Development and evaluation of granules containing Lactobacillus harboring EV71's cellular receptor

Cooperating countries: Vietnam and Austria

Coordinating institution: Clemens Karl Peterbauer, Universität für Bodenkultur Wien

Partner institutions: Tran Thuoc Linh, University of Science - Ho Chi Minh

Project duration: 1 September 2021 - 31 August 2026

Hand, foot and mouth disease (HFMD) is a common viral disease characterized by symptoms including fever, painful sores and rashes. The disease is mostly mild and occurs mainly in children under 10 years old, but can also appear in adolescents and adults. The dominant cause is a group of enteroviruses including Coxsackie A16 and Enterovirus 71 (EV71). Particularly HFMD caused by EV71 can cause severe symptoms in children and has been associated with complications such as meningitis and encephalitis. There has been a significant increase in EV71 epidemic activity throughout the Asia – Pacific region since 1997.

There is no specific prevention – including a vaccine – available for HFMD until now, and hundreds of thousands of cases are reported annually, putting a burden on society. Several significant milestones in vaccine development have been reached recently; in contrast to that, there has been little progress on preventive approaches like blocking virus entry to targeted cells. Such approaches are cost-effective for resource-limited countries but the drug’s effectiveness is highly dependent on the timing of the treatment.

We will pursue a strategy to block the entry of the virus to its cellular receptor. Human scavenger receptor class B member 2 (hSCARB2) is a cellular receptor for EV71 and CVA16. The region from amino acids 142 to 204 has been shown to be important for EV71 binding and infection, and there are no potential N-glycosylation sites in that region. Recently, E. coli derived, soluble, recombinant SCARB2 has been shown to interact with EV71 in vitro. However, whether the recombinant SCARB2 blocks EV71 infection in vivo remains elusive. In order to use recombinant SCARB2 as a preventive reagent in humans, the receptor has to be used in non GMO or food-grade format. Our research project is focusing on producing recombinant SCARB2 and attaching it onto Lactobacillus plantarum cell membranes using LysM domains, or by directly expressing it in L. plantarum, to use as a bait to prevent virus infection and spreading.

As has been clarified, “Sustainable Development Goal 3 of the 2030 Agenda for Sustainable Development is to “ensure healthy lives and promoting well-being for all at all ages”. The associated targets aim to reduce the global maternal mortality ratio; end preventable deaths of newborns and children; end the epidemics of AIDS, tuberculosis, malaria and other communicable diseases; reduce mortality from non-communicable diseases; strengthen the prevention and treatment of substance abuse; halve the number of deaths and injuries from road traffic accidents; ensure universal access to sexual and reproductive health-care services; achieve universal health coverage; and reduce the number of deaths and illnesses from hazardous chemicals and pollution.” - quoted from the health and population topic.

Since its appearance, HFMD has put an extreme burden on social healthcare especