Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination : Secondary analysis of the randomised CombiVacS study
García-Pérez, Javier (Instituto de Salud Carlos III)
González-Pérez, María (Instituto de Salud Carlos III)
Castillo de la Osa, María (Instituto de Salud Carlos III)
Borobia, Alberto M. (Universidad Autónoma de Madrid)
Castaño, Luis (Hospital Universitario de Cruces (Barakaldo, País Basc))
Bertrán, María Jesús (Hospital Clínic i Provincial de Barcelona)
Campins Martí, Magda (Hospital Universitari Vall d'Hebron)
Portolés, Antonio (Universidad Complutense de Madrid)
Lora, David (Universidad Complutense de Madrid)
Bermejo, Mercedes (Instituto de Salud Carlos III)
Conde, Patricia (Instituto de Salud Carlos III)
Hernández-Gutierrez, Lourdes (Instituto de Salud Carlos III)
Carcas, Antonio (Hospital Universitario La Paz (Madrid))
Arana-Arri, Eunate (Hospital Universitario de Cruces (Barakaldo, País Basc))
Tortajada, Marta (Hospital Clínic i Provincial de Barcelona)
Fuentes Camps, Inmaculada (Hospital Universitari Vall d'Hebron)
Ascaso, Ana (Hospital Clínico San Carlos (Madrid))
García-Morales, María Teresa (Universidad Complutense de Madrid)
Erick de la Torre-Tarazona, Humberto (Instituto de Salud Carlos III)
Arribas, Jose (Hospital Universitario La Paz (Madrid))
Imaz-Ayo, Natale (Hospital Universitario de Cruces (Barakaldo, País Basc))
Mellado-Pau, Eugènia (Hospital Clínic i Provincial de Barcelona)
Agustí Escasany, M. Antònia (Hospital Universitari Vall d'Hebron)
Pérez-Ingidua, Carla (Hospital Clínico San Carlos (Madrid))
Gómez de la Cámara, Agustín (Universidad Complutense de Madrid)
Ochando, Jordi (Instituto de Salud Carlos III)
Belda-Iniesta, Cristobal (Instituto de Salud Carlos III)
Frías, Jesús (Hospital Universitario La Paz (Madrid))
Alcami, Jose (Instituto de Salud Carlos III)
Pérez-Olmeda, Mayte (Instituto de Salud Carlos III)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	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. 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). 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). 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).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Antibodies ; Heterologous vaccination ; Neutralisation ; SARS-CoV-2 ; Variants
Publicat a:	EClinicalMedicine, Vol. 50 (july 2022) , ISSN 2589-5370

DOI: 10.1016/j.eclinm.2022.101529
PMID: 35795713

14 p, 1.7 MB

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