Abstract
Controlled Human Infection Models (CHIMs) now exist for several infectious diseases. CHIMs offer significant insight into disease pathogenesis, as well the potential to rapidly test clinical proof-of-concept of vaccine candidates. The application of CHIMs to identify a correlate of protection that may reduce the sample size of, or obviate the need for clinical efficacy studies to achieve licensure is of considerable interest to vaccine developers and public health stakeholders. This topic was the subject of a workshop at the 2018 Vaccines Against Shigella and ETEC (VASE) conference, in the context of O-antigen-based Shigella vaccines.
Highlights
The use of Controlled Human Infection Models (CHIMs) to inform vaccine development is expanding with several review articles summarizing their application against a broad range of pathogens, including bacteria, viruses, parasites and helminths [1,2]
Proof of concept for field efficacy of O-antigen-based Shigella vaccines was established over 20 years ago with a first-generation conjugate vaccine composed of Shigella sonnei O-specific polysaccharide bound to Pseudomonas aeruginosa recombinant exoprotein A (S. sonnei-rEPA)
It is currently being assessed in a CHIM study in Cincinnati while a quadrivalent vaccine is being produced for a similar phase 1/2a age-descending study as planned for the four-valent bioconjugate
Summary
The use of Controlled Human Infection Models (CHIMs) to inform vaccine development is expanding with several review articles summarizing their application against a broad range of pathogens, including bacteria, viruses, parasites and helminths [1,2]. Large scale trials to formally assess the efficacy and effectiveness of Typbar-TCV are underway, results from these studies will not be reported for several years With these examples as context, there is considerable interest in how CHIM can accelerate licensure for Shigella vaccine candidates. Proof of concept for field efficacy of O-antigen-based Shigella vaccines was established over 20 years ago with a first-generation conjugate vaccine composed of Shigella sonnei O-specific polysaccharide bound to Pseudomonas aeruginosa recombinant exoprotein A (S. sonnei-rEPA) This candidate elicited protective antibodies against surface O-Ag of lipopolysaccharide [15]. It is hoped that the new candidates will demonstrate improved immunogenicity and efficacy in the target population of young children in LMICs. A key question from stakeholders involved in product development is whether CHIM may accelerate their development by confirming efficacy and establishing an immunological threshold of serum O-Ag IgG antibody that could offer protection.
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