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Immunogenic Dynamics and SARS-CoV-2 Variants Neutralization of the Heterologous ChAdOx1-S/BNT162b2 Vaccination: Secondary Analysis of the CombiVacS Study

82 Pages Posted: 25 Mar 2022

See all articles by José Alcamí Pertejo

José Alcamí Pertejo

Carlos III Institute of Health - AIDS Immunopathogenesis Unit

Javier García-Pérez

Carlos III Institute of Health - CIBER de Epidemiología y Salud Pública (CIBERESP)

Maria Gonzalez-Perez

Carlos III Institute of Health - National Centre for Microbiology

María Castillo de la Osa

Carlos III Institute of Health

Alberto M Borobia

La Paz University Hospital - Servicio de Farmacología Clínica

Luis Castaño

University of the Basque Country - Biocruces Bizkaia Health Research Institute

María Jesús Bertrán

Hospital Clinic of Barcelona - Preventive Medicine and Epidemiology Service

Magdalena Campins

Hospital Vall d’Hebron - Servicio de Medicina Preventiva y Epidemiología

Antonio Portolés

Instituto de Investigación Sanitaria San Carlos (IdISSC) - Servicio de Farmacología Clínica

David Lora

Instituto de Investigación Sanitaria Hospital "12 de Octubre" - Hospital Universitario 12 de Octubre

Mercedes Bermejo

Carlos III Institute of Health - National Centre for Microbiology

Patricia Conde

Carlos III Institute of Health - National Centre for Microbiology

Lourdes Hernández Gutiérrez

Carlos III Institute of Health

Antonio J Carcas

La Paz University Hospital - Servicio de Farmacología Clínica

Eunate Arana-Arr

Hospital Universitario Cruces

Marta Tortajada

Hospital Clínic de Barcelona

Inmaculada Fuentes-Camps

Institut de Recerca Hospital Universitari Vall d’Hebron (VHIR) - Unidad de Soporte a la Investigación Clínica

Ana Ascaso

Universidad Complutense de Madrid (UCM) - Servicio de Farmacología Clínica

María Teresa García-Morales

Instituto de Investigación Sanitaria Hospital "12 de Octubre" - Hospital Universitario 12 de Octubre

Humberto Erick de la Torre-Tarazona

Carlos III Institute of Health

José-Ramón Arribas

Carlos III Institute of Health

Natale Imaz-Ayo

University of the Basque Country - Biocruces Bizkaia Health Research Institute

Eugènia Mellado-Pau

Hospital Clínic de Barcelona

Antonia Agustí

Autonomous University of Barcelona - Servicio de Farmacología Clínica

Carla Pérez-Ingidua

Instituto de Investigación Sanitaria San Carlos (IdISSC) - Servicio de Farmacología Clínica

Agustín Gómez de la Cámara

Instituto de Investigación Sanitaria Hospital "12 de Octubre" - Hospital Universitario 12 de Octubre

Jordi Ochando

Carlos III Institute of Health - Laboratorio de Referencia en Inmunología

Cristóbal Belda-Iniesta

Carlos III Institute of Health

Jesús Frías

La Paz University Hospital - Servicio de Farmacología Clínica

Mayte Pérez-Olmeda

Carlos III Institute of Health - National Centre for Microbiology

CombiVacS Study Group

Independent

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Multiple version iconThere are 2 versions of this paper

Abstract

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. This study was registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739).

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.

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.

Suggested Citation

Alcamí Pertejo, José and García-Pérez, Javier and Gonzalez-Perez, Maria and Castillo de la Osa, María and Borobia, Alberto M and Castaño, Luis and Jesús Bertrán, María and Campins, Magdalena and Portolés, Antonio and Lora, David and Bermejo, Mercedes and Conde, Patricia and Hernández Gutiérrez, Lourdes and Carcas, Antonio J and Arana-Arr, Eunate and Tortajada, Marta and Fuentes-Camps, Inmaculada and Ascaso, Ana and García-Morales, María Teresa and de la Torre-Tarazona, Humberto Erick and Arribas, José-Ramón and Imaz-Ayo, Natale and Mellado-Pau, Eugènia and Agustí, Antonia and Pérez-Ingidua, Carla and Gómez de la Cámara, Agustín and Ochando, Jordi and Belda-Iniesta, Cristóbal and Frías, Jesús and Pérez-Olmeda, Mayte and Group, CombiVacS Study, Immunogenic Dynamics and SARS-CoV-2 Variants Neutralization of the Heterologous ChAdOx1-S/BNT162b2 Vaccination: Secondary Analysis of the CombiVacS Study (2/25/2022). Available at SSRN: https://ssrn.com/abstract=4066707 or http://dx.doi.org/10.2139/ssrn.4066707

