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Humoral Responses Against Variants of Concern by COVID-19 mRNA Vaccines in Immunocompromised Patients

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Key Points

Question  Are there differences in the magnitude and durability of neutralizing antibody (nAb) responses against SARS-CoV-2 variants of concern (VOCs) according to the mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) vaccines?

Findings  In this comparative effectiveness study of 637 immunocompromised patients and 204 healthy control participants who received 2 doses of messenger RNA COVID-19 vaccines, nAb responses against the Beta and Delta variants were short lived (3 to 7 months) compared with original, nonvariant SARS-CoV-2 and other variants. Higher nAb titers and longer durability of humoral responses were associated with vaccination with the mRNA-1273 vaccine.

Meaning  The faster disappearance of the nAb responses in certain groups of immunocompromised patients suggests that boosting vaccine strategies need to be personalized to the underlying disease.


Importance  There are limited comparative data on the durability of neutralizing antibody (nAb) responses elicited by messenger RNA (mRNA) vaccines against the SARS-CoV-2 variants of concern (VOCs) in immunocompromised patients and healthy controls.

Objective  To assess the humoral responses after vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines.

Design, Setting, and Participants  In this prospective, longitudinal monocentric comparative effectiveness study conducted at the Lausanne University Hospital, binding IgG anti-spike antibody and nAb levels were measured at 1 week, 1 month, 3 months, and 6 months after vaccination with mRNA-1273 (24.6% of participants) or BNT162b2 (75.3% of participants).

Interventions  All participants received 2 doses of either mRNA-1273 or BNT162b2 vaccines 4 to 6 weeks apart.

Main Outcomes and Measures  The primary outcome of the study was the persistence of nAb responses against the original, nonvariant SARS-CoV-2 (2019-nCoV) and different VOCs at 6 months after vaccination. Key secondary outcomes were associations of the type of mRNA vaccine, the underlying disease, and the treatment with the response to vaccination.

Results  Among the 841 participants enrolled between January 14 and August 8, 2021, the patient population comprised 637 participants (mean [SD] age, 61.8 [13.7] years; 386 [60.6%] female), and the healthy control population comprised 204 participants (mean [SD] age, 45.9 [12.0] years; 144 [70.6%] female). There were 399 patients with solid cancers, 101 with hematologic cancers, 38 with solid organ transplants, 99 with autoimmune diseases, and 204 healthy controls. More than 15 000 nAb determinations were performed against the original, nonvariant 2019-nCoV and the Alpha, Beta, Gamma, and Delta variants. The proportions of nAbs and their titers decreased in all study groups at 6 months after vaccination, with the greatest decreases for the Beta and Delta variants. For Beta, the proportion decreased to a median (SE) of 39.2% (5.5%) in those with hematologic cancers, 44.8% (2.7%) in those with solid cancers, 23.1% (8.3%) in those with solid organ transplants, and 22.7% (4.8%) in those with autoimmune diseases compared with 52.1% (4.2%) in healthy controls. For Delta, the proportions decreased to 41.8% (5.6%) in participants with hematologic cancer, 51.9% (2.7%) in those with solid cancers, 26.9% (8.7%) in those with solid organ transplants, and 30.7% (5.3%) in those with autoimmune diseases compared with 56.9% (4.1%) healthy controls. Neutralizing antibody titers decreased 3.5- to 5-fold between month 1 and month 6, and the estimated duration of response was greater and more durable among those participants vaccinated with mRNA-1273. In participants with solid cancers, the estimated duration of nAbs against the Beta variant was 221 days with mRNA-1273 and 146 days with BNT162b2, and against the Delta variant, it was 226 days with mRNA-1273 and 161 with BNT162b2. The estimated duration of nAbs in participants with hematologic cancers was 113 and 127 days against Beta and Delta variants, respectively.

Conclusions and Relevance  This comparative effectiveness study suggests that approximately half of patients with hematologic cancers and solid cancers, about 70% of patients with solid organ transplants or autoimmune diseases, and 40% of healthy controls have lost nAbs against the circulating VOCs at 6 months after vaccination. These findings may be helpful for developing the best boosting vaccination schedule especially in immunocompromised patients.

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Article Information

Accepted for Publication: February 7, 2022.

Published Online: March 10, 2022. doi:10.1001/jamaoncol.2022.0446

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Obeid M et al. JAMA Oncology.

Corresponding Author: Giuseppe Pantaleo, MD, Service of Immunology and Allergy, Departments of Medicine and Laboratory Medicine and Pathology, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland (

Author Contributions: Drs Obeid and Pantaleo had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Obeid, Suffiotti, and Pellaton contributed equally to the work.

Concept and design: Obeid, Cairoli, Salvadé, Coutechier, Trono, Peters, Pantaleo.

Acquisition, analysis, or interpretation of data: Obeid, Suffiotti, Pellaton, Bouchaab, Cairoli, Stevenel, Hottinger, Pythoud, Molinari, Ribi, Gottardo, Fenwick, Pascual, Duchosal, Peters, Pantaleo.

Drafting of the manuscript: Obeid, Cairoli, Salvadé, Stevenel, Pythoud, Gottardo, Peters, Pantaleo.

Critical revision of the manuscript for important intellectual content: Obeid, Suffiotti, Pellaton, Bouchaab, Stevenel, Hottinger, Coutechier, Molinari, Trono, Ribi, Gottardo, Fenwick, Pascual, Duchosal, Pantaleo.

Statistical analysis: Obeid, Suffiotti, Pellaton, Gottardo, Pascual, Peters.

Obtained funding: Fenwick, Peters, Pantaleo.

Administrative, technical, or material support: Obeid, Pellaton, Bouchaab, Cairoli, Salvadé, Stevenel, Hottinger, Pythoud, Coutechier, Molinari, Fenwick, Pascual, Duchosal, Peters.

Supervision: Obeid, Pellaton, Stevenel, Hottinger, Trono, Ribi, Gottardo, Peters, Pantaleo.

Conflict of Interest Disclosures: Dr Gottardo reported receiving personal fees from Takeda Consulting, and owning stocks from BioNTech, Ozette, and Modulus Therapeutics outside the submitted work. Dr Fenwick reported having a patent pending (application No. EP20205298.1) for a neutralization assay used in this study. Dr Peters reported receiving personal fees (all to her institution) from advisory boards of Amgen, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, Foundation Medicine, Janssen, Merck Sharp & Dohme, Merck Serono, Novartis, PharmaMar, Phosplatin Therapeutics, Pfizer, Regeneron, Roche, Sanofi, Seattle Genetics, and Takeda outside the submitted work. Dr Pantaleo reported having a patent pending (application No. EP20205298.1) for a neutralization assay used in this study. No other disclosures were reported.

Funding/Support: Dr Obeid received a grant from the Leenaards Foundation. Dr Pantaleo received a grant (No. 101005077) from the Corona Accelerated R&D in Europe project funded by the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 101005077. The JU receives support from the European Union’s Horizon 2020 research and innovation program, the European Federation of Pharmaceutical Industries Associations, the Bill and Melinda Gates Foundation, Global Health Drug Discovery Institute, and the University of Dundee and from Lausanne University Hospital, the Swiss Vaccine Research Institute, and Swiss National Science Foundation grants. The research is partially supported by the CoVICIS project (grant No. 101046041) funded by the European Union Horizon Europe Program.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: The authors thank the participants who volunteered for this study and the Vaccine and Immunology Center and the clinical diagnosis platform of the Service of Immunology and Allergy, Departments of Medicine and Laboratory Medicine and Pathology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland, for enrollment of the participants and collection and processing of samples.

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