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Toward a Multivalent Synthetic Oligosaccharide-Based Conjugate Vaccine against Shigella: State-of-the-Art for a Monovalent Prototype and Challenges

Armelle Phalipon 1, * Laurence A Mulard 2, * 
* Corresponding author
1 Laboratoire d’innovation : vaccins – Innovation lab : vaccines
Institut Pasteur [Paris], UPC - Université Paris Cité
Abstract : This review focuses on the molecular glycovaccine concept, a promising option to develop a Shigella glycoconjugate vaccine. Subsequent to original developments involving, as main vaccine component, the detoxified Shigella lipopolysaccharide randomly conjugated at multiple sites to a carrier protein, novelty stems from the use of rationally designed, well-defined chemically synthesized oligosaccharide haptens conceived as functional surrogates of the main surface antigen, linked via single-point attachment onto a carrier. The concept and design of such a fine-tuned Shigella glycovaccine are presented by way of SF2a-TT15, a neoglycoprotein featuring a synthetic 15-mer oligosaccharide, which constitutes an original vaccine prototype targeting Shigella flexneri 2a, one of the predominant circulating strains in endemic settings. The clinical testing of SF2a-TT15 is summarized with the first-in-human phase I trial in young healthy adults showing a good safety profile and tolerability, while inducing bactericidal antibodies towards S. flexneri 2a bacteria. The proof-of-concept of this novel approach being established, an ongoing phase IIa clinical study in the nine-month-old infant target population in endemic area was launched, which is also outlined. Lastly, some challenges to move forward this original approach toward a multivalent cost-effective Shigella synthetic glycan conjugate vaccine are introduced.
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Submitted on : Monday, June 20, 2022 - 3:19:48 PM
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Armelle Phalipon, Laurence A Mulard. Toward a Multivalent Synthetic Oligosaccharide-Based Conjugate Vaccine against Shigella: State-of-the-Art for a Monovalent Prototype and Challenges. Vaccines, MDPI, 2022, Special Issue Frontiers in Shigella Vaccine Development, 10 (3), pp.403. ⟨10.3390/vaccines10030403⟩. ⟨pasteur-03699792⟩

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