Dataset from Efficacy, Safety and Immunogenicity of GVGH Shigella Sonnei Vaccine (1790GAHB) in a Human Challenge Study of Healthy Non-immune Adults

The purpose of this study is to evaluate the efficacy, safety and immunogenicity of the
GSK3536852A vaccine, which was designed to protect against shigellosis caused by Shigella
sonnei (S. sonnei) and is using the new Generalized Modules for Membrane Antigens (GMMA)
platform technology developed by GlaxoSmithKline (GSK) Vaccines Institute for Global Health
(GVGH).

The study vaccine could be the stepping stone for the development of a multivalent broadly
protective Shigella vaccine for vaccination of impoverished communities where shigellosis is
endemic. However, a standalone monovalent vaccine against S. sonnei could be used to protect
travelers against diarrheal shigellosis, as the vast majority of travelers' shigellosis is
caused by S. sonnei, and even to protect infants in endemic regions where shigellosis is
primarily caused by S. sonnei.

The GSK3536852A vaccine has been tested in two Phase I dose escalation studies in Europe to
assess its safety and immunogenicity via three routes of administration: intramuscular (IM),
intranasal (IN) and intradermal (ID). The results from the first study (dose escalation with
IM vaccination) have shown that the vaccine has an acceptable safety profile and is
well-tolerated up to a dose of 100 micrograms (µg). The results from the second study (dose
escalation with ID, IN and IM vaccination) showed that GSK3536852A vaccine is well-tolerated
also when administered by the ID and IN routes of vaccination. However, immunogenicity data
have shown that GSK3536852A vaccine administered by the ID and IN routes is not as
immunogenic as GSK3536852A vaccine administered by the IM route. Therefore, it has been
decided to proceed with the clinical development program of this vaccine only using the IM
vaccination route. In terms of dosage, the regimen tested in Phase I studies (three doses
given one month apart) did not show any significant benefit from the third dose in terms of
immunogenicity, therefore a two dose schedule was selected for next studies.

A Phase IIa study, conducted in endemic regions of Africa (i.e., Kenya), has been completed
and confirmed the acceptable safety profile and immunogenicity of GSK3536852A vaccine.

Performing this vaccine-human challenge study may give the opportunity to establish evidence
of clinical protection induced by the candidate S. sonnei vaccine (GSK3536852A vaccine) at an
early development stage.