Durability of protection and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) COVID-19 vaccine over 6 months
Magdalena E. Sobieszczyk, … , and Ian Hirsch, on behalf of the AstraZeneca AZD1222 Clinical Study Group
Magdalena E. Sobieszczyk, … , and Ian Hirsch, on behalf of the AstraZeneca AZD1222 Clinical Study Group
Published September 15, 2022
Citation Information: J Clin Invest. 2022;132(18):e160565. https://doi.org/10.1172/JCI160565.
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Clinical Research and Public Health

Durability of protection and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) COVID-19 vaccine over 6 months

Abstract

Background We report updated safety, efficacy, and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) from an ongoing phase 3 trial.Methods Adults at increased risk of SARS-CoV-2 infection were randomized (2:1), stratified by age, to receive 2 doses of AZD1222 or placebo. The primary efficacy end point was confirmed SARS-CoV-2 reverse-transcriptase PCR–positive (RT-PCR–positive) symptomatic COVID-19 at 15 or more days after a second dose in baseline SARS-CoV-2–seronegative participants. The 21,634 and 10,816 participants were randomized to AZD1222 and placebo, respectively.Findings Data cutoff for this analysis was July 30, 2021; median follow-up from second dose was 78 and 71 days for the double-blind period (censoring at unblinding or nonstudy COVID-19 vaccination) and 201 and 82 days for the period to nonstudy COVID-19 vaccination (regardless of unblinding) in the AZD1222 and placebo groups, respectively. For the primary efficacy end point in the double-blind period (141 and 184 events; incidence rates: 39.2 and 118.8 per 1,000 person years), vaccine efficacy was 67.0% (P < 0.001). In the period to nonstudy COVID-19 vaccination, incidence of events remained consistently low and stable through 6 months in the AZD1222 group; for the primary efficacy end point (328 and 219 events; incidence rates: 36.4, 108.4) and severe/critical disease (5 and 13 events; incidence rates: 0.6, 6.4), respective vaccine efficacy estimates were 65.1% and 92.1%. AZD1222 elicited humoral immune responses over time, with waning at day 180. No emergent safety issues were seen.Conclusion AZD1222 is safe and well tolerated, demonstrating durable protection and immunogenicity with median follow-up (AZD1222 group) of 6 months.Trial registration ClinicalTrials.gov NCT04516746.Funding AstraZeneca; US government.

Authors

Magdalena E. Sobieszczyk, Jill Maaske, Ann R. Falsey, Stephanie Sproule, Merlin L. Robb, Robert W. Frenck Jr., Hong-Van Tieu, Kenneth H. Mayer, Lawrence Corey, Kathleen M. Neuzil, Tina Tong, Margaret Brewinski Isaacs, Holly Janes, Himanshu Bansal, Lindsay M. Edwards, Justin A. Green, Elizabeth J. Kelly, Kathryn Shoemaker, Therese Takas, Tom White, Prakash Bhuyan, Tonya Villafana, and Ian Hirsch, on behalf of the AstraZeneca AZD1222 Clinical Study Group

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Figure 3

Estimated efficacy of AZD1222 versus placebo for the prevention of COVID-19 and SARS-CoV-2 infection during the period to nonstudy COVID-19 vaccination.

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Estimated efficacy of AZD1222 versus placebo for the prevention of COVID...
(A) Cumulative incidence of SARS-CoV-2 RT-PCR–positive symptomatic illness occurring 15 or more days after the second dose (time 0 = day 15 after the second dose) in the FVAS population for the period to nonstudy COVID-19 vaccination (AZD1222, n = 19,569; placebo, n = 8868), with censoring for nonstudy COVID-19 vaccination, regardless of unblinding. (B) Incidence of SARS-CoV-2 RT-PCR–positive symptomatic illness events and decrease in the at-risk population over time from first dose during the period to nonstudy COVID-19 vaccination. The at-risk population curves show the numbers of participants in the FVAS who have not been censored and were available for analysis at the corresponding time point. Cumulative incidence of (C) severe or critical symptomatic COVID-19 and (D) SARS-CoV-2 infection, as defined by seroconversion rate from negative at baseline to positive for SARS-CoV-2 nucleocapsid antibody at 15 or more days after the second dose, regardless of symptoms, in the FVAS population for the period to nonstudy COVID-19 vaccination (AZD1222, n = 19,569; placebo, n = 8868), with censoring for nonstudy COVID-19 vaccination, regardless of unblinding. For panels A, C, and D, time to first event was from time of second dose administration, calculated as follows: (date of SARS-CoV-2-positive test) – (date of second dose of AZD1222 or placebo + 14 days) + 1. For censored participants, censoring time was from date of second dose of AZD1222 or placebo plus 14 days to the last time observed before data cutoff (July 30, 2021). Cumulative incidences were estimated using the Kaplan-Meier method. Cumulative incidence curves were truncated at the point at which less than 10% of the starting population remained at risk. IR, incidence rate per 1000 person years.