Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: A substudy of two randomised controlled trials (COV001 and COV002)
The Lancet — Flaxman A, Marchevsky NG, Jenkin D, et al. | September 13, 2021
An extended interval before the second dose of ChAdOx1 nCoV-19 results in higher antibody titres. The third dosage of ChAdOx1 nCoV-19 generates antibodies to levels consistent with high effectiveness after the second dose and enhances T-cell responses.
Between March 11 and 21, 2021, 90 candidates were registered in the third-dose boost substudy, of whom 80 (89%) were assessable for reactogenicity, 75 (83%) were assessable for evaluation of antibodies, and 15 (17%) were assessable for T-cells responses.
The two-dose cohort involved 321 candidates who had reactogenicity data (with a prime-boost interval of 8–12 weeks: 267 [83%] of 321; 15–25 weeks: 24 [7%]; or 44–45 weeks: 30 [9%]) and 261 who had immunogenicity data (interval of 8–12 weeks: 115 [44%] of 261; 15–25 weeks: 116 [44%]; and 44–45 weeks: 30 [11%]).
Antibody titres recorded 320 days after vaccination following a single dose remained greater than titres measured at baseline.
Thirty-two candidates received a late second dose of vaccine 44–45 weeks after the first dose, of whom 30 were involved in immunogenicity and reactogenicity analyses.
Antibody titres were higher 28 days after vaccination in individuals who had a longer delay between the first and second doses compared with those who had a shorter interval.
Antibody titres were substantially greater 28 days after the third dose among individuals who got the third dose of vaccine than 28 days after a second dose.
T-cell responses were also improved after the third dosage (median response increased from 200 spot forming units [SFUs] per million peripheral blood mononuclear cells [PBMCs; IQR 127–389] shortly before the third dose to 399 SFUs per milion PBMCs [314–662] by day 28 after the third dose; Wilcoxon signed rank test).
The reactogenicity of a late second or third dose was lower than the reactogenicity of a first dose.
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