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Review
. 2023 Nov;11(11):e1819-e1826.
doi: 10.1016/S2214-109X(23)00421-7.

Clinical and regulatory development strategies for Shigella vaccines intended for children younger than 5 years in low-income and middle-income countries

Birgitte K Giersing  1 , Richard Isbrucker  2 , David C Kaslow  3 , Marco Cavaleri  4 , Norman Baylor  5 , Diadié Maiga  6 , Patricia B Pavlinac  7 , Mark S Riddle  8 , Gagandeep Kang  9 , Calman A MacLennan  10
Affiliations
Review

Clinical and regulatory development strategies for Shigella vaccines intended for children younger than 5 years in low-income and middle-income countries

Birgitte K Giersing et al. Lancet Glob Health. 2023 Nov.

Abstract

Shigellosis causes considerable public health burden, leading to excess deaths as well as acute and chronic consequences, particularly among children living in low-income and middle-income countries (LMICs). Several Shigella vaccine candidates are advancing in clinical trials and offer promise. Although multiple target populations might benefit from a Shigella vaccine, the primary strategic goal of WHO is to accelerate the development and accessibility of safe, effective, and affordable Shigella vaccines that reduce mortality and morbidity in children younger than 5 years living in LMICs. WHO consulted with regulators and policy makers at national, regional, and global levels to evaluate pathways that could accelerate regulatory approval in this priority population. Special consideration was given to surrogate efficacy biomarkers, the role of controlled human infection models, and the establishment of correlates of protection. A field efficacy study in children younger than 5 years in LMICs is needed to ensure introduction in this priority population.

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Conflict of interest statement

Declaration of interests NB provides regulatory advice to the regulated industry. PBP receives funding from the Bill & Melinda Gates Foundation for Enterics for Global Health Shigella surveillance. DCK received funding from the Bill & Melinda Gates Foundation while at PATH, and chaired the WHO Product Development for Vaccines Advisory Committee until 2022. MSR consulted for Emergent Biosolutions and Limmatech Biologics while at the University of Nevada. All other authors declare no competing interests.

Figures

Figure 1
Figure 1
Potential regulatory approval pathway for a Shigella vaccine intended for use in adult populations in high-income countries who are exposed to high-risk settings The CHIM studies are interchangeable and could be combined to assess efficacy in the same protocol. CHIM=controlled human infection model. FDA=Food and Drug Administration. EMA=European Medicines Agency. *The study might assess more than one dose. †Minimal safety database. ‡Assume proof of concept against both S flexneri 2a and S sonnei will be needed.
Figure 2
Figure 2
Potential regulatory approval pathway based on a traditional efficacy-based pathway for a Shigella vaccine intended to support broad use (based on a global policy recommendation), in infants and children younger than 5 years in LMICs LMIC=low-income or middle-income country. *The study might assess more than one dose.
See this image and copyright information in PMC

References

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