tetano
Editor, Senior Moderator
Sci Transl Med
. 2025 Jan 29;17(783):eadq1086.
doi: 10.1126/scitranslmed.adq1086. Epub 2025 Jan 29. Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection
Leslie Chan[SUP] 1 2 [/SUP], Kassandra Pinedo[SUP] 2 [/SUP], Mikayla A Stabile[SUP] 2 [/SUP], Rebecca E Hamlin[SUP] 2 [/SUP], Shaun M Pienkos[SUP] 2 [/SUP], Kalani Ratnasiri[SUP] 1 2 [/SUP]; Stanford COVID-19 Biobank; Samuel Yang[SUP] 3 [/SUP], Andra L Blomkalns[SUP] 3 [/SUP], Kari C Nadeau[SUP] 2 4 [/SUP], Bali Pulendran[SUP] 5 6 7 [/SUP], Ruth O'Hara[SUP] 8 [/SUP], Angela J Rogers[SUP] 2 [/SUP], Susan P Holmes[SUP] 9 [/SUP], Catherine A Blish[SUP] 2 10 11 [/SUP]
Collaborators, Affiliations
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.
. 2025 Jan 29;17(783):eadq1086.
doi: 10.1126/scitranslmed.adq1086. Epub 2025 Jan 29. Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection
Leslie Chan[SUP] 1 2 [/SUP], Kassandra Pinedo[SUP] 2 [/SUP], Mikayla A Stabile[SUP] 2 [/SUP], Rebecca E Hamlin[SUP] 2 [/SUP], Shaun M Pienkos[SUP] 2 [/SUP], Kalani Ratnasiri[SUP] 1 2 [/SUP]; Stanford COVID-19 Biobank; Samuel Yang[SUP] 3 [/SUP], Andra L Blomkalns[SUP] 3 [/SUP], Kari C Nadeau[SUP] 2 4 [/SUP], Bali Pulendran[SUP] 5 6 7 [/SUP], Ruth O'Hara[SUP] 8 [/SUP], Angela J Rogers[SUP] 2 [/SUP], Susan P Holmes[SUP] 9 [/SUP], Catherine A Blish[SUP] 2 10 11 [/SUP]
Collaborators, Affiliations
- PMID: 39879318
- DOI: 10.1126/scitranslmed.adq1086
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.