New clinical trial investigates safety and immune response of Invaplex AR-Detox Shigella vaccine

A newly published article outlines the protocol for new phase Ia/b clinical trial for the InvaplexAR-Detox Shigella vaccine co-administered with the dmLT adjuvant in The Netherlands and Zambia, marking an important step in Shigella vaccine development. 

February 2025

Shigella bacteria are a leading cause of severe diarrhoeal disease, particularly in low-resource settings, where they contribute to high rates of morbidity and mortality—especially among young children. Despite the significant global burden, there is currently no licensed vaccine against shigellosis. Estimates suggest that an effective vaccine could prevent 590,000 deaths over the course of 20 years. An effective vaccine would also be crucial in the fight against antimicrobial resistance (AMR), as Shigella infections are increasingly resistant to antibiotic treatments. 

This new publication by EVI-led consortium ShigaPlexIM describes the protocol to be used in the first phase Ia/b clinical trial designed to assess the safety and tolerability of different dosages of the InvaplexAR-Detox vaccine with dmLT adjuvant, as well as evaluate its ability to generate an immune response in healthy adults and compare immune responses across participants in both low-endemic and high-endemic settings (i.e., the Netherlands and Zambia).

The randomised double-blind, placebo-controlled study follows a dose-escalation approach, in which participants will receive increasing dosages of the vaccine to determine the optimal balance between safety and immune activation.

Developing an effective Shigella vaccine has been challenging due to the low immunogenicity and protective efficacy observed in infants and young children with other vaccine candidates under development. Additionally, vaccine responses may be weaker in highly endemic regions compared to areas with lower exposure—a phenomenon known as "vaccine hyporesponsiveness". The vaccine is being tested with dmLT, a double-mutant heat-labile toxin adjuvant, which has been shown to enhance both systemic and mucosal immune responses, with the potential to overcome these challenges and improve vaccine efficacy.

The results of this study will provide critical data that may pave the way for larger-scale clinical trials and bring us closer to a much-needed Shigella vaccine. By conducting the study in two distinct populations with different exposure to Shigella infections, researchers will also gain valuable insights into how immune responses may differ geographically, ensuring that future vaccines are effective across diverse communities. 

In addition to advancing the vaccine pipeline for a major diarrhoeal disease, the ShigaPlexIM project also aims to enhance capacity building and foster stronger North-South collaboration in clinical research.

Read the full publication here: https://doi.org/10.3390/vaccines13010048

Trial registration: EU CT number: 2023-506394-35-02, ClinicalTrials.gov identifier: NCT05961059.

This project is part of the EDCTP2 Programme supported by the European Union (RIA2018V-2308)