---
title: "Mucosal prime–systemic boost with a glycoengineered membrane vesicle vaccine protects mice from pn"
id: "pubmed-42759251"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42759251"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42759251/"
doi: "10.1016/j.vaccine.2026.129142"
published_at: "2026-10-24T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Mucosal prime–systemic boost with a glycoengineered membrane vesicle vaccine protects mice from pn
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42759251
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42759251/)
- **DOI:** [10.1016/j.vaccine.2026.129142](https://doi.org/10.1016%2Fj.vaccine.2026.129142)
- **Published At:** 2026-10-24T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Investigators evaluated all eight possible three-dose combinations of intranasal (IN) and subcutaneous (SC) administration using a **glycoengineered membrane vesicle vaccine** displaying pneumococcal capsular polysaccharide. - The vaccine platform, derived from probiotic Escherichia coli and described as self-adjuvanting, induced robust humoral responses across routes. - Serum IgG responses were elicited by every regimen tested; systemic antibody induction did not depend on route. - Strong mucosal **SIgA** responses and improved nasal clearance of pneumococci were observed only after IN-IN-IN, IN-IN-SC, and SC-IN-IN schedules. - The heterologous IN-IN-SC sequence produced a balance of mucosal and systemic immunity and showed the highest measured **opsonophagocytic activity** among regimens. - Enhanced pneumococcal clearance at the nasal mucosa correlated with mucosal SIgA induction in the effective regimens. - All findings were generated in a mouse model; the source did not report human data, dosing specifics, sample sizes, or detailed safety endpoints. - Authors concluded that optimization of administration route is a practical strategy to maximize efficacy of glycoengineered membrane vesicle vaccines against **pneumococci**.
## Clinical Analysis & Structured Key Points
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Epub 2026 Sep 18. # A mucosal prime-systemic boost strategy using a glycoengineered bacterial membrane vesicle vaccine elicits protective mucosal immunity against pneumococci in mice [Ryoma Nakao](https://pubmed.ncbi.nlm.nih.gov/?term=Nakao+R&cauthor_id=42759251)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#full-view-affiliation-1 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. Electronic address: nakao.ry@jihs.go.jp."), [Hiroki Uchiyama](https://pubmed.ncbi.nlm.nih.gov/?term=Uchiyama+H&cauthor_id=42759251)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#full-view-affiliation-2 "Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan."), [Takehiro Yamaguchi](https://pubmed.ncbi.nlm.nih.gov/?term=Yamaguchi+T&cauthor_id=42759251)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#full-view-affiliation-3 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan."), [Kimihiro Abe](https://pubmed.ncbi.nlm.nih.gov/?term=Abe+K&cauthor_id=42759251)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#full-view-affiliation-4 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Research Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan."), [Aoi Takahashi](https://pubmed.ncbi.nlm.nih.gov/?term=Takahashi+A&cauthor_id=42759251)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#full-view-affiliation-5 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Research and Education Center for Prevention of Global Infectious Diseases of Animals, Tokyo University of Agriculture and Technology, Tokyo, Japan."), [Manami Kimijima](https://pubmed.ncbi.nlm.nih.gov/?term=Kimijima+M&cauthor_id=42759251)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#full-view-affiliation-3 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan."), [Eisuke Kuroda](https://pubmed.ncbi.nlm.nih.gov/?term=Kuroda+E&cauthor_id=42759251)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#full-view-affiliation-6 "Graduate School of Medicine, Nagoya University, Aichi, Japan."), [Shigeto Hamaguchi](https://pubmed.ncbi.nlm.nih.gov/?term=Hamaguchi+S&cauthor_id=42759251)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#full-view-affiliation-7 "Osaka Institute of Public Health, Osaka, Japan."), [Toshifumi Kudo](https://pubmed.ncbi.nlm.nih.gov/?term=Kudo+T&cauthor_id=42759251)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#full-view-affiliation-8 "Tsuchiura Kyodo General Hospital, Ibaraki, Japan."), [Yukihiro Akeda](https://pubmed.ncbi.nlm.nih.gov/?term=Akeda+Y&cauthor_id=42759251)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#full-view-affiliation-9 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Graduate School of Medicine, The University of Osaka, Osaka, Japan; Research Institute for Microbial Diseases, The University of Osaka, Osaka, Japan; Chulalongkorn University, Bangkok, Thailand.") Affiliations Expand ### Affiliations * 1 Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. Electronic address: nakao.ry@jihs.go.jp. * 2 Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan. * 3 Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. * 4 Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Research Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. * 5 Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Research and Education Center for Prevention of Global Infectious Diseases of Animals, Tokyo University of Agriculture and Technology, Tokyo, Japan. * 6 Graduate School of Medicine, Nagoya University, Aichi, Japan. * 7 Osaka Institute of Public Health, Osaka, Japan. * 8 Tsuchiura Kyodo General Hospital, Ibaraki, Japan. * 9 Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Graduate School of Medicine, The University of Osaka, Osaka, Japan; Research Institute for Microbial Diseases, The University of Osaka, Osaka, Japan; Chulalongkorn University, Bangkok, Thailand. * PMID: **42759251** * DOI: [ 10.1016/j.vaccine.2026.129142 ](https://doi.org/10.1016/j.vaccine.2026.129142) Free article Item in Clipboard # A mucosal prime-systemic boost strategy using a glycoengineered bacterial membrane vesicle vaccine elicits protective mucosal immunity against pneumococci in mice Ryoma Nakao et al. Vaccine. 