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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

See all articles by Emanuela Martinuzzi

Emanuela Martinuzzi

Université Côte d'Azur - Institute of Molecular and Cellular Pharmacology

Jonathan Benzaquen

Université Côte d'Azur - Department of Pulmonary Medicine and Thoracic Oncology

Olivier Guerin

Université Côte d'Azur - Autonomy Aging Rehabilitation Department

Sylvie Leroy

Université Côte d'Azur - Department of Pulmonary Medicine and Thoracic Oncology

Thomas Simon

Université Côte d'Azur - Institute of Molecular and Cellular Pharmacology

Marius Ilie

Université Côte d'Azur - Institute for Research on Cancer and Aging of Nice (IRCAN)

Véronique Hofman

Université Côte d'Azur - Institute for Research on Cancer and Aging of Nice (IRCAN)

Maryline Allegra

Université Côte d'Azur - Laboratory of Clinical and Experimental Pathology

Virginie Tanga

Université Côte d'Azur - Laboratory of Clinical and Experimental Pathology

Emeline Michel

Université Côte d'Azur - Autonomy Aging Rehabilitation Department

Jacques Boutros

Université Côte d'Azur - Department of Pulmonary Medicine and Thoracic Oncology

Charlotte Maniel

Université Côte d'Azur - Department of Pulmonary Medicine and Thoracic Oncology

Antoine Sicard

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation; Université Côte d'Azur - Clinical Research Unit Côte d’Azur

Nicolas Glaichenhaus

Université Côte d'Azur - Institute of Molecular and Cellular Pharmacology

Cecil Czerkinsky

Université Côte d'Azur - Institute of Molecular and Cellular Pharmacology

Philippe Blancou

Université Côte d'Azur - Institute of Molecular and Cellular Pharmacology

Paul Hofman

Université Côte d'Azur - Institute for Research on Cancer and Aging of Nice (IRCAN)

Charles-Hugo Marquette

Université Côte d'Azur - Department of Pulmonary Medicine and Thoracic Oncology

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

Martinuzzi, Emanuela and Benzaquen, Jonathan and Guerin, Olivier and Leroy, Sylvie and Simon, Thomas and Ilie, Marius and Hofman, Véronique and Allegra, Maryline and Tanga, Virginie and Michel, Emeline and Boutros, Jacques and Maniel, Charlotte and Sicard, Antoine and Glaichenhaus, Nicolas and Czerkinsky, Cecil and Blancou, Philippe and Hofman, Paul and Marquette, Charles-Hugo, A Single Dose of COVID-19 mRNA Vaccine Induces Airway Immunity in COVID-19 Convalescent Patients. Available at SSRN: https://ssrn.com/abstract=3984113 or http://dx.doi.org/10.2139/ssrn.3984113

Emanuela Martinuzzi

Université Côte d'Azur - Institute of Molecular and Cellular Pharmacology ( email )

Valbonne
France

Jonathan Benzaquen

Université Côte d'Azur - Department of Pulmonary Medicine and Thoracic Oncology ( email )

Nice
France

Olivier Guerin

Université Côte d'Azur - Autonomy Aging Rehabilitation Department ( email )

Nice
France

Sylvie Leroy

Université Côte d'Azur - Department of Pulmonary Medicine and Thoracic Oncology ( email )

Nice
France

Thomas Simon

Université Côte d'Azur - Institute of Molecular and Cellular Pharmacology ( email )

Valbonne
France

Marius Ilie

Université Côte d'Azur - Institute for Research on Cancer and Aging of Nice (IRCAN) ( email )

France

Véronique Hofman

Université Côte d'Azur - Institute for Research on Cancer and Aging of Nice (IRCAN) ( email )

France

Maryline Allegra

Université Côte d'Azur - Laboratory of Clinical and Experimental Pathology ( email )

Centre Nice
France

Virginie Tanga

Université Côte d'Azur - Laboratory of Clinical and Experimental Pathology ( email )

Centre Nice
France

Emeline Michel

Université Côte d'Azur - Autonomy Aging Rehabilitation Department ( email )

Nice
France

Jacques Boutros

Université Côte d'Azur - Department of Pulmonary Medicine and Thoracic Oncology ( email )

Nice
France

Charlotte Maniel

Université Côte d'Azur - Department of Pulmonary Medicine and Thoracic Oncology ( email )

Nice
France

Antoine Sicard

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation ( email )

Nice
France

Université Côte d'Azur - Clinical Research Unit Côte d’Azur ( email )

Nice
France

Nicolas Glaichenhaus

Université Côte d'Azur - Institute of Molecular and Cellular Pharmacology ( email )

Valbonne
France

Cecil Czerkinsky

Université Côte d'Azur - Institute of Molecular and Cellular Pharmacology ( email )

Valbonne
France

Philippe Blancou

Université Côte d'Azur - Institute of Molecular and Cellular Pharmacology ( email )

Valbonne
France

Paul Hofman

Université Côte d'Azur - Institute for Research on Cancer and Aging of Nice (IRCAN) ( email )

France

Charles-Hugo Marquette (Contact Author)

Université Côte d'Azur - Department of Pulmonary Medicine and Thoracic Oncology ( email )

Nice
France