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Reactogenicity and Immunogenicity of BNT162b2 in Subjects Having Received a First Dose of ChAdOx1s: Initial Results of a Randomised, Adaptive, Phase 2 Trial (CombiVacS)

38 Pages Posted: 27 May 2021

See all articles by Alberto M Borobia

Alberto M Borobia

La Paz University Hospital - Servicio de Farmacología Clínica

Antonio J Carcas

La Paz University Hospital - Servicio de Farmacología Clínica

María Teresa Pérez Olmeda

Carlos III Institute of Health - Laboratorio de Serología

Luis Castaño

University of the Basque Country - Biocruces Bizkaia Health Research Institute

María Jesús Bertrán

Hospital Clinic of Barcelona - Preventive Medicine and Epidemiology Service

Javier García-Pérez

Universidad Carlos III de Madrid - Unidad de Inmunopatología del SIDA

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

Maria Gonzalez-Perez

Carlos III Institute of Health - National Centre for Microbiology

María Teresa García Morales

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

Eunate Arana

Cruces University Hospital - Biocruces Bizkaia Health Research Institute

Marta Aldea Novo

Hospital Clinic of Barcelona - Preventive Medicine and Epidemiology Service

Francisco Díez-Fuertes

Carlos III Institute of Health - Laboratorio de Serología

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

David Lora

University Hospital 12 de Octubre

Natale Imaz-Ayo

University of the Basque Country - Biocruces Bizkaia Health Research Institute

Lourdes E Baron-Mira

Hospital Clinic of Barcelona - Preventive Medicine and Epidemiology Service

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

JR Arribas

Universidad Autónoma de Madrid - Hospital Universitario La Paz. IdiPAZ

Jordi Ochando

Carlos III Institute of Health - Laboratorio de Referencia en Inmunología

José Alcamí Pertejo

Carlos III Institute of Health - Unidad de Inmunopatología del SIDA

Cristóbal Belda-Iniesta

Carlos III Institute of Health

Jesús Frías

La Paz University Hospital - Servicio de Farmacología Clínica

CombiVacS Study Group

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Abstract

Background: There are no immunological data on SARS-CoV-2 heterologous vaccinations schedules in humans. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, Astra Zeneca).

Methods: We did a phase 2, open-label, adaptive, randomised, controlled clinical trial on adults under 60 years old, vaccinated with a single dose of ChAdOx1-S between 8 and 12 weeks before screening, and no history of SARS-CoV-2 infection (EudraCT No. 2021-001978-37 and NCT04860739). Participants were randomly assigned (2:1) to receive BNT162b2 (0.3 mL, single intramuscular injection) or observation. The primary outcomes were 7-day reactogenicity and 14-day anti-spike IgG response, measured by immunoassays covering SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibodies functionality and cellular immune response were assessed using a pseudovirus neutralization assay and IFN-gamma immunoassay, respectively.

Findings: Between April 24 and April 30, 2021, 676 individuals were randomized (n=450 intervention group, n=226 control group) at 5 sites in Spain, and 663 (441 and 222, respectively) completed the study up to day 14 (mean age 44 [SD 9], 56·5% female). In the intervention group, geometric mean titres (GMT) of IgG-RBD increased from 71·46 BAU/mL (95% CI 59·84-85·33) at baseline to 7756·68 (7371·53; 8161·96) at day 14 (p < 0·0001). IgG against trimeric spike-protein increased from 98·4 [85.69–112.99] to 3684·87 [3429·87–3958·83]). 100% participants exhibited neutralizing antibodies 14 days after BNT162b2 administration, in comparison to 34.1% at enrolment. A 4-fold increase in cellular immune response was also observed. Reactions were predominantly mild (68·3%) or moderate (29·9%), and consisted more frequently on injection site pain (88·2%), induration (35·5%), headache (44·4%) and myalgia (43·3%). No serious adverse events were reported.

Interpretation: BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response with an acceptable and manageable reactogenicity profile.

Clinical Trial Registration Details: EudraCT No. 2021-001978-37 and NCT04860739.

Funding Information: Funded by Instituto de Salud Carlos III (ISCIII).

Declaration of Interests: CB is the Deputy General Manager of the ISCIII. JRA has received fees from Janssen, outside of the submitted work. AMB is principal investigator of clinical trials sponsored by GSK, Daiichi-Sankyo, Janssen and Farmalider, outside of the submitted work. The other authors declare no competing interests.

Ethics Approval Statement: All the participants provided written informed consent before enrolment. 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

Borobia, Alberto M and Carcas, Antonio J and Pérez Olmeda, María Teresa and Castaño, Luis and Jesús Bertrán, María and García-Pérez, Javier and Campins, Magdalena and Portolés, Antonio and Gonzalez-Perez, Maria and García Morales, María Teresa and Arana, Eunate and Aldea Novo, Marta and Díez-Fuertes, Francisco and Fuentes-Camps, Inmaculada and Ascaso, Ana and Lora, David and Imaz-Ayo, Natale and Baron-Mira, Lourdes E and Agustí, Antonia and Pérez-Ingidua, Carla and Gómez de la Cámara, Agustín and Arribas, JR and Ochando, Jordi and Alcamí Pertejo, José and Belda-Iniesta, Cristóbal and Frías, Jesús and Group, CombiVacS Study, Reactogenicity and Immunogenicity of BNT162b2 in Subjects Having Received a First Dose of ChAdOx1s: Initial Results of a Randomised, Adaptive, Phase 2 Trial (CombiVacS). Available at SSRN: https://ssrn.com/abstract=3854768 or http://dx.doi.org/10.2139/ssrn.3854768

Alberto M Borobia

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

Madrid
Spain

Antonio J Carcas

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

Madrid
Spain

María Teresa Pérez Olmeda

Carlos III Institute of Health - Laboratorio de Serología ( email )

c/ Monforte de Lemos 5
Madrid, Madrid 28029
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

Javier García-Pérez

Universidad Carlos III de Madrid - Unidad de Inmunopatología del SIDA ( email )

CL. de Madrid 126
Madrid, Madrid 28903
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

Maria Gonzalez-Perez

Carlos III Institute of Health - National Centre for Microbiology

Monforte de Lemos 5
Madrid, Madrid 28029
Spain

María Teresa García Morales

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

Madrid
Spain

Eunate Arana

Cruces University Hospital - Biocruces Bizkaia Health Research Institute ( email )

Marta Aldea Novo

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

Barcelona, 08036
Spain

Francisco Díez-Fuertes

Carlos III Institute of Health - Laboratorio de Serología

c/ Monforte de Lemos 5
Madrid, Madrid 28029
Spain

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

David Lora

University Hospital 12 de Octubre

Madrid
Spain

Natale Imaz-Ayo

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

Spain

Lourdes E Baron-Mira

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

Barcelona, 08036
Spain

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

JR Arribas

Universidad Autónoma de Madrid - Hospital Universitario La Paz. IdiPAZ ( email )

Campus Cantoblanco
C/Kelsen, 1
Madrid, Madrid 28049
Spain

Jordi Ochando

Carlos III Institute of Health - Laboratorio de Referencia en Inmunología

c/ Monforte de Lemos 5
Madrid, Madrid 28029
Spain

José Alcamí Pertejo

Carlos III Institute of Health - Unidad de Inmunopatología del SIDA ( email )

c/ Monforte de Lemos 5
Madrid, Madrid 28029
Spain

Cristóbal Belda-Iniesta (Contact Author)

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

No contact information is available for CombiVacS Study Group

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