Vaccine development against important bacterial pathogens

Cholera, a serious diarrheal disease caused by Vibrio cholerae, is estimated to cause at least 4 million illnesses and more than 100,000 deaths. Since 2021, cholera has further increased as a global health threat due to climate change with more extreme weather, more wars and political crises, and through these effects and also through Covid-19 increased poverty in many countries.   WHO (World Health Organization) and Global Task Force the WHO and the Global Task Force on Cholera Control (GTFCC) launched in 2017 a major program "Ending Cholera: A Global Roadmap to 2030", which aims to reduce cholera deaths by 90% and eliminate transmission in most countries by 2030. In the WHO's strategy, mass vaccination with oral cholera vaccines (OCV ) is a cornerstone, and the increase in cholera cases together with a major shortage of OCV since 2021 now pose acute threats to this goal.

At our laboratory, we have since 2010 developed a new, simplified OCV, which in collaboration with a large Indian vaccine manufacturer has now (August 2025) been registered (Hillchol) and which can greatly add to the global OCV supply in the world. We are now working on developing a further improved and also completely heat-stable OCV (DuoChol). Preclinical studies have shown that the vaccine, consisting of killed bacteria plus recombinantly produced cholera B subunit (rCTB), is stable at 40°C for at least 21 months. The next phase includes GMP manufacturing and a Phase I clinical trial in 2025 in collaboration with the International Vaccine Institute (IVI, South Korea) and with support from the Wellcome Trust. This project involves technology transfer, process optimization, analytical assay development and clinical evaluation of the vaccine.

Another important intestinal pathogen both for children in LMICs and for travelers to these countries is Enterotoxigenic Escherichia coli (ETEC), which together with Vibrio cholerae accounts for over 50% of diarrheal cases globally. ETEC has the highest incidence in children aged 1-3 years, while cholera has the highest mortality in children aged 1-10 years and adults. Both diseases have similar pathogenesis and immunity mechanisms and similar geographic distribution. Our goal is to develop an effective, practical, and heat-stable (cold chain-free) combined oral vaccine against cholera and ETEC diarrhea. The work includes genetic vaccine strain construction, methods for upstream and downstream vaccine production, method analysis development, and in vitro studies of stability and in vivo studies of side effects and immune responses after vaccination.

In addition, we participate in a larger collaborative project with the support of EDCTP (ShigaPlexIM) to conduct phase-1 and phase-2 trials in Europe and Africa respectively of an injectable Shigella vaccine. Shigella is a pathogen with a low infectious dose that is spread through contaminated food and water and for which there is not yet a vaccine. Our work focuses on the development and validation of the immunological analyses that will be used to assess the immune response to a US-produced candidate vaccine and the transfer of these methods to clinical trial centers in the Netherlands and Zambia and Burkina Faso for phase 1 studies to be carried out in 2025.