José Alcamí Pertejo (Contact Author)

Carlos III Institute of Health - AIDS Immunopathogenesis Unit ( email )

c/ Monforte de Lemos 5
Madrid, Madrid 28029
Spain

Javier García-Pérez

Carlos III Institute of Health - CIBER de Epidemiología y Salud Pública (CIBERESP) ( email )

Monforte de Lemos 5
Madrid
Spain

Maria Gonzalez-Perez

Carlos III Institute of Health - National Centre for Microbiology

Monforte de Lemos 5
Madrid, Madrid 28029
Spain

María Castillo de la Osa

Carlos III Institute of Health ( email )

c/ Monforte de Lemos 5
Madrid, Madrid 28029
Spain

Alberto M Borobia

La Paz University Hospital - Servicio de Farmacología Clínica ( email )

Madrid
Spain

Luis Castaño

University of the Basque Country - Biocruces Bizkaia Health Research Institute ( email )

Spain

María Jesús Bertrán

Hospital Clinic of Barcelona - Preventive Medicine and Epidemiology Service ( email )

Barcelona, 08036
Spain

Magdalena Campins

Hospital Vall d’Hebron - Servicio de Medicina Preventiva y Epidemiología ( email )

Barcelona
Spain

Antonio Portolés

Instituto de Investigación Sanitaria San Carlos (IdISSC) - Servicio de Farmacología Clínica ( email )

Madrid
Spain

David Lora

Instituto de Investigación Sanitaria Hospital "12 de Octubre" - Hospital Universitario 12 de Octubre ( email )

Madrid
Spain

Mercedes Bermejo

Carlos III Institute of Health - National Centre for Microbiology ( email )

Patricia Conde

Carlos III Institute of Health - National Centre for Microbiology ( email )

Lourdes Hernández Gutiérrez

Carlos III Institute of Health ( email )

Antonio J Carcas

La Paz University Hospital - Servicio de Farmacología Clínica ( email )

Madrid
Spain

Eunate Arana-Arr

Hospital Universitario Cruces

Marta Tortajada

Hospital Clínic de Barcelona

Inmaculada Fuentes-Camps

Institut de Recerca Hospital Universitari Vall d’Hebron (VHIR) - Unidad de Soporte a la Investigación Clínica ( email )

Barcelona
Spain

Ana Ascaso

Universidad Complutense de Madrid (UCM) - Servicio de Farmacología Clínica ( email )

Carretera de Humera s/n
Madrid, Madrid 28223
Spain

María Teresa García-Morales

Instituto de Investigación Sanitaria Hospital "12 de Octubre" - Hospital Universitario 12 de Octubre ( email )

Madrid
Spain

Humberto Erick De la Torre-Tarazona

Carlos III Institute of Health ( email )

José-Ramón Arribas

Carlos III Institute of Health

Natale Imaz-Ayo

University of the Basque Country - Biocruces Bizkaia Health Research Institute ( email )

Spain

Eugènia Mellado-Pau

Hospital Clínic de Barcelona ( email )

Antonia Agustí

Autonomous University of Barcelona - Servicio de Farmacología Clínica ( email )

Plaça Cívica
Cerdañola del Valles
Barcelona, Barcelona 08193
Spain

Carla Pérez-Ingidua

Instituto de Investigación Sanitaria San Carlos (IdISSC) - Servicio de Farmacología Clínica ( email )

Madrid
Spain

Agustín Gómez de la Cámara

Instituto de Investigación Sanitaria Hospital "12 de Octubre" - Hospital Universitario 12 de Octubre

Madrid
Spain

Jordi Ochando

Carlos III Institute of Health - Laboratorio de Referencia en Inmunología

c/ Monforte de Lemos 5
Madrid, Madrid 28029
Spain

Cristóbal Belda-Iniesta

Carlos III Institute of Health ( email )

c/ Monforte de Lemos 5
Madrid, Madrid 28029
Spain

Jesús Frías

La Paz University Hospital - Servicio de Farmacología Clínica ( email )

Madrid
Spain

Mayte Pérez-Olmeda

Carlos III Institute of Health - National Centre for Microbiology

Monforte de Lemos 5
Madrid, Madrid 28029
Spain

CombiVacS Study Group

Independent

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