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Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers.
EBioMedicine. 2022 Jan; 75:103805.E

Abstract

BACKGROUND

Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naïve adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness.

METHODS

We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events.

FINDINGS

Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects (p<0·05). A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with 43% (95% CI, 19-59) and 45% (95% CI, 63-18) lower neutralization, respectively, and 35% (95% CI, 3-57%) and 55% (95% CI, 33-70%) lower antibody levels, respectively. Among fully vaccinated, 6·3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection.

INTERPRETATION

Our data support administering a single-dose in pre-exposed healthy individuals as primary vaccination. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination and in face of variants that escape immunity such as Omicron. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year.

FUNDING

This work was supported by Institut de Salut Global de Barcelona (ISGlobal) internal funds, in-kind contributions from Hospital Clínic de Barcelona, the Fundació Privada Daniel Bravo Andreu, and European Institute of Innovation and Technology (EIT) Health (grant number 20877), supported by the European Institute of Innovation and Technology, a body of the European Union receiving support from the H2020 Research and Innovation Programme. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. L. I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.

Authors+Show Affiliations

ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; CIBER de Enfermedades Infecciosas, Madrid, Spain. Electronic address: gemma.moncunill@isglobal.org.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.Occupational Health Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Département Biologie, Université Claude Bernard Lyon 1, Villeurbanne, Auvergne-Rhône-Alpes, France.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Spanish Consortium for Research in Epidemiology and Public Health, Madrid, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.Immunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Department of Preventive Medicine and Epidemiology, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.Biomolecular screening and Protein Technologies Unit, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.Biomolecular screening and Protein Technologies Unit, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Spanish Consortium for Research in Epidemiology and Public Health, Madrid, Spain; Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; CIBER de Enfermedades Infecciosas, Madrid, Spain.Occupational Health Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Department of Preventive Medicine and Epidemiology, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Department of Preventive Medicine and Epidemiology, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.CIBER de Enfermedades Infecciosas, Madrid, Spain.Immunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.Immunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.Occupational Health Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; CIBER de Enfermedades Infecciosas, Madrid, Spain; Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique; International Health Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; CIBER de Enfermedades Infecciosas, Madrid, Spain. Electronic address: carlota.dobano@isglobal.org.

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

35032961

Citation

Moncunill, Gemma, et al. "Determinants of Early Antibody Responses to COVID-19 mRNA Vaccines in a Cohort of Exposed and Naïve Healthcare Workers." EBioMedicine, vol. 75, 2022, p. 103805.
Moncunill G, Aguilar R, Ribes M, et al. Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers. EBioMedicine. 2022;75:103805.
Moncunill, G., Aguilar, R., Ribes, M., Ortega, N., Rubio, R., Salmerón, G., Molina, M. J., Vidal, M., Barrios, D., Mitchell, R. A., Jiménez, A., Castellana, C., Hernández-Luis, P., Rodó, P., Méndez, S., Llupià, A., Puyol, L., Rodrigo Melero, N., Carolis, C., ... Dobaño, C. (2022). Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers. EBioMedicine, 75, 103805. https://doi.org/10.1016/j.ebiom.2021.103805
Moncunill G, et al. Determinants of Early Antibody Responses to COVID-19 mRNA Vaccines in a Cohort of Exposed and Naïve Healthcare Workers. EBioMedicine. 2022;75:103805. PubMed PMID: 35032961.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers. AU - Moncunill,Gemma, AU - Aguilar,Ruth, AU - Ribes,Marta, AU - Ortega,Natalia, AU - Rubio,Rocío, AU - Salmerón,Gemma, AU - Molina,María José, AU - Vidal,Marta, AU - Barrios,Diana, AU - Mitchell,Robert A, AU - Jiménez,Alfons, AU - Castellana,Cristina, AU - Hernández-Luis,Pablo, AU - Rodó,Pau, AU - Méndez,Susana, AU - Llupià,Anna, AU - Puyol,Laura, AU - Rodrigo Melero,Natalia, AU - Carolis,Carlo, AU - Mayor,Alfredo, AU - Izquierdo,Luis, AU - Varela,Pilar, AU - Trilla,Antoni, AU - Vilella,Anna, AU - Barroso,Sonia, AU - Angulo,Ana, AU - Engel,Pablo, AU - Tortajada,Marta, AU - García-Basteiro,Alberto L, AU - Dobaño,Carlota, Y1 - 2022/01/12/ PY - 2021/09/08/received PY - 2021/12/23/revised PY - 2021/12/23/accepted PY - 2022/1/16/pubmed PY - 2022/2/2/medline PY - 2022/1/15/entrez KW - Antibody KW - Avidity KW - COVID-19 KW - Health care workers KW - Neutralization KW - SARS-CoV-2 KW - mRNA vaccines SP - 103805 EP - 103805 JF - EBioMedicine JO - EBioMedicine VL - 75 N2 - BACKGROUND: Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naïve adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. METHODS: We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. FINDINGS: Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects (p<0·05). A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with 43% (95% CI, 19-59) and 45% (95% CI, 63-18) lower neutralization, respectively, and 35% (95% CI, 3-57%) and 55% (95% CI, 33-70%) lower antibody levels, respectively. Among fully vaccinated, 6·3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. INTERPRETATION: Our data support administering a single-dose in pre-exposed healthy individuals as primary vaccination. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination and in face of variants that escape immunity such as Omicron. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year. FUNDING: This work was supported by Institut de Salut Global de Barcelona (ISGlobal) internal funds, in-kind contributions from Hospital Clínic de Barcelona, the Fundació Privada Daniel Bravo Andreu, and European Institute of Innovation and Technology (EIT) Health (grant number 20877), supported by the European Institute of Innovation and Technology, a body of the European Union receiving support from the H2020 Research and Innovation Programme. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. L. I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. SN - 2352-3964 UR - https://www.unboundmedicine.com/medline/citation/35032961/Determinants_of_early_antibody_responses_to_COVID_19_mRNA_vaccines_in_a_cohort_of_exposed_and_naïve_healthcare_workers_ DB - PRIME DP - Unbound Medicine ER -