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2.
Open forum infectious diseases ; 8(Suppl 1):S804-S804, 2021.
Article in English | EuropePMC | ID: covidwho-1564836

ABSTRACT

Background SARS-CoV-2 vaccine efficacy (VE) against asymptomatic infection and impact on viral shedding during breakthrough infections have critical implications for pandemic control. AZD1222 (ChAdOx1 nCoV-19;2 doses, 4 weeks apart) demonstrated VE of 74.0% (95% CI 65.3, 80.5) against the primary endpoint of symptomatic RT-PCR-confirmed COVID-19 and safety in a Phase 3, 2:1 randomized, placebo-controlled study in the US, Chile and Peru (n=32,451). Here we present exploratory analyses on asymptomatic infections determined by nucleocapsid (N) seroconversion and time to viral clearance in participants with symptomatic infections determined by N seroconversion (primary data cut, March 5, 2021). Methods N seroconversion was assessed at all scheduled and illness visits in the fully vaccinated analysis set (Table). In this analysis, symptomatic infections are defined as N seroconversion ≥ 15 days post second dose in participants who attended an illness visit with ≥ 1 qualifying COVID-19 symptom and had ≥ 1 positive RT-PCR result for SARS-CoV-2. Asymptomatic infections are defined as N seroconversion ≥ 15 days post second dose in participants who did not meet the criteria for symptomatic infections. In participants with symptomatic infections, viral shedding in saliva was assessed for 28 days and cumulative incidence of viral clearance was determined. Table. AZD1222 VE against symptomatic and potentially asymptomatic SARS-CoV-2 infections as determined by N seroconversion Results Overall, 358 participants had SARS-CoV-2 infections as determined by N seroconversion (Table). Incidences per 1000 person-years of symptomatic infections were 25.62 for AZD1222 vs 103.42 for placebo (VE 75.23%;95% CI 65.33, 82.31) and of asymptomatic infections were 51.24 vs 111.95 (VE 54.24%;95% CI 39.99, 65.10) (Table). Sensitivity analyses for N seroconversion using the primary endpoint and CDC criteria for defining symptomatic/asymptomatic status were supportive. Median time to viral clearance in saliva in participants with symptomatic infections was 11 days (AZD1222, n=52) vs 16 days (placebo, n=92) (Figure). Figure. Viral clearance in saliva samples in participants with symptomatic infections as determined by N seroconversion Conclusion AZD1222 resulted in lower yet meaningful VE against asymptomatic compared to symptomatic infections, as determined by N seroconversion, and shortened viral shedding in symptomatic SARS-CoV-2 breakthrough infections vs placebo, highlighting its potential contribution to reducing viral transmission. Funding Statement Disclosures Ann R. Falsey, MD, AstraZeneca (Individual(s) Involved: Self): Grant/Research Support;BioFire Diagnostics (Individual(s) Involved: Self): Grant/Research Support;Janssen (Individual(s) Involved: Self): Grant/Research Support;Merck, Sharpe and Dohme (Individual(s) Involved: Self): Grant/Research Support;Novavax (Individual(s) Involved: Self): Other Financial or Material Support, Paid DSMB member;Pfizer (Individual(s) Involved: Self): Grant/Research Support Merlin L. Robb, M.D., Henry M. Jackson Foundation (Other Financial or Material Support, This work was conducted under a funding agreement with the USG through an INteragency Personnel Agreement) Hong-Van Tieu, M.D, M.S., National Institutes of Health (Grant/Research Support) Lawrence Corey, MD, NIH (Grant/Research Support) Kathleen Neuzil, MD, MPH, NIH (Grant/Research Support, Other Financial or Material Support, Dr. Neuzil is the CoVPN co-chair with testing of COVID-19 vaccines with salary support from NIH.)Pfizer (Grant/Research Support) Jill Maaske, M.D., AstraZeneca (Employee, Shareholder) Brett Jepson, n/a, AstraZeneca (Other Financial or Material Support, On assignment to AstraZeneca)Cytel, Inc. (Employee) Stephanie Sproule, n/a, AstraZeneca (Other Financial or Material Support, Fees for statistical consulting.) Elizabeth Kelly, n/a, AstraZeneca (Employee, Shareholder)

3.
Nat Med ; 27(11): 2032-2040, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526097

ABSTRACT

The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , Immunity, Humoral , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Asymptomatic Infections , COVID-19/immunology , COVID-19/pathology , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Cohort Studies , Female , Humans , Immunization, Secondary , Infection Control/statistics & numerical data , Male , Middle Aged , Patient Acuity , SARS-CoV-2/genetics , Treatment Outcome , United Kingdom/epidemiology , Vaccination , Young Adult
4.
Nat Med ; 27(11): 2032-2040, 2021 11.
Article in English | MEDLINE | ID: covidwho-1442795

ABSTRACT

The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , Immunity, Humoral , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Asymptomatic Infections , COVID-19/immunology , COVID-19/pathology , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Cohort Studies , Female , Humans , Immunization, Secondary , Infection Control/statistics & numerical data , Male , Middle Aged , Patient Acuity , SARS-CoV-2/genetics , Treatment Outcome , United Kingdom/epidemiology , Vaccination , Young Adult
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