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

Kentaro Muranishi; Mao Kinoshita; Keita Inoue; Junya Ohara; Toshihito Mihara; Kazuki Sudo; Ken J Ishii; Teiji Sawa; Hiroyasu Ishikura

doi:10.3390/vaccines12010005

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

Vaccines (Basel). 2023 Dec 20;12(1):5. doi: 10.3390/vaccines12010005.

Authors

Kentaro Muranishi¹, Mao Kinoshita², Keita Inoue², Junya Ohara², Toshihito Mihara², Kazuki Sudo², Ken J Ishii³, Teiji Sawa², Hiroyasu Ishikura¹

Affiliations

¹ Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University, Fukuoka 814-0133, Japan.
² Department of Anesthesiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
³ Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.

Abstract

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.

Keywords: CpG-deoxyoligonucleotide; SARS-CoV-2; intranasal administration; mucosal immunity; recombinant protein.

Grants and funding

This study was supported by the Japan Society for the Promotion of Science and a Grant-in-Aid for Scientific Research (KAKENHI) to Mao Kinoshita (Grant No. 21K16593 and 18K16521) and Teiji Sawa (Grant No. 22H03176 and 18K19590) from the Ministry of Education, Culture, Sports, Science and Technology, Japan to T.S. and M.K. The funding agency did not play any role in the study design, collection, analysis, and interpretation of the data, the writing of the report, or the decision to submit the article for publication.