Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact firstname.lastname@example.org.
Immunogenic Dynamics and SARS-CoV-2 Variants Neutralization of the Heterologous ChAdOx1-S/BNT162b2 Vaccination: Secondary Analysis of the CombiVacS Study
39 Pages Posted: 21 Mar 2022More...
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: 676 adult subjects primed with ChAdOx1-S were randomised to receive BNT162b2 as second dose (interventional group [IG]) or no vaccine (control group [CG]). Subjects 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.
Findings: In this secondary analysis, 664 subjects (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 < 0·0001). RBD antibodies titres decreased at day 180 (1142·0 BAU/mL [1048·69–1243·62] and 1836·4 BAU/mL [1621·62–2079·62] in the IG and CG, respectively; p < 0·0001). Neutralising antibodies also waned from day 28 to day 180 in both the IG (1429·01 [1220·37–1673·33] and 198·72 [161·54–244·47], respectively) and the CG (1503·28 [1210·71–1866·54] and 295·57 [209·84–416·33], respectively). The lowest variant-specific response was observed against Omicron-and Beta variants, with low proportion of individuals exhibiting specific neutralising antibody titres (NT50) >1:100 at day 180 (19% and 22%, respectively).
Interpretation: Titres of RBD antibodies decay over time, similar to homologous regimes. Delaying administration of the second dose did not have a detrimental effect and may have improved the response obtained. Lower neutralisation was observed against Omicron and Beta variants at day 180.
Trial Registration Details: This study was registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739).
Funding Information: This work is funded by Instituto de Salud Carlos III, a Spanish public body assigned to the Ministry of Science and Innovation that manages and promotes public clinical research related to public health. The Spanish Clinical Trials Platform is a public network funded by the Instituto de Salud Carlos III (grant numbers PTC20/00018 and PT17/0017).
CombiVacS was designed under the umbrella of the VACCELERATE project. VACCELERATE and INsTRuCT received funding from the EU’s Horizon 2020 Research and Innovation Programme (grant agreement numbers 101037867 and 860003).
This work is partially funded by Institute of Health Carlos III (Instituto de Salud Carlos III – ISCIII –), (grants PI19CIII/00004 to JA and PI21CIII/00025 to MPO and JGP), and COVID-19 FUND (grants COV20/00679 and COV20/00072 to MPO and JA) and CIBERINFEC, co-financed by the European Regional Development Fund (FEDER).
Declaration of Interests: JA has received fees for educational programs from Gilead, MSD, GSK and Janssen outside of the submitted work. MC has participated in advisory boards and has received research funding from GSK, Sanofy Pasteur, Pfizer, Novavax and Janssen.CB-I is the deputy general manager of the Instituto de Salud Carlos III. JRA has received fees from Janssen, outside of the submitted work. AMB is principal investigator of clinical trials sponsored by GlaxoSmithKline, Daiichi-Sankyo, Janssen, and Farmalider, outside of the submitted work. All other authors declare no competing interests.
Ethics Approval Statement: The trial complies with the principles of the Declaration of Helsinki and Good Clinical Practice. This study was approved by the Spanish Agency of Medicines and Healthcare Products (AEMPS) and by the Ethics Committee at University Hospital La Paz.
Keywords: SARS-CoV-2, heterologous vaccination, Neutralisation, Variants, antibodies
Suggested Citation: Suggested Citation