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Front Immunol . Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated

tetano

Editor, Senior Moderator
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[SUP] 1 [/SUP], Stephanie Sproule[SUP] 2 [/SUP], Ann R Falsey[SUP] 3 4 [/SUP], Magdalena E Sobieszczyk[SUP] 5 [/SUP], Anne F Luetkemeyer[SUP] 6 [/SUP], Grant C Paulsen[SUP] 7 8 [/SUP], Sharon A Riddler[SUP] 9 [/SUP], Merlin L Robb[SUP] 10 [/SUP], Charlotte-Paige Rolle[SUP] 11 [/SUP], Beverly E Sha[SUP] 12 [/SUP], Tina Tong[SUP] 13 [/SUP], Bahar Ahani[SUP] 14 [/SUP], Anastasia A Aksyuk[SUP] 15 [/SUP], Himanshu Bansal[SUP] 2 [/SUP], Timothy Egan[SUP] 2 [/SUP], Brett Jepson[SUP] 2 [/SUP], Marcelino Padilla[SUP] 15 [/SUP], Nirmeshkumar Patel[SUP] 2 [/SUP], Kathryn Shoemaker[SUP] 2 [/SUP], Ann Marie Stanley[SUP] 15 [/SUP], Phillip A Swanson[SUP] 15 [/SUP], Deidre Wilkins[SUP] 15 [/SUP], Tonya Villafana[SUP] 1 [/SUP], Justin A Green[SUP] 16 [/SUP], Elizabeth J Kelly[SUP] 15 [/SUP]



Affiliations

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.
 
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