Suitability of Polymyxin B as a Mucosal Adjuvant for Intranasal Influenza and COVID-19 Vaccines
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Updated: Jun 24, 2026

Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Naoto Yoshino1, Takuya Yokoyama2,3, Hironori Sakai4
1Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, 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.
Insights
Polymyxin B enhances mucosal immunity against viral infections. This antibiotic boosts IgA and IgG antibody production for intranasal vaccines, showing potential for preventing infections like SARS-CoV-2.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infections highlight insufficient mucosal IgA from mRNA vaccines.
- Polymyxin B (PMB) is known to enhance mucosal immunity for ovalbumin (OVA), but its adjuvanticity for other antigens is unexplored.
Purpose of the Study:
- To investigate the mucosal adjuvanticity of Polymyxin B (PMB) for influenza A virus hemagglutinin (HA) and SARS-CoV-2 spike (S) proteins.
- To evaluate the potential of PMB as an intranasal vaccine adjuvant for inducing mucosal immunity.
Main Methods:
- BALB/c mice were immunized intranasally or subcutaneously with HA or SARS-CoV-2 S proteins, alone or with PMB.
- Antigen-specific IgA and IgG antibody levels in mucosal secretions and plasma were quantified.
- The diameter of PMB-virus antigen complexes was analyzed for its role in mucosal immunity induction.
Main Results:
- PMB significantly increased antigen-specific IgA in mucosal secretions and IgG in plasma for both HA and S proteins.
- The size of the PMB-virus antigen complex was found to be critical for inducing mucosal immunity.
- No adverse effects were observed on the nasal mucosa or olfactory bulb.
Conclusions:
- Polymyxin B demonstrates mucosal adjuvanticity for viral antigens, enhancing both IgA and IgG antibody responses.
- PMB shows promise as a safe intranasal adjuvant for inducing protective mucosal immunity against transmissible infections.
- Optimizing PMB-virus antigen complex size is key for effective intranasal vaccine development.
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