ArticlePLoS neglected tropical diseases2021
Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes.
Article in PLoS neglected tropical diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 21 citations in OpenAlex.
- Safety and Immunogenicity of a 4-Component Generalized Modules for Membrane Antigens Shigella Vaccine in Healthy European Adults: Randomized, Phase 1/2 Study.The Journal of infectious diseases · 2024Trial
- Review
- Development and evaluation of a dual-target glycoconjugate againstFrontiers in immunology · 2026Article
- Preclinical evaluation of multivalent vaccine combinations againstFrontiers in immunology · 2026Article
- Protective and pathogenic antibody responses from a primate Shigella outbreak inform vaccine design.bioRxiv : the preprint server for biology · 2025Article
- Evaluation of cross-functional antibody responses elicited by a four-component GMMA Shigella vaccine.NPJ vaccines · 2025Article
- Article
- Antibodies elicited by altSonflex1-2-3 GMMA vaccine are bactericidal against a panel of drug-resistantFrontiers in immunology · 2025Article
- Development and Characterization of a 13-Plex Binding Assay to DetectOpen forum infectious diseases · 2024Article
- Article
- High-Throughput Luminescence-Based Serum Bactericidal Assay Optimization and Characterization to Assess Human Sera Functionality Against MultipleInternational journal of molecular sciences · 2024Article
- A next-generation GMMA-based vaccine candidate to fight shigellosis.NPJ vaccines · 2023Article
- Article
- Characterization of Shigella flexneri Serotype 6 Strains Isolated from Bangladesh and Identification of a New Phylogenetic Cluster.Journal of bacteriology · 2023Article
- P1 Bacteriophage-Enabled Delivery of CRISPR-Cas9 Antimicrobial Activity AgainstACS synthetic biology · 2023Article
- Exploring the Role of GMMA Components in the Immunogenicity of a 4-Valent Vaccine againstInternational journal of molecular sciences · 2023Article
- Functional assays to evaluate antibody-mediated responses againstFrontiers in cellular and infection microbiology · 2023Review
- Comparison ofFrontiers in molecular biosciences · 2023Article
- Setup and Characterization of a High-Throughput Luminescence-Based Serum Bactericidal Assay (L-SBA) to Determine Functionality of Human Sera againstBiotech (Basel (Switzerland)) · 2022Article
- Rapid generation of Shigella flexneri GMMA displaying natural or new and cross-reactive O-Antigens.NPJ vaccines · 2022Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
No vaccine to protect against an estimated 238,000 shigellosis deaths per year is widely available. S. sonnei is the most prevalent Shigella, and multiple serotypes of S. flexneri, which change regionally and globally, also cause significant disease. The leading Shigella vaccine strategies are based on the delivery of serotype specific O-antigens. A strategy to minimize the complexity of a broadly-protective Shigella vaccine is to combine components from S. sonnei with S. flexneri serotypes that induce antibodies with maximum cross-reactivity between different serotypes. We used the GMMA-technology to immunize animal models and generate antisera against 14 S. flexneri subtypes from 8 different serotypes that were tested for binding to and bactericidal activity against a panel of 11 S. flexneri bacteria lines. Some immunogens induced broadly cross-reactive antibodies that interacted with most of the S. flexneri in the panel, while others induced antibodies with narrower specificity. Most cross-reactivity could not be assigned to modifications of the O-antigen, by glucose, acetate or phosphoethanolamine, common to several of the S. flexneri serotypes. This allowed us to revisit the current dogma of cross-reactivity among S. flexneri serotypes suggesting that a broadly protective vaccine is feasible with limited number of appropriately selected components. Thus, we rationally designed a 4-component vaccine selecting GMMA from S. sonnei and S. flexneri 1b, 2a and 3a. The resulting formulation was broadly cross-reactive in mice and rabbits, inducing antibodies that killed all S. flexneri serotypes tested. This study provides the framework for a broadly-protective Shigella vaccine which needs to be verified in human trials.
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