Antibody Response Following the Intranasal Administration of SARS-CoV-2 Spike Protein-CpG Oligonucleotide Vaccine

The new coronavirus infection causes severe respiratory failure following respiratory tract infection with severe acute respiratory syndrome-related coronavirus (SARS-CoV-2). All currently approved vaccines are administered intramuscularly; however, intranasal administration enhances mucosal immunit...

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Main Authors: Kentaro Muranishi, Mao Kinoshita, Keita Inoue, Junya Ohara, Toshihito Mihara, Kazuki Sudo, Ken J. Ishii, Teiji Sawa, Hiroyasu Ishikura
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/12/1/5
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author Kentaro Muranishi
Mao Kinoshita
Keita Inoue
Junya Ohara
Toshihito Mihara
Kazuki Sudo
Ken J. Ishii
Teiji Sawa
Hiroyasu Ishikura
author_facet Kentaro Muranishi
Mao Kinoshita
Keita Inoue
Junya Ohara
Toshihito Mihara
Kazuki Sudo
Ken J. Ishii
Teiji Sawa
Hiroyasu Ishikura
author_sort Kentaro Muranishi
collection DOAJ
description The new coronavirus infection causes severe respiratory failure following respiratory tract infection with severe acute respiratory syndrome-related coronavirus (SARS-CoV-2). All currently approved vaccines are administered intramuscularly; however, intranasal administration enhances mucosal immunity, facilitating the production of a less invasive vaccine with fewer adverse events. Herein, a recombinant vaccine combining the SARS-CoV-2 spike protein receptor-binding domain (RBD), or S1 protein, with CpG-deoxyoligonucleotide (ODN) or aluminum hydroxide (alum) adjuvants was administered intranasally or subcutaneously to mice. Serum-specific IgG titers, IgA titers in the alveolar lavage fluid, and neutralizing antibody titers were analyzed. The nasal administration of RBD protein did not increase serum IgG or IgA titers in the alveolar lavage fluid. However, a significant increase in serum IgG was observed in the intranasal group administered with S1 protein with CpG-ODN and the subcutaneous group administered with S1 protein with alum. The IgA and IgG levels increased significantly in the alveolar lavage fluid only after the intranasal administration of the S1 protein with CpG-ODN. The neutralizing antibody titers in serum and bronchoalveolar lavage were significantly higher in the intranasal S1-CpG group than in every other group. Hence, the nasal administration of the S1 protein vaccine with CpG adjuvant might represent an effective vaccine candidate.
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spelling doaj.art-c426742842ab44f89af99efa0178e59d2024-01-29T14:25:07ZengMDPI AGVaccines2076-393X2023-12-01121510.3390/vaccines12010005Antibody Response Following the Intranasal Administration of SARS-CoV-2 Spike Protein-CpG Oligonucleotide VaccineKentaro Muranishi0Mao Kinoshita1Keita Inoue2Junya Ohara3Toshihito Mihara4Kazuki Sudo5Ken J. Ishii6Teiji Sawa7Hiroyasu Ishikura8Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University, Fukuoka 814-0133, JapanDepartment of Anesthesiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, JapanDepartment of Anesthesiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, JapanDepartment of Anesthesiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, JapanDepartment of Anesthesiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, JapanDepartment of Anesthesiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, JapanDivision of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, JapanDepartment of Anesthesiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, JapanDepartment of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University, Fukuoka 814-0133, JapanThe new coronavirus infection causes severe respiratory failure following respiratory tract infection with severe acute respiratory syndrome-related coronavirus (SARS-CoV-2). All currently approved vaccines are administered intramuscularly; however, intranasal administration enhances mucosal immunity, facilitating the production of a less invasive vaccine with fewer adverse events. Herein, a recombinant vaccine combining the SARS-CoV-2 spike protein receptor-binding domain (RBD), or S1 protein, with CpG-deoxyoligonucleotide (ODN) or aluminum hydroxide (alum) adjuvants was administered intranasally or subcutaneously to mice. Serum-specific IgG titers, IgA titers in the alveolar lavage fluid, and neutralizing antibody titers were analyzed. The nasal administration of RBD protein did not increase serum IgG or IgA titers in the alveolar lavage fluid. However, a significant increase in serum IgG was observed in the intranasal group administered with S1 protein with CpG-ODN and the subcutaneous group administered with S1 protein with alum. The IgA and IgG levels increased significantly in the alveolar lavage fluid only after the intranasal administration of the S1 protein with CpG-ODN. The neutralizing antibody titers in serum and bronchoalveolar lavage were significantly higher in the intranasal S1-CpG group than in every other group. Hence, the nasal administration of the S1 protein vaccine with CpG adjuvant might represent an effective vaccine candidate.https://www.mdpi.com/2076-393X/12/1/5SARS-CoV-2intranasal administrationmucosal immunityrecombinant proteinCpG-deoxyoligonucleotide
spellingShingle Kentaro Muranishi
Mao Kinoshita
Keita Inoue
Junya Ohara
Toshihito Mihara
Kazuki Sudo
Ken J. Ishii
Teiji Sawa
Hiroyasu Ishikura
Antibody Response Following the Intranasal Administration of SARS-CoV-2 Spike Protein-CpG Oligonucleotide Vaccine
Vaccines
SARS-CoV-2
intranasal administration
mucosal immunity
recombinant protein
CpG-deoxyoligonucleotide
title Antibody Response Following the Intranasal Administration of SARS-CoV-2 Spike Protein-CpG Oligonucleotide Vaccine
title_full Antibody Response Following the Intranasal Administration of SARS-CoV-2 Spike Protein-CpG Oligonucleotide Vaccine
title_fullStr Antibody Response Following the Intranasal Administration of SARS-CoV-2 Spike Protein-CpG Oligonucleotide Vaccine
title_full_unstemmed Antibody Response Following the Intranasal Administration of SARS-CoV-2 Spike Protein-CpG Oligonucleotide Vaccine
title_short Antibody Response Following the Intranasal Administration of SARS-CoV-2 Spike Protein-CpG Oligonucleotide Vaccine
title_sort antibody response following the intranasal administration of sars cov 2 spike protein cpg oligonucleotide vaccine
topic SARS-CoV-2
intranasal administration
mucosal immunity
recombinant protein
CpG-deoxyoligonucleotide
url https://www.mdpi.com/2076-393X/12/1/5
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