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

Abstract

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.

One year safety and immunogenicity of AZD1222 (ChAdOx1 nCoV-19): Final analysis of a randomized, placebo-controlled phase 1/2 trial in Japan

“…Consistent with the primary analysis, our follow-up used standardized assays against ancestral SARS-CoV-2. Other studies of SARS-CoV-2 variant specific neutralizing antibody responses post-AZD1222 indicate responses against the Omicron variant are low following two-dose primary vaccination but increase after additional AZD1222 doses [14] , [15] .…”

Evaluation of SARS-CoV-2 anti-Spike antibody levels and breakthrough infection risk among vaccinated adults in North Lebanon

“…This observation may provide additional insights into the potential association between breakthrough infections and the Delta and Omicron variants. Indeed, although some data revealed that 2 doses of the BNT162b2 or AstraZeneca vaccines have the same effectiveness against SARS-CoV-2 Alpha and Delta variants [ 33 ], other studies reported that individuals vaccinated with BNT162b2 are more protected than those vaccinated with AstraZeneca. In this context, an observational study, conducted in the United Kingdom, examined the effectiveness of 2-dose vaccines of either BNT162b2 or AstraZeneca, against infection with Alpha or Delta variants of SARS-CoV-2.…”

Protection against COVID-19 hospitalisation conferred by primary-series vaccination with AZD1222 in non-boosted individuals: first vaccine effectiveness results of the European COVIDRIVE study and meta-regression analysis

“…Our findings on the effectiveness of AZD1222 against hospitalisation are supported by clinical trial data demonstrating the durability of humoral and cellular immunity conferred by primary-series AZD1222 vaccination. 7 , 27 Sustained T-cell responses across SARS-CoV-2 variants have been shown to be important in conferring durable protection against severe disease. 28 …”