TY - JOUR AU - Maaske, Jill AU - Sproule, Stephanie AU - Falsey, Ann R. AU - Sobieszczyk, Magdalena E. AU - Luetkemeyer, Anne F. AU - Paulsen, Grant C. AU - Riddler, Sharon A. AU - Robb, Merlin L. AU - Rolle, Charlotte-Paige AU - Sha, Beverly E. AU - Tong, Tina AU - Ahani, Bahar AU - Aksyuk, Anastasia A. AU - Bansal, Himanshu AU - Egan, Timothy AU - Jepson, Brett AU - Padilla, Marcelino AU - Patel, Nirmeshkumar AU - Shoemaker, Kathryn AU - Stanley, Ann Marie AU - Swanson, Phillip A. AU - Wilkins, Deidre AU - Villafana, Tonya AU - Green, Justin A. AU - Kelly, Elizabeth J. PY - 2023 M3 - Original Research TI - Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated JO - Frontiers in Immunology UR - https://www.frontiersin.org/articles/10.3389/fimmu.2022.1062067 VL - 13 SN - 1664-3224 N2 - BackgroundBreakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in coronavirus disease 2019 (COVID-19) vaccinees typically produces milder disease than infection in unvaccinated individuals.MethodsTo explore disease attenuation, we examined COVID-19 symptom burden and immuno-virologic responses to symptomatic SARS-CoV-2 infection in participants (AZD1222: n=177/17,617; placebo: n=203/8,528) from a 2:1 randomized, placebo-controlled, phase 3 study of two-dose primary series AZD1222 (ChAdOx1 nCoV-19) vaccination (NCT04516746).ResultsWe observed that AZD1222 vaccinees had an overall lower incidence and shorter duration of COVID-19 symptoms compared with placebo recipients, as well as lower SARS-CoV-2 viral loads and a shorter median duration of viral shedding in saliva. Vaccinees demonstrated a robust antibody recall response versus placebo recipients with low-to-moderate inverse correlations with virologic endpoints. Vaccinees also demonstrated an enriched polyfunctional spike-specific Th-1-biased CD4+ and CD8+ T-cell response that was associated with strong inverse correlations with virologic endpoints.ConclusionRobust immune responses following AZD1222 vaccination attenuate COVID-19 disease severity and restrict SARS-CoV-2 transmission potential by reducing viral loads and the duration of viral shedding in saliva. Collectively, these analyses underscore the essential role of vaccination in mitigating the COVID-19 pandemic. ER -