1. Academic Validation
  2. Suitability of Polymyxin B as a Mucosal Adjuvant for Intranasal Influenza and COVID-19 Vaccines

Suitability of Polymyxin B as a Mucosal Adjuvant for Intranasal Influenza and COVID-19 Vaccines

  • Vaccines (Basel). 2023 Nov 18;11(11):1727. doi: 10.3390/vaccines11111727.
Naoto Yoshino 1 Takuya Yokoyama 2 3 Hironori Sakai 4 Ikumi Sugiyama 5 Takashi Odagiri 1 Masahiro Kimura 1 Wataru Hojo 4 Tomoyuki Saino 2 Yasushi Muraki 1
Affiliations

Affiliations

  • 1 Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba 028-3694, Iwate, Japan.
  • 2 Department of Anatomy (Cell Biology), Iwate Medical University, 1-1-1 Idaidori, Yahaba 028-3694, Iwate, Japan.
  • 3 Laboratory of Veterinary Anatomy and Cell Biology, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka 020-8550, Iwate, Japan.
  • 4 R&D, Cellspect Co., Ltd., 2-4-23 Kitaiioka, Morioka 020-0857, Iwate, Japan.
  • 5 Division of Advanced Pharmaceutics, Department of Clinical Pharmaceutical Science, School of Pharmacy, Iwate Medical University, 1-1-1 Idaidori, Yahaba 028-3694, Iwate, Japan.
Abstract

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.

Keywords

S protein; S1 subunit; SARS-CoV-2; hemagglutinin; influenza A virus; mucosal adjuvant; polymyxin B.

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