Shigella and ETEC vaccine pipeline advances despite pandemic slowdown

Feb 22, 2022


Allison Clifford
Communications Manager, PATH's Center for Vaccine Innovation and Access
Health worker in Nepal draws vaccine into a syringe. PATH/Rocky Prajapati

While the world continues to battle COVID-19, it’s encouraging to see that research on other public health priorities is still making strides. Although the development of new interventions for diarrheal diseases has slowed during the pandemic, there are still plenty of advances to celebrate. PATH’s Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Virtual Symposium, held on September 28 and 30, 2021, featured many of these.

Shigella and ETEC are among the leading bacterial causes of diarrhea among children in low- and middle-income countries, causing thousands of deaths and millions of hospitalizations each year. No vaccines against these pathogens exist yet, but recent clinical research on the leading vaccine candidates in the pipeline shows that they are on the way.

Shigella vaccine candidate updates

InvaplexAR-DETOX is a unique, injectable candidate vaccine that uses a novel formulation to target multiple unique structures on the surface of the Shigella bacterium, potentially providing broader protection. A Phase 1 safety and immunogenicity study of InvaplexAR-DETOX in the US was completed in June 2020. It was then followed by exploratory immunology analyses using samples from the study. These analyses, which were completed in 2021, indicate that InvaplexAR-DETOX induces a stronger immune response than has been seen with other Shigella candidate vaccines or after natural or experimental infection.

In addition, two ongoing Phase 1/2 descending-age studies in Kenya with other Shigella vaccine candidates are showing promise. One is testing an injectable, multivalent bioconjugate candidate for safety and immunogenicity. This new type of conjugate vaccine is the first such candidate against Shigella and is targeting the most common serotypes contributing to global illness and death. The other study is testing an injectable, monovalent Shigella flexneri 2a conjugate vaccine candidate, which uses a synthetic Shigella strain-specific “O” carbohydrate conjugated to tetanus toxoid. By conjugating or joining the Shigella molecule with tetanus toxoid, the vaccine may be able to better prevent illness in broader age groups.

A third study in Kenya is also in the works with an injectable, Generalized Modules for Membrane Antigens (GMMA) vaccine candidate called AltSonflex1-2-3. This multi-site Phase 2a descending-age study began in Europe in October 2021 and will expand to Kenya by mid-2022. AltSonflex1-2-3 uses GMMA as a delivery system for a four-component formulation that aims to protect against the major disease-causing Shigella strains.

ETEC vaccine candidate updates

The most advanced oral ETEC vaccine candidate, ETVAX®, recently completed a Phase 2b trial for protection against travelers’ diarrhea among Finnish travelers to Benin. The trial confirmed ETVAX’s excellent safety and immunogenicity for adult travelers, and it will next proceed to Phase 3 studies in this population. In addition, a recently completed Phase 1 descending-age trial of ETVAX in Zambia found that ETVAX was safe, tolerable, and immunogenic in children as well. These results supported the candidate’s advancement to a Phase 2b efficacy trial with children in The Gambia, which is now enrolling participants.

Another promising ETEC vaccine candidate in development is an injectable subunit vaccine candidate called CssBA that recently completed a US-based Phase 1 study. This was the first study to demonstrate the safety and immunogenicity of CssBA given with or without a novel vaccine adjuvant called double-mutant heat-labile toxin (dmLT) when administered intramuscularly. Additional analyses of study samples are ongoing and will further characterize the immune responses, paving the way for future studies and the development of a multivalent subunit ETEC vaccine.

Potential for a combination vaccine

In addition to these exciting pipeline advances, research on combination vaccine approaches to address more than one pathogen in a single vaccine has also progressed. ShigETEC is a novel oral, live attenuated Shigella vaccine candidate that also expresses ETEC enterotoxins. Because of this, it may provide protection against disease caused by both pathogens. ShigETEC was recently evaluated in a Phase 1 trial in Austria and results showed the candidate was safe and well tolerated. Further clinical studies are now being planned to explore this potentially groundbreaking combination vaccine approach.

More to come!

If these updates have piqued your interest, or if you know of other important research not represented here – you’re in luck! PATH recently opened a call for abstracts for the 2022 VASE Conference, which will be held on November 29 to December 1 in Washington, DC. The deadline for submissions is June 9, 2022, and there will be an opportunity to submit late-breaking abstracts.

At this time, VASE 2022 is being planned as an in-person event, so if you are interested in attending but need financial assistance, you can also submit an application for a travel grant. The deadline for applications is August 9, 2022. These grants will be limited to covering economy-class airfare for travel to Washington, DC and lodging at the Renaissance Washington, DC Downtown Hotel for the duration of the conference.

Join us in November at VASE 2022 to learn about more updates on all these vaccine candidates, as well as numerous other research advances from the enteric vaccine field!