Suitability of Polymyxin B as a Mucosal Adjuvant for Intranasal Influenza and COVID-19 Vaccines
Naoto Yoshino,
Takuya Yokoyama,
Hironori Sakai,
Ikumi Sugiyama,
Takashi Odagiri,
Masahiro Kimura,
Wataru Hojo,
Tomoyuki Saino,
Yasushi Muraki
Affiliations
Naoto Yoshino
Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba 028-3694, Iwate, Japan
Takuya Yokoyama
Department of Anatomy (Cell Biology), Iwate Medical University, 1-1-1 Idaidori, Yahaba 028-3694, Iwate, Japan
Hironori Sakai
R&D, Cellspect Co., Ltd., 2-4-23 Kitaiioka, Morioka 020-0857, Iwate, Japan
Ikumi Sugiyama
Division of Advanced Pharmaceutics, Department of Clinical Pharmaceutical Science, School of Pharmacy, Iwate Medical University, 1-1-1 Idaidori, Yahaba 028-3694, Iwate, Japan
Takashi Odagiri
Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba 028-3694, Iwate, Japan
Masahiro Kimura
Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba 028-3694, Iwate, Japan
Wataru Hojo
R&D, Cellspect Co., Ltd., 2-4-23 Kitaiioka, Morioka 020-0857, Iwate, Japan
Tomoyuki Saino
Department of Anatomy (Cell Biology), Iwate Medical University, 1-1-1 Idaidori, Yahaba 028-3694, Iwate, Japan
Yasushi Muraki
Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba 028-3694, Iwate, Japan
Polymyxin B (PMB) is an antibiotic that exhibits mucosal adjuvanticity for ovalbumin (OVA), which enhances the immune response in the mucosal compartments of mice. Frequent breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants indicate that the IgA antibody levels elicited by the mRNA vaccines in the mucosal tissues were insufficient for the prophylaxis of this infection. It remains unknown whether PMB exhibits mucosal adjuvanticity for antigens other than OVA. This study investigated the adjuvanticity of PMB for the virus proteins, hemagglutinin (HA) of influenza A virus, and the S1 subunit and S protein of SARS-CoV-2. BALB/c mice immunized either intranasally or subcutaneously with these antigens alone or in combination with PMB were examined, and the antigen-specific antibodies were quantified. PMB substantially increased the production of antigen-specific IgA antibodies in mucosal secretions and IgG antibodies in plasma, indicating its adjuvanticity for both HA and S proteins. This study also revealed that the PMB-virus antigen complex diameter is crucial for the induction of mucosal immunity. No detrimental effects were observed on the nasal mucosa or olfactory bulb. These findings highlight the potential of PMB as a safe candidate for intranasal vaccination to induce mucosal IgA antibodies for prophylaxis against mucosally transmitted infections.
