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Effects of Short-Term Corticosteroid Use on Reactogenicity and Immunogenicity of the First Dose of ChAdOx1 nCoV-19 Vaccine.

ABSTRACT: The effects of corticosteroid use on the reactogenicity and immunogenicity of ChAdOx1 nCoV-19 (ChAd) vaccine were evaluated. Healthcare workers (HCWs) who took low-dose corticosteroid agents around the time of the first dose of ChAd (ChAdPd group) were recruited and the reactogenicity and immunogenicity were compared with those of ChAd (ChAd group) and BNT162b2 vaccination (BNT group) of HCWs without corticosteroid exposure. The immunogenicity was measured three weeks after vaccination using quantitative anti-SARS-CoV-2 spike protein (S) antibody electrochemiluminescence immunoassay and interferon gamma (IFN-γ) release assay. A total of 67 HCWs comprising 24 ChAd, 29 BNT, and 14 ChAdPd was included. The median total corticosteroid dose of the ChAdPd group was 30 mg prednisolone equivalents (interquartile range (IQR) 20-71.3 mg). HCWs in the ChAdPd group experienced significantly milder reactogenicity (median total score 7.5, IQR 4.0-18.0) compared to those in the ChAd group (median 23.0, IQR 8.0-43.0, P=0.012) but similar to that in the BNT group (median 5.0, IQR 3.0-9.0, P=0.067). The S antibody concentration of the ChAdPd group (62.4 ± 70.0 U/mL) was higher than that of the ChAd group, though without statistical significance (3.45 ± 57.6 U/mL, P=0.192). The cellular immune response was most robust in the ChAdPd group, with significantly higher IFN-γ concentration (5.363 ± 4.276 IU/mL), compared to the ChAd (0.978 ± 1.181 IU/mL, P=0.002) and BNT (1.656 ± 1.925 IU/mL, P=0.009) groups. This finding suggest that short-term corticosteroid reduces reactogenicity of the first dose of ChAd without hindering immunogenicity.

SUBMITTER: Yang J

PROVIDER: S-EPMC8493039 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Fractional dose is an important strategy to increase access to vaccines. This study evaluated the effectiveness, safety, and immunogenicity of half dose of ChAdOx1 nCoV-19 vaccine. A non-inferiority non-randomized controlled trial compared a half dose of ChAdOx1 nCoV-19 with the full dose, with an interval of 8 to 10 weeks, in individuals aged 18-49 years. The primary endpoints were the incidence rate of new cases/1,000 person-year at 90 days after 14 days of the second dose, confirmed by RT-PCR and new cases registered at SUS National Health Surveillance Database (e-SUS VS). The anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) by chemiluminescence and the neutralizing antibodies by plaque reduction neutralization test (PRNT) were titrated. The soluble biomarkers were quantified with a multiplex immunoassay. Follow-up was 90 days after 14 days of the second dose. A total of 29,598 individuals were vaccinated. After exclusion, 16,570 individuals who received half a dose and 6,402 who received full doses were analyzed. The incidence of new cases confirmed by RT-PCR of half dose was non-inferior to full dose (23.7 vs. 25.7 cases per 1,000 persons-year [coefficient group -0.09 CI95%(-0.49 to 0.31)], even after adjusting for age and sex. There were no deaths or hospitalization after immunization of either group. Immunogenicity was evaluated in a subsample (N=558) compared to 154 healthcare workers who received a full dose. The seroconversion rate in seronegative individuals at baseline half dose was 99.8%, similar to that of the full dose (100%). Geometric mean concentration (95% CI; BAU/mL) were half dose = 188 (163-217) and full dose = 529 (423-663) (p < 0.001). In seropositive subjects at baseline (pre-immune individuals), the first dose induced very high and similar IgG-S in half dose 1,359 (1,245-1,483) and full dose 1,354 (1,048-1,749) BAU/mL. A half dose induced a high increase in plasma chemokines, pro-inflammatory/regulatory cytokines, and growth factors. The frequency of adverse events was similar. No serious adverse events or deaths were reported. A half dose of ChAdOx1 nCoV-19 is as effective, safe, and immunogenic as the full dose. The immune response in pre-immune (seropositive in the baseline) individuals indicates that the half dose may be a booster dose schedule.

