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A Single Dose of COVID-19 mRNA Vaccine Induces Airway Immunity in COVID-19 Convalescent Patients
21 Pages Posted: 13 Dec 2021
More...Abstract
Background: Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and hence virus shedding. Preclinical and clinical studies have shown that a parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior infection or mucosal immunization compared to two injections of a parenteral vaccine. We investigated whether this was also the case for a COVID-19 mRNA vaccine.
Methods: Twenty-three COVID-19 convalescent patients and 20 SARS-CoV-2-naive subjects were vaccinated with respectively one and two doses of the Pfizer-BioNTech COVID-19 RNA vaccine. Nasal Epithelial Lining Fluid (NELF) and plasma were collected before and after vaccination and assessed for Immunoglobulin (Ig)G and IgA to Spike and for their ability to inhibit the binding of Spike to its ACE-2 receptor. Blood was analyzed one week after vaccination for the number of Spike-specific Antibody Secreting Cells (ASCs) with a mucosal tropism.
Findings: In COVID-19 convalescent patients, a single dose of vaccine amplified pre-existing Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains including delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2-naive subjects after two vaccine doses.
Interpretation: This study showed that a parenteral booster injection of a COVID-19 RNA vaccine promoted stronger mucosal immune responses in COVID-19 convalescent patients compared to SARS-CoV-2 naive subjects who had received a first vaccine dose. These findings strongly lend support to the development of mucosal COVID vaccine formulations to induce airway immunity and thereby to limit infection and viral carriage and transmission when combined with existing parenteral vaccines.
Clinical Trial Registration Details: The study was registered on ClinicalTrial.gov (NCT04418206).
Funding Information: Research reported in this publication was supported by grants from the Ministère de l’Enseignement Supérieur et de la Recherche, the Conseil Départemental des Alpes Maritimes, the Métropole Nice Côte d’Azur. Special thanks to E. Faidhi, N. Fridlyand, A. Rauscher, E. Maris, the Lauro family and to the many private donators for their generous contribution.
Declaration of Interests: The authors declare no competing interests.
Ethics Approval Statement: All subjects signed an informed consent to participate in this work. The study protocol conformed to the ethical guidelines of the declaration of Helsinki. The promoter of the study was the Nice University Hospital. The study was reviewed and approved by the national ethics committee (CPP Sud Méditerranée V; CNRIPH registration # 20.04.14.35208; approval number 2020-A01050-39).
Keywords: mucosal immunity, secretory antibodies, SARS-CoV-2, COVID-19 mRNA vaccine
Suggested Citation: Suggested Citation