TY - JOUR
T1 - Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination
T2 - Secondary analysis of the randomised CombiVacS study
AU - CombiVacS Study Group
AU - García-Pérez, Javier
AU - González-Pérez, María
AU - Castillo de la Osa, María
AU - Borobia, Alberto M.
AU - Castaño, Luis
AU - Bertrán, María Jesús
AU - Campins, Magdalena
AU - Portolés, Antonio
AU - Lora, David
AU - Bermejo, Mercedes
AU - Conde, Patricia
AU - Hernández-Gutierrez, Lourdes
AU - Carcas, Antonio
AU - Arana-Arri, Eunate
AU - Tortajada, Marta
AU - Fuentes, Inmaculada
AU - Ascaso, Ana
AU - García-Morales, María Teresa
AU - Erick de la Torre-Tarazona, Humberto
AU - Arribas, José Ramón
AU - Imaz-Ayo, Natale
AU - Mellado-Pau, Eugènia
AU - Agustí, Antonia
AU - Pérez-Ingidua, Carla
AU - Gómez de la Cámara, Agustín
AU - Ochando, Jordi
AU - Belda-Iniesta, Cristobal
AU - Frías, Jesús
AU - Alcamí, José
AU - Pérez-Olmeda, Mayte
N1 - Funding Information:
Trial conceptualisation was done by C.B.-I., J.A., M.P.-O., A.M.B., A.J.C., J.F., J.R.A. and M.C. A.J.C., J.F., and A.Ag. developed the study methods. J.A., M.P.-O., A.M.B., J.F., L.C., M.J.B., J.G.-P., M.C., A.P., M.G.-P., E.A.-A., M.T., A.As., N.I.-A., E.M., C.P.-I., J.O., M.C.-O., M.B., P.C., L.H.-G., I.F., H.E.D.T. and J.R.A. were study investigators. M.T.G.M., D.L., J.G.-P. and A.G.C. ensured data verification. J.G.-P., D.L., J.A., M.P.-O., M.T.G.M., J.O., A.M.B. and A.J.C. were responsible for the present secondary statistical analysis. C.B.-I., J.A., M.P.-O., J.G.-P., M.G.-P., A.M.B., L.C., M.C., M.J.B., A.P., J.O., J.F., and J.R.A. supervised the study. C.B.-I. was responsible for funding acquisition. J.A., M.P.O., J.O., J.G.-P. and A.M.B. wrote the original draft of this Article. All authors reviewed and edited the manuscript, and approved the manuscript for submission. All authors reviewed and approved the original draft. All authors had full access to the full data in the study and accept responsibility to submit for publication.
Funding Information:
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. VACCELERATE 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.
Publisher Copyright:
© 2022 The Authors
PY - 2022/8
Y1 - 2022/8
N2 - 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. Funding: Funded by Instituto de Salud Carlos III (ISCIII).
AB - 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. Funding: Funded by Instituto de Salud Carlos III (ISCIII).
KW - Antibodies
KW - Heterologous vaccination
KW - Neutralisation
KW - SARS-CoV-2
KW - Variants
UR - http://www.scopus.com/inward/record.url?scp=85133294716&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2022.101529
DO - 10.1016/j.eclinm.2022.101529
M3 - Article
AN - SCOPUS:85133294716
VL - 50
JO - eClinicalMedicine
JF - eClinicalMedicine
SN - 2589-5370
M1 - 101529
ER -