Clinical Microbiology: Open Access

Safety and immunogenicity of a synthetic carbohydrate-based conjugate vaccine against bacillary dysentery assessed in a phase-I study in healthy adult volunteers

8^thGlobal Summit on Microbiology and Infectious Diseases

February 22-23, 2018 | Paris, France

Armelle Phalipon, D Cohen, J Atsmon, C Artaud, S Meron-Sudai, M L Gougeon, A Bialik, S Goren, V Asato, O Ariel-Cohen, A Reizis, A Dorman, I Volokhov, D Shaikevich, C W G Hoitink, J Westdijk, S Ashkenazi, P Sansonetti and L A Mulard

Institut Pasteur, France
Tel Aviv University, Israel
Tel Aviv Sourasky Medical Center, Israel
Intravacc, Netherlands
Schneider Children′s Hospital, Israel

Posters & Accepted Abstracts: Clin Microbiol

Abstract:

Glycoconjugates incorporating detoxified LPS from Shigella flexneri 2a or Shigella sonnei, the two main strains responsible for the endemic form of bacillary dysentery, have been shown to be safe and immunogenic in healthy volunteers. Phase III trials have demonstrated the protective capacity of a S. sonnei detoxified LPS-conjugate against S. sonnei infection in young adults and children older than 2 years of age. The search for a highly immunogenic S. flexneri 2a vaccine, able to generate protective immunity in children below 2 years of age and to get rid of the issues related to LPS detoxification, we have rationally designed SF2a-TT15, a tetanus toxoid (TT) conjugate encompassing a synthetic pentadecasaccharide hapten corresponding to three repeating units of the LPS O-antigen from S. flexneri 2a. In preclinical studies, SF2a-TT15 has been shown to induce anti-LPS bactericidal antibodies. We will detail the results of a first-in-human, single-blinded, observer-masked randomized, dose escalation (2 different doses of the sugar component), placebo-controlled study in healthy Israeli volunteers. In summary, the vaccine candidate is safe and its immunogenicity is very promising. These findings support further evaluation for safety, immunogenicity and protective efficacy in additional settings. The results will be put in the global context of the current development of Shigella subunit vaccines.