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

Autor:	García-Pérez, Javier, Gonzalez-Perez, Maria, Castillo de la Osa, María, Borobia, Alberto M, Castaño, Luis, Bertrán, María Jesús, Campins, Magdalena, Portolés, Antonio, Lora, David, Bermejo, Mercedes, Conde-San Román, Patricia, Hernandez, Lourdes, Carcas, Antonio, Arana-Arri, Eunate, Tortajada, Marta, Fuentes, Inmaculada, Ascaso, Ana, García-Morales, María Teresa, de la Torre-Tarazona, Humberto Erick, Arribas, José-Ramón, Imaz-Ayo, Natale, Mellado-Pau, Eugènia, Agustí, Antonia, Pérez-Ingidua, Carla, Gómez de la Cámara, Agustín, Ochando, Jordi, Belda-Iniesta, Cristobal, Frías, Jesús, Alcamí, José, Perez-Olmeda, Mayte, CombiVacS study Group
Přispěvatelé:	Instituto de Salud Carlos III, Plan Nacional de I+D+i (España), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Unión Europea. Comisión Europea. H2020, Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas), European Commission, Institut Català de la Salut, [García-Pérez J] Unidad de Inmunopatología del SIDA, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [González-Pérez M] Laboratorio de Referencia en Inmunología, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Castillo de la Osa M] Laboratorio de Serología, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Borobia AM] Servicio de Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain. [Castaño L] Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, Barakaldo, Spain. [Bertrán MJ] Servicio de Medicina Preventiva y Epidemiologia, Hospital Clínic de Barcelona, Barcelona, Spain. [Campins M] Servei de Medicina Preventiva i Epidemiologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Fuentes I] Unitat de Suport a la Investigació Clínica, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Agustí A] Servei de Farmacologia Clínica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Departament de Farmacologia, Terapèutica i Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus
Rok vydání:	2022
Předmět:	Otros calificadores::Otros calificadores::/prevención & control [Otros calificadores] variants COVID-19 (Malaltia) - Prevenció SARS-CoV-2 Variants Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] heterologous vaccination General Medicine Amino Acids Peptides and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies Neutralizing [CHEMICALS AND DRUGS] Antibodies Neutralisation Other subheadings::Other subheadings::/prevention & control [Other subheadings] neutralisation Heterologous vaccination virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] antibodies fenómenos del sistema inmunitario::formación de anticuerpos::inmunogenicidad vacunal [FENÓMENOS Y PROCESOS] Immune System Phenomena::Antibody Formation::Immunogenicity Vaccine [PHENOMENA AND PROCESSES] Immunoglobulines aminoácidos péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos neutralizantes [COMPUESTOS QUÍMICOS Y DROGAS] COVID-19 (Malaltia) - Vacunació
Zdroj:	Scientia
ISSN:	2589-5370 2021-0019
Popis:	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 < 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. 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. Funded by Instituto de Salud Carlos III (ISCIII). AMB, AJC, JO, and JF are members of the VACCELERATE (European Corona Vaccine Trial Accelerator Platform) Network, which aims to facilitate and accelerate the design and implementation of COVID-19 phase 2 and 3 vaccine trials. JO is a member of the INsTRuCT (Innovative Training in Myeloid Regulatory Cell Therapy) Consortium, a network of European scientists from academia and industry focused on developing innovative immunotherapies. 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), the State Plan for Research, Development, and Innovation 2013−16, the State Plan for Scientific and Technical Research and Innovation 2017−20, and the Subdirectorate General for Evaluation and Promotion of Research, Instituto de Salud Carlos III, cofinanced with FEDER funds. CombiVacS was designed under the umbrella of the VACCELERATE project. VACCELER ATE and INsTRuCT received funding from the EU’s Horizon 2020 Research and Innovation Programme (grant agreement numbers 101037867 and 860003). The Instituto de Salud Carlos III is the Spanish partner in the VACCELERATE project. 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) “A way to make Europe”. The authors thank all trial participants, the international data safety monitoring board (Appendix 1 p 23), and the trial steering committee (Appendix 1 pp 24−25). The authors thank Esther Prieto for editorial assistance and writing support (employed by Hospital Universitario La Paz; funded by the Instituto de Salud Carlos III, grant number PCT20/00018) and María Castillo-de la Osa (PEJ2018-004557-A) for excellent technical assistance. Sí
Databáze:	OpenAIRE
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