2026. Free article Show details Display options Display options Format Abstract PubMed PMID Vaccine Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Vaccine%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Vaccine%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42759251/) . 2026 Oct 24:92:129142. doi: 10.1016/j.vaccine.2026.129142. Epub 2026 Sep 18. ### Authors [Ryoma Nakao](https://pubmed.ncbi.nlm.nih.gov/?term=Nakao+R&cauthor_id=42759251)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#short-view-affiliation-1 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. Electronic address: nakao.ry@jihs.go.jp."), [Hiroki Uchiyama](https://pubmed.ncbi.nlm.nih.gov/?term=Uchiyama+H&cauthor_id=42759251)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#short-view-affiliation-2 "Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan."), [Takehiro Yamaguchi](https://pubmed.ncbi.nlm.nih.gov/?term=Yamaguchi+T&cauthor_id=42759251)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#short-view-affiliation-3 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan."), [Kimihiro Abe](https://pubmed.ncbi.nlm.nih.gov/?term=Abe+K&cauthor_id=42759251)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#short-view-affiliation-4 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Research Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan."), [Aoi Takahashi](https://pubmed.ncbi.nlm.nih.gov/?term=Takahashi+A&cauthor_id=42759251)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#short-view-affiliation-5 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Research and Education Center for Prevention of Global Infectious Diseases of Animals, Tokyo University of Agriculture and Technology, Tokyo, Japan."), [Manami Kimijima](https://pubmed.ncbi.nlm.nih.gov/?term=Kimijima+M&cauthor_id=42759251)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#short-view-affiliation-3 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan."), [Eisuke Kuroda](https://pubmed.ncbi.nlm.nih.gov/?term=Kuroda+E&cauthor_id=42759251)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#short-view-affiliation-6 "Graduate School of Medicine, Nagoya University, Aichi, Japan."), [Shigeto Hamaguchi](https://pubmed.ncbi.nlm.nih.gov/?term=Hamaguchi+S&cauthor_id=42759251)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#short-view-affiliation-7 "Osaka Institute of Public Health, Osaka, Japan."), [Toshifumi Kudo](https://pubmed.ncbi.nlm.nih.gov/?term=Kudo+T&cauthor_id=42759251)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#short-view-affiliation-8 "Tsuchiura Kyodo General Hospital, Ibaraki, Japan."), [Yukihiro Akeda](https://pubmed.ncbi.nlm.nih.gov/?term=Akeda+Y&cauthor_id=42759251)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42759251/#short-view-affiliation-9 "Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Graduate School of Medicine, The University of Osaka, Osaka, Japan; Research Institute for Microbial Diseases, The University of Osaka, Osaka, Japan; Chulalongkorn University, Bangkok, Thailand.") ### Affiliations * 1 Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. Electronic address: nakao.ry@jihs.go.jp. * 2 Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan. * 3 Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. * 4 Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Research Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. * 5 Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Research and Education Center for Prevention of Global Infectious Diseases of Animals, Tokyo University of Agriculture and Technology, Tokyo, Japan. * 6 Graduate School of Medicine, Nagoya University, Aichi, Japan. * 7 Osaka Institute of Public Health, Osaka, Japan. * 8 Tsuchiura Kyodo General Hospital, Ibaraki, Japan. * 9 Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Graduate School of Medicine, The University of Osaka, Osaka, Japan; Research Institute for Microbial Diseases, The University of Osaka, Osaka, Japan; Chulalongkorn University, Bangkok, Thailand. * PMID: **42759251** * DOI: [ 10.1016/j.vaccine.2026.129142 ](https://doi.org/10.1016/j.vaccine.2026.129142) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Prime-boost vaccination using different administration routes may enhance protective immunity compared with homologous regimens. Here, we evaluated all eight possible three-dose combinations of intranasal (IN) and subcutaneous (SC) immunization using a glycoengineered membrane vesicle vaccine derived from probiotic Escherichia coli and displaying pneumococcal capsular polysaccharide. This self-adjuvanting vaccine platform induced robust humoral responses regardless of administration route. While all regimens elicited serum IgG responses, only IN-IN-IN, IN-IN-SC, and SC-IN-IN induced strong mucosal SIgA responses and enhanced pneumococcal clearance in the nasal cavity. Among these, the heterologous IN-IN-SC regimen generated the balanced mucosal and systemic immunity and exhibited the highest opsonophagocytic activity. These findings support route optimization as a practical strategy for maximizing the efficacy of glycoengineered membrane vesicle vaccines. **Keywords:** Bacterial membrane vesicles; Mucosal immunity; Pneumococcal vaccine; Prime-boost vaccination; Probiotic Escherichia coli; Vaccination route. Copyright © 2026. Published by Elsevier Ltd. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Distinct humoral responses induced by heterologous versus homologous prime-boost immunization strategies in early life. ](https://pubmed.ncbi.nlm.nih.gov/40852712/) Foroutan Pajoohian P, Aradottir Pind AA, Molina Estupiñan JL, Christensen D, Pedersen GK, Olafsdottir TA, Jonsdottir I, Bjarnarson SP.Foroutan Pajoohian P, et al.Front Immunol. 2025 Aug 7;16:1563345. doi: 10.3389/fimmu.2025.1563345. eCollection 2025.Front Immunol. 2025.PMID: 40852712Free PMC article. * [ Mucosal immunity elicited by a human-Fcγ receptor-I targeted intranasal vaccine platform enhances resistance against nasopharyngeal colonization of Streptococcus pneumoniae and induces broadly protective immunity against respiratory pathogens. ](https://pubmed.ncbi.nlm.nih.gov/39823848/) Kumar S, Hazlett K, Bai G.Kumar S, et al.Vaccine. 2025 Feb 27;48:126729. doi: 10.1016/j.vaccine.2025.126729. Epub 2025 Jan 16.Vaccine. 2025.PMID: 39823848 * [ Mucosal vaccination with outer membrane vesic
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