancy Q.; Wilk, Aaron J.; Vergara, Rosemary; McKechnie, Julia L.; de la Parte, Lauren; Dantzler, Kathleen Whittle; Ty, Maureen; Kathale, Nimish; Martínez-Colón, Giovanny J.; Rustagi, Arjun; Ivison, Geoff; Pi, Ruoxi; Lee, Madeline J.; Brewer, Rachel E.; Hollis, Taylor; Baird, Andrea; Ugur, Michele; Tal, Michal C.; Bogusch, Drina; Nahass, Georgie; Haider, Kazim; Thi Tran, Kim Quyen; Simpson, Laura; Din, Hena N.; Roque, Jonasel; Mann, Rosen; Chang, Iris; Do, Evan; Fernandes, Andrea; Lyu, Shu-Chen; Zhang, Wenming; Manohar, Monali; Krempski, James W.; Visweswaran, Anita; Zudock, Elizabeth J. |
| Source: |
Science Translational Medicine ; volume 17, issue 783 ; ISSN 1946-6234 1946-6242 |
| Publisher Information: |
American Association for the Advancement of Science (AAAS) |
| Publication Year: |
2025 |
| Description: |
At this stage in the COVID-19 pandemic, most infections are “breakthrough” infections that occur in individuals with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. To refine long-term vaccine strategies against emerging variants, we examined both innate and adaptive immunity in breakthrough infections. We performed single-cell transcriptomic, proteomic, and functional profiling of primary and breakthrough infections to compare immune responses from unvaccinated and vaccinated individuals during the SARS-CoV-2 Delta wave. Breakthrough infections were characterized by a less activated transcriptomic profile in monocytes and natural killer cells, with induction of pathways limiting monocyte migratory potential and natural killer cell proliferation. Furthermore, we observed a female-specific increase in transcriptomic and proteomic activation of multiple innate immune cell subsets during breakthrough infections. These insights suggest that prior SARS-CoV-2 vaccination prevents overactivation of innate immune responses during breakthrough infections with discernible sex-specific patterns and underscore the potential of harnessing vaccines in mitigating pathologic immune responses resulting from overactivation. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1126/scitranslmed.adq1086 |
| Availability: |
https://doi.org/10.1126/scitranslmed.adq1086; https://www.science.org/doi/pdf/10.1126/scitranslmed.adq1086 |
| Accession Number: |
edsbas.6B1AFFC4 |
| Database: |
BASE |