EClinicalMedicine (Aug 2022)

Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study

  • Javier García-Pérez,
  • María González-Pérez,
  • María Castillo de la Osa,
  • Alberto M. Borobia,
  • Luis Castaño,
  • María Jesús Bertrán,
  • Magdalena Campins,
  • Antonio Portolés,
  • David Lora,
  • Mercedes Bermejo,
  • Patricia Conde,
  • Lourdes Hernández-Gutierrez,
  • Antonio Carcas,
  • Eunate Arana-Arri,
  • Marta Tortajada,
  • Inmaculada Fuentes,
  • Ana Ascaso,
  • María Teresa García-Morales,
  • Humberto Erick de la Torre-Tarazona,
  • José-Ramón Arribas,
  • Natale Imaz-Ayo,
  • Eugènia Mellado-Pau,
  • Antonia Agustí,
  • Carla Pérez-Ingidua,
  • Agustín Gómez de la Cámara,
  • Jordi Ochando,
  • Cristobal Belda-Iniesta,
  • Jesús Frías,
  • José Alcamí,
  • Mayte Pérez-Olmeda

Journal volume & issue
Vol. 50
p. 101529

Abstract

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Summary: Background: The CombiVacS study was designed to assess immunogenicity and reactogenicity of the heterologous ChAdOx1-S/BNT162b2 combination, and 14-day results showed a strong immune response. The present secondary analysis addresses the evolution of humoral and cellular response up to day 180. Methods: Between April 24 and 30, 2021, 676 adults primed with ChAdOx1-S were enrolled in five hospitals in Spain, and randomised to receive BNT162b2 as second dose (interventional group [IG]) or no vaccine (control group [CG]). Individuals from CG received BNT162b2 as second dose and also on day 28, as planned based on favourable results on day 14. Humoral immunogenicity, measured by immunoassay for SARS-CoV-2 receptor binding domain (RBD), antibody functionality using pseudovirus neutralisation assays for the reference (G614), Alpha, Beta, Delta, and Omicron variants, as well as cellular immune response using interferon-γ and IL-2 immunoassays were assessed at day 28 after BNT162b2 in both groups, at day 90 (planned only in the interventional group) and at day 180 (laboratory data cut-off on Nov 19, 2021). This study was registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739). Findings: In this secondary analysis, 664 individuals (441 from IG and 223 from CG) were included. At day 28 post vaccine, geometric mean titres (GMT) of RBD antibodies were 5616·91 BAU/mL (95% CI 5296·49–5956·71) in the IG and 7298·22 BAU/mL (6739·41–7903·37) in the CG (p 1:100 at day 180 (19% and 22%, respectively). Interpretation: Titres of RBD antibodies decay over time, similar to homologous regimes. Our findings suggested that delaying administration of the second dose did not have a detrimental effect after vaccination and may have improved the response obtained. Lower neutralisation was observed against Omicron and Beta variants at day 180. Funding: Funded by Instituto de Salud Carlos III (ISCIII).

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