biostudies-literatureAhimbisibwe GUniversity College London Hospitals NHS Foundation TrustCancer Research UKMedical Research CouncilNIHR University College London Hospitals Biomedical Research CentreThe Francis Crick InstituteNIHR Imperial Biomedical Research CentreImperial College Healthcare NHS TrustWellcome TrustUK Research and Innovation106598https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618389biostudies-literatureUnknown91(3)<h4>Background</h4>In 2021, the rapid rollout of two doses of SARS-CoV-2 vaccines reduced COVID-19 severity and mortality. However, further vaccine doses as a prime-boost schedule were limited, and lifting of public health restrictions by late 2021 frequently led to infection, rather than vaccine, as a third exposure.<h4>Objective</h4>To compare how the third exposure through mRNA booster or SARS-CoV-2 infection shapes humoral and cellular immunity following two vaccine doses.<h4>Methods</h4>We compared immune responses after the third exposure in healthy adults enrolled in the UCLH-Crick Legacy cohort study (NCT04750356) between those receiving ancestral spike-encoded mRNA booster (vaccine immunity, n = 38) or COVID-19 infection (hybrid immunity, n = 13) following two vaccine doses. ImmunThe Journal of infectionThird exposure to COVID-19 infection or vaccination differentially impacts T cell responses.PMC7618389MR/W005611/1CC2230CC2166CC2060226817CC2041CC1283222574MR/X006751/1CC0102CC1114MR/Y004205/1CC2112Penn RSwanton CCarr EJLevi DAhimbisibwe GGahir JMiah MHarvey RWilkinson RJBawumia PWilliams BBauer DLRiddell ALegacy InvestigatorsKelly GTownsley HDaley OBazire JKjar SStevenson-Leggett PSmith CGamblin SSanderson TFowler ASHobson PWilkinson KADowgier GAmbrose KHobbs AGreenwood DLibri VGandhi SWall ECMiranda MO'Reilly NWarchal SStrange AChaloner CfalseThird exposure to COVID-19 infection or vaccination differentially impacts T cell responses.<h4>Background</h4>In 2021, the rapid rollout of two doses of SARS-CoV-2 vaccines reduced COVID-19 severity and mortality. However, further vaccine doses as a prime-boost schedule were limited, and lifting of public health restrictions by late 2021 frequently led to infection, rather than vaccine, as a third exposure.<h4>Objective</h4>To compare how the third exposure through mRNA booster or SARS-CoV-2 infection shapes humoral and cellular immunity following two vaccine doses.<h4>Methods</h4>We compared immune responses after the third exposure in healthy adults enrolled in the UCLH-Crick Legacy cohort study (NCT04750356) between those receiving ancestral spike-encoded mRNA booster (vaccine immunity, n = 38) or COVID-19 infection (hybrid immunity, n = 13) following two vaccine doses. Immun2025-01-01T00:00:00Z2025 Sep2026-06-05T18:33:12.113Z2026-05-20T03:12:12.828ZS-EPMC76183894084899010.1016/j.jinf.2025.106598