Project description:BackgroundHeterologous vaccine regimens have been widely discussed as a way to mitigate intermittent supply shortages and to improve immunogenicity and safety of COVID-19 vaccines. We aimed to assess the reactogenicity and immunogenicity of heterologous immunisations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNtech, Mainz, Germany) compared with homologous BNT162b2 and ChAdOx1 nCov-19 immunisation.MethodsThis is an interim analysis of a prospective observational cohort study enrolling health-care workers in Berlin (Germany) who received either homologous ChAdOx1 nCov-19 or heterologous ChAdOx1 nCov-19-BNT162b2 vaccination with a 10-12-week vaccine interval or homologous BNT162b2 vaccination with a 3-week vaccine interval. We assessed reactogenicity after the first and second vaccination by use of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was measured by the presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG), by an RBD-ACE2 binding inhibition assay (surrogate SARS-CoV-2 virus neutralisation test), a pseudovirus neutralisation assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), and anti-S1-IgG avidity. T-cell reactivity was measured by IFN-γ release assay.FindingsBetween Dec 27, 2020, and June 14, 2021, 380 participants were enrolled in the study, with 174 receiving homologous BNT162b2 vaccination, 38 receiving homologous ChAdOx1 nCov-19 vaccination, and 104 receiving ChAdOx1 nCov-19-BNT162b2 vaccination. Systemic symptoms were reported by 103 (65%, 95% CI 57·1-71·8) of 159 recipients of homologous BNT162b2, 14 (39%, 24·8-55·1) of 36 recipients of homologous ChAdOx1 nCov-19, and 51 (49%, 39·6-58·5) of 104 recipients of ChAdOx1 nCov-19-BNT162b2 after the booster immunisation. Median anti-RBD IgG levels 3 weeks after boost immunisation were 5·4 signal to cutoff ratio (S/co; IQR 4·8-5·9) in recipients of homologous BNT162b2, 4·9 S/co (4·3-5·6) in recipients of homologous ChAdOx1 nCov-19, and 5·6 S/co (5·1-6·1) in recipients of ChAdOx1 nCov-19- BNT162b2. Geometric mean of 50% inhibitory dose against alpha and beta variants were highest in recipients of ChAdOx1 nCov-19-BNT162b2 (956·6, 95% CI 835·6-1095, against alpha and 417·1, 349·3-498·2, against beta) compared with those in recipients of homologous ChAdOx1 nCov-19 (212·5, 131·2-344·4, against alpha and 48·5, 28·4-82·8, against beta; both p<0·0001) or homologous BNT162b2 (369·2, 310·7-438·6, against alpha and 72·4, 60·5-86·5, against beta; both p<0·0001). SARS-CoV-2 S1 T-cell reactivity 3 weeks after boost immunisation was highest in recipients of ChAdOx1 nCov-19-BNT162b2 (median IFN-γ concentration 4762 mIU/mL, IQR 2723-8403) compared with that in recipients of homologous ChAdOx1 nCov-19 (1061 mIU/mL, 599-2274, p<0·0001) and homologous BNT162b2 (2026 mIU/mL, 1459-4621, p=0·0008) vaccination.InterpretationThe heterologous ChAdOx1 nCov-19-BNT162b2 immunisation with 10-12-week interval, recommended in Germany, is well tolerated and improves immunogenicity compared with homologous ChAdOx1 nCov-19 vaccination with 10-12-week interval and BNT162b2 vaccination with 3-week interval. Heterologous prime-boost immunisation strategies for COVID-19 might be generally applicable.FundingForschungsnetzwerk der Universitätsmedizin zu COVID-19, the German Ministry of Education and Research, Zalando SE.

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Effects of Short-Term Corticosteroid Use on Reactogenicity and Immunogenicity of the First Dose of ChAdOx1 nCoV-19 Vaccine.

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