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Front Immunol
. 2023 Jan 13;13:1062067.
doi: 10.3389/fimmu.2022.1062067. eCollection 2022.
Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated
Jill Maaske 1 , Stephanie Sproule 2 , Ann R Falsey 3 4 , Magdalena E Sobieszczyk 5 , Anne F Luetkemeyer 6 , Grant C Paulsen 7 8 , Sharon A Riddler 9 , Merlin L Robb 10 , Charlotte-Paige Rolle 11 , Beverly E Sha 12 , Tina Tong 13 , Bahar Ahani 14 , Anastasia A Aksyuk 15 , Himanshu Bansal 2 , Timothy Egan 2 , Brett Jepson 2 , Marcelino Padilla 15 , Nirmeshkumar Patel 2 , Kathryn Shoemaker 2 , Ann Marie Stanley 15 , Phillip A Swanson 15 , Deidre Wilkins 15 , Tonya Villafana 1 , Justin A Green 16 , Elizabeth J Kelly 15
Affiliations
- PMID: 36713413
- PMCID: PMC9881590
- DOI: 10.3389/fimmu.2022.1062067
Abstract
Background: Breakthrough 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.
Methods: To 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).
Results: We 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.
Conclusion: Robust 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.
Keywords: AZD1222 (ChAdOx1 nCoV-19); COVID-19 vaccine; SARS-CoV-2; breakthrough infection; cell-mediated immunity; serology.