Review Article | Published:

Progress and pitfalls in Shigella vaccine research

Nature Reviews Gastroenterology & Hepatology volume 10, pages 245255 (2013) | Download Citation

Abstract

Renewed awareness of the substantial morbidity and mortality that Shigella infection causes among young children in developing countries, combined with technological innovations in vaccinology, has led to the development of novel vaccine strategies in the past 5 years. Along with advancement of classic vaccines in clinical trials and new sophisticated measurements of immunological responses, much new data has been produced, lending promise to the potential for production of safe and effective Shigella vaccines. Herein, we review the latest progress in Shigella vaccine development within the framework of persistent obstacles.

Key points

  • Shigella infection continues to be a leading cause of morbidity and mortality, exerting the greatest burden in children in less-industrialized countries

  • Epidemiological studies (for example, Global Enteric Multicenter Study) confirmed the distribution of multiple serotypes in geographical regions as important causes of infection

  • Studies on Shigella pathogenesis have revealed new virulence factors, which might serve as targets for attenuation in live vaccine strains or as potential vaccine antigens

  • Vaccine strategies can be divided into serotype-targeted or conserved protein antigen approaches and multiple candidates are in various stages of development and evaluation

  • New immunological measurements are shedding light on important protective responses

  • Multiple barriers (such as insufficient funding to accelerate and complete clinical trials) exist that are impeding the pace of Shigella vaccine development

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Acknowledgements

The authors would like to acknowledge funding from the following grants: U19 AI090873 (A. Fasano, E. M. Barry, M. F. Pasetti), U19 AI082655 (CCHI: M. B. Sztein), U54 AI57168 (M. M. Levine, E. M. Barry), R01 AI059223 (E. M. Barry), R01 AI089519 (M. F. Pasetti), grants from the Enteric Vaccine Initiative-Program for Appropriate Technology in Health (M. M. Levine, M. F. Pasetti, E. M. Barry) and grants #38874 and OPP1033572 from the Bill and Melinda Gates Foundation (M. M. Levine, K. L. Kotloff). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the NIH.

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  1. University of Maryland School of Medicine, Center for Vaccine Development, 685 West Baltimore Street, HSF 480, Baltimore, MD 21201, USA

    • Eileen M. Barry
    • , Marcela F. Pasetti
    • , Marcelo B. Sztein
    • , Karen L. Kotloff
    •  & Myron M. Levine
  2.  Mucosal Immunology and Biology Research Center, Massachusetts General Hospital East, Building 114, 16th Street, Charlestown, MA 02129, USA

    • Alessio Fasano

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All authors contributed equally to all aspects of this manuscript.

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https://doi.org/10.1038/nrgastro.2013.12

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