A next-generation GMMA-based vaccine candidate to fight shigellosis.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
05 Sep 2023
05 Sep 2023
Historique:
received:
11
04
2023
accepted:
04
08
2023
medline:
6
9
2023
pubmed:
6
9
2023
entrez:
5
9
2023
Statut:
epublish
Résumé
Shigellosis is a leading cause of diarrheal disease in low-middle-income countries (LMICs). Effective vaccines will help to reduce the disease burden, exacerbated by increasing antibiotic resistance, in the most susceptible population represented by young children. A challenge for a broadly protective vaccine against shigellosis is to cover the most epidemiologically relevant serotypes among >50 Shigella serotypes circulating worldwide. The GMMA platform has been proposed as an innovative delivery system for Shigella O-antigens, and we have developed a 4-component vaccine against S. sonnei, S. flexneri 1b, 2a and 3a identified among the most prevalent Shigella serotypes in LMICs. Driven by the immunogenicity results obtained in clinic with a first-generation mono-component vaccine, a new S. sonnei GMMA construct was generated and combined with three S. flexneri GMMA in a 4-component Alhydrogel formulation (altSonflex1-2-3). This formulation was highly immunogenic, with no evidence of negative antigenic interference in mice and rabbits. The vaccine induced bactericidal antibodies also against heterologous Shigella strains carrying O-antigens different from those included in the vaccine. The Monocyte Activation Test used to evaluate the potential reactogenicity of the vaccine formulation revealed no differences compared to the S. sonnei mono-component vaccine, shown to be safe in several clinical trials in adults. A GLP toxicology study in rabbits confirmed that the vaccine was well tolerated. The preclinical study results support the clinical evaluation of altSonflex1-2-3 in healthy populations, and a phase 1-2 clinical trial is currently ongoing.
Identifiants
pubmed: 37670042
doi: 10.1038/s41541-023-00725-8
pii: 10.1038/s41541-023-00725-8
pmc: PMC10480147
doi:
Types de publication
Journal Article
Langues
eng
Pagination
130Subventions
Organisme : Bill & Melinda Gates Foundation
ID : INV-006482
Pays : United States
Informations de copyright
© 2023. Springer Nature Limited.
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