Salmonella as a vaccine delivery vehicle

Abstract

Attenuated Salmonella vaccines can be administered orally to deliver recombinant antigens to mucosal surfaces inducing a protective immune response against a variety of targeted pathogens. A number of exciting new approaches and technologies for attenuated Salmonella vaccines have been developed recently. However, a disconnect remains between results obtained with mice in preclinical studies and results obtained in human clinical trials. This is due to an incomplete understanding of Salmonella Typhi interactions with human hosts and inadequate animal models available for study. In this review, the authors describe recent progress in identifying important differences underlying S. Typhi–host interactions, the development of novel approaches to vaccine design and six recent clinical trials evaluating Salmonella-vectored vaccines.

Keywords::

• attenuation strategies
• clinical trials
• murine typhoid models
• recombinant vaccine
• Salmonella-vectored vaccine

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Erratum

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Salmonella Typhi vaccine vectors do not produce strong immune responses in humans. This is not only true for typhoid antigens, but especially for vectored heterologous antigens.

• • A broader understanding of S. Typhi pathogenesis allows researchers to better understand how to attenuate vaccine strains.

• • Predictive correlates for human immunity and reactogenicity must be established to provide a basis for interpreting preclinical data.

• • Development of alternative, relevant animal models will lead to more immunogenic, safer Salmonella-vectored vaccines. Use of these new models will allow more effective screening of vaccine candidates, which should improve the chances for successful clinical trials and development of effective vaccines.

• • Recent research has introduced a variety of new vaccine approaches, including attenuation strategies, antigen synthesis and antigen delivery mechanisms.

• • Recent research has also elucidated some of the key differences between S. Typhi and S. Typhimurium, allowing researchers to design vaccines that take these differences into account.