Recent Scientific Advances in Vaccines for Shigella

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: 30 June 2025 | Viewed by 1160

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Guest Editor
Center for Infectious Disease Research, Bacterial Diseases Branch, Department of Diarrheal Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA
Interests: shigella; salmonella; diarrhea; enteric disease; enteric vaccines; global health

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Guest Editor
Center for Infectious Disease Research, Bacterial Diseases Branch, Department of Diarrheal Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA
Interests: vaccines; immunology; enterics; B cells; global health; correlates of protection

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Guest Editor
Center for Infectious Disease Research, Bacterial Diseases Branch, Department of Diarrheal Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA
Interests: enteric; vaccines; immunology; antibodies; T cells; B cells

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Guest Editor
Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Interests: global health; enteric disease epidemiology; enteric vaccines; mucosal immunity; vaccine adjuvants; vaccine delivery
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Special Issue Information

Dear Colleagues,

Diarrheal disease is a major global health problem, especially for children in low- to middle-income countries. Shigella is the leading etiology of diarrhea-associated mortality in children under 5 years of age and the second-leading etiology of diarrhea-associated mortality across all age groups. Shigella is also an important cause of Traveler’s diarrhea and has been associated with several post-infectious sequelae such as reactive arthritis and irritable bowel syndrome (IBS).

Antibiotic treatment is commonly prescribed for shigellosis, but the global spread of antimicrobial-resistant (AMR) Shigella strains threatens this treatment option. Accordingly, the World Health Organization (WHO) has designated Shigella spp. as Priority Pathogens for the development of new therapeutics or preventive measures. The development of an effective vaccine against Shigella represents the ideal solution to the intertwined global health issues of shigellosis and the rise in AMR Shigella.

A variety of Shigella vaccine candidates are in clinical testing, including conjugate vaccines, outer membrane vesicles, recombinant subunit vaccines, and live attenuated vaccines. In addition, the preclinical pipeline contains several more vaccine candidates, including killed whole-cell vaccines and multi-pathogen (combination) vaccines. This Special Issue will feature the latest advances in the Shigella vaccine field. We invite contributions regarding preclinical vaccine development and clinical findings, as well as assay development for the evaluation of vaccine immunogenicity and potential correlates of protection.

Dr. Akamol E. Suvarnapunya
Dr. Kristen A Clarkson
Dr. Renee M. Laird
Dr. August Louis Bourgeois
Guest Editors

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Keywords

  • Shigella
  • vaccines
  • global health

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Published Papers (1 paper)

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12 pages, 517 KiB  
Study Protocol
Safety, Tolerability, and Immunogenicity of the InvaplexAR-Detox Shigella Vaccine Co-Administered with the dmLT Adjuvant in Dutch and Zambian Adults: Study Protocol for a Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase Ia/b Clinical Trial
by Geert V. T. Roozen, Nsofwa Sukwa, Masuzyo Chirwa, Jessica A. White, Marcus Estrada, Nicole Maier, Kevin R. Turbyfill, Renee M. Laird, Akamol E. Suvarnapunya, Aicha Sayeh, Flavia D’Alessio, Candice Marion, Laura Pattacini, Marie-Astrid Hoogerwerf, Rajagopal Murugan, Manuela Terrinoni, Jan R. Holmgren, Sodiomon B. Sirima, Sophie Houard, Michelo Simuyandi and Meta Roestenbergadd Show full author list remove Hide full author list
Vaccines 2025, 13(1), 48; https://doi.org/10.3390/vaccines13010048 - 8 Jan 2025
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Abstract
Background: Shigella infections remain endemic in places with poor sanitation and are a leading cause of diarrheal mortality globally, as well as a major contributor to gut enteropathy and stunting. There are currently no licensed vaccines for shigellosis but it has been estimated [...] Read more.
Background: Shigella infections remain endemic in places with poor sanitation and are a leading cause of diarrheal mortality globally, as well as a major contributor to gut enteropathy and stunting. There are currently no licensed vaccines for shigellosis but it has been estimated that an effective vaccine could avert 590,000 deaths over a 20-year period. A challenge to effective Shigella vaccine development has been the low immunogenicity and protective efficacy of candidate Shigella vaccines in infants and young children. Additionally, a new vaccine might be less immunogenic in a highly endemic setting compared to a low endemic setting (“vaccine hyporesponsiveness”). The use of a potent adjuvant enhancing both mucosal and systemic immunity might overcome these problems. InvaplexAR-Detox is an injectable Shigella vaccine that uses a novel combination of conserved invasion plasmid antigen proteins and a serotype-specific bacterial lipopolysaccharide attenuated for safe intramuscular administration. The adjuvant dmLT has been shown to enhance Shigella immune responses in mice, has safely been administered intramuscularly, and was shown to enhance immune responses in healthy volunteers when given in combination with other antigens in phase I trials. This article describes the protocol of a study that will be the first to assess the safety, tolerability, and immunogenicity of InvaplexAR-Detox co-administered with dmLT in healthy adults in low-endemic and high-endemic settings. Methods: In a multi-center, randomized, double-blind, and placebo-controlled dose-escalation phase Ia/b trial, the safety, tolerability, and immunogenicity of three intramuscular vaccinations administered 4 weeks apart with 2.5 µg or 10 µg of InvaplexAR-Detox vaccine, alone or in combination with 0.1 µg of the dmLT adjuvant, will first be assessed in a total of 50 healthy Dutch adults (phase Ia) and subsequently in 35 healthy Zambian adults (phase Ib) aged 18–50 years. The primary outcome is safety, and secondary outcomes are humoral and cellular immune responses to the adjuvanted or non-adjuvanted vaccine. Discussion: This trial is part of the ShigaPlexIM project that aims to advance the early clinical development of an injectable Shigella vaccine and to make the vaccine available for late-stage clinical development. This trial addresses the issue of hyporesponsiveness in an early stage of clinical development by testing the vaccine and adjuvant in an endemic setting (Zambia) after the first-in-human administration and the dose-escalation has proven safe and tolerable in a low-endemic setting (Netherlands). Besides strengthening the vaccine pipeline against a major diarrheal disease, another goal of the ShigaPlexIM project is to stimulate capacity building and strengthen global North-South relations in clinical research. Trial registration: EU CT number: 2023-506394-35-02, ClinicalTrials.gov identifier: NCT05961059. Full article
(This article belongs to the Special Issue Recent Scientific Advances in Vaccines for Shigella)
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