| Autor: |
Uchiyama H; Department of Bacteriology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.; Department of Vascular Surgery, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan., Kudo T; Department of Vascular Surgery, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan., Yamaguchi T; Department of Bacteriology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan., Obana N; Tsukuba Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.; Microbiology Research Center for Sustainability, University of Tsukuba, Tsukuba, Japan., Watanabe K; Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan., Abe K; Department of Bacteriology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.; Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan., Miyazaki H; Department of Oculoplastic, Orbital and Lacrimal Surgery, Aichi Medical University, Nagakute, Japan.; Department of Oral and Maxillofacial Surgery, Division of Oral Health Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan., Toyofuku M; Microbiology Research Center for Sustainability, University of Tsukuba, Tsukuba, Japan., Nomura N; Microbiology Research Center for Sustainability, University of Tsukuba, Tsukuba, Japan., Akeda Y; Department of Bacteriology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan., Nakao R; Department of Bacteriology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan. |
| Abstrakt: |
There is a growing interest in development of novel vaccines against respiratory tract infections, due to COVID-19 pandemic. Here, we examined mucosal adjuvanticity and the mucosal booster effect of membrane vesicles (MVs) of a novel probiotic E. coli derivative lacking both flagella and potentially carcinogenic colibactin (Δ flhD Δ clbP ). Δ flhD Δ clbP -derived MVs showed rather strong mucosal adjuvanticity as compared to those of a single flagellar mutant strain (Δ flhD -MVs). In addition, glycoengineered Δ flhD Δ clbP -MVs displaying serotype-14 pneumococcal capsular polysaccharide (CPS14 + MVs) were well-characterized based on biological and physicochemical parameters. Subcutaneous (SC) and intranasal (IN) booster effects of CPS14 + MVs on systemic and mucosal immunity were evaluated in mice that have already been subcutaneously prime-immunized with the same MVs. With a two-dose regimen, an IN boost (SC-IN) elicited stronger IgA responses than homologous prime-boost immunization (SC-SC). With a three-dose regimen, serum IgG levels were comparable among all tested regimens. Homologous immunization (SC-SC-SC) elicited the highest IgM responses among all regimens tested, whereas SC-SC-SC failed to elicit IgA responses in blood and saliva. Furthermore, serum IgA and salivary SIgA levels were increased with an increased number of IN doses administrated. Notably, SC-IN-IN induced not only robust IgG response, but also the highest IgA response in both serum and saliva among the groups. The present findings suggest the potential of a heterologous three-dose administration for building both systemic and mucosal immunity, e.g . an SC-IN-IN vaccine regimen could be beneficial. Another important observation was abundant packaging of colibactin in MVs, suggesting increased applicability of Δ flhD Δ clbP -MVs in the context of vaccine safety. |
