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Vaccine
. 2025 Sep 15:64:127750.
doi: 10.1016/j.vaccine.2025.127750. Online ahead of print. Polymyxin B as a novel mucosal adjuvant for the intranasal whole inactivated influenza vaccine
Takashi Odagiri 1 , Naoto Yoshino 1 , Yutaka Sasaki 1 , Shizuma Ishikawa 1 , Yasushi Muraki 2
Affiliations
Influenza poses a significant global health threat, and intranasal vaccines that induce mucosal immunity offer a promising alternative to traditional systemic vaccination. We previously demonstrated the mucosal adjuvanticity of polymyxin B (PMB) for several proteins; however, its potential for whole inactivated influenza virus (WIIV) remains unexplored. The present study aimed to investigate the mucosal adjuvanticity of PMB in a WIIV-immunized mouse model to develop a novel and safe intranasal influenza vaccine. Intranasal administration of WIIV combined with PMB significantly increased the number of virus-specific IgA antibody (Ab)-secreting cells at mucosal sites, thereby elevating the levels of virus-specific IgA Abs compared to the intranasal administration of WIIV alone. Upon influenza virus challenge, all mice immunized intranasally with WIIV survived. Furthermore, the mice intranasally immunized with WIIV + PMB maintained their body weight, unlike those intranasally immunized with WIIV, who experienced transient weight loss. Only 37.5 % of mice subcutaneously immunized with WIIV survived, although they exhibited higher neutralizing activity in plasma than WIIV + PMB mice. These findings demonstrate the potential of PMB as a mucosal adjuvant and indicate that substantial amounts of virus-specific IgA Abs in mucosal compartments, rather than IgG Abs in plasma, are crucial for preventing influenza virus infection. Furthermore, PMB enhanced mucosal IgA response in juvenile mice, suggesting age-independent adjuvanticity. The present study confirms the potential of PMB as an effective mucosal adjuvant when co-administered intranasally with WIIV, inducing robust mucosal IgA responses and protection against influenza challenge in both young adult and juvenile mice.
Keywords: Intranasal vaccine; Mouse model; Mucosal adjuvant; Mucosal immunity; Polymyxin B; Whole inactivated influenza virus.
. 2025 Sep 15:64:127750.
doi: 10.1016/j.vaccine.2025.127750. Online ahead of print. Polymyxin B as a novel mucosal adjuvant for the intranasal whole inactivated influenza vaccine
Takashi Odagiri 1 , Naoto Yoshino 1 , Yutaka Sasaki 1 , Shizuma Ishikawa 1 , Yasushi Muraki 2
Affiliations
- PMID: 40957307
- DOI: 10.1016/j.vaccine.2025.127750
Influenza poses a significant global health threat, and intranasal vaccines that induce mucosal immunity offer a promising alternative to traditional systemic vaccination. We previously demonstrated the mucosal adjuvanticity of polymyxin B (PMB) for several proteins; however, its potential for whole inactivated influenza virus (WIIV) remains unexplored. The present study aimed to investigate the mucosal adjuvanticity of PMB in a WIIV-immunized mouse model to develop a novel and safe intranasal influenza vaccine. Intranasal administration of WIIV combined with PMB significantly increased the number of virus-specific IgA antibody (Ab)-secreting cells at mucosal sites, thereby elevating the levels of virus-specific IgA Abs compared to the intranasal administration of WIIV alone. Upon influenza virus challenge, all mice immunized intranasally with WIIV survived. Furthermore, the mice intranasally immunized with WIIV + PMB maintained their body weight, unlike those intranasally immunized with WIIV, who experienced transient weight loss. Only 37.5 % of mice subcutaneously immunized with WIIV survived, although they exhibited higher neutralizing activity in plasma than WIIV + PMB mice. These findings demonstrate the potential of PMB as a mucosal adjuvant and indicate that substantial amounts of virus-specific IgA Abs in mucosal compartments, rather than IgG Abs in plasma, are crucial for preventing influenza virus infection. Furthermore, PMB enhanced mucosal IgA response in juvenile mice, suggesting age-independent adjuvanticity. The present study confirms the potential of PMB as an effective mucosal adjuvant when co-administered intranasally with WIIV, inducing robust mucosal IgA responses and protection against influenza challenge in both young adult and juvenile mice.
Keywords: Intranasal vaccine; Mouse model; Mucosal adjuvant; Mucosal immunity; Polymyxin B; Whole inactivated influenza virus.