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 LancetFlaxman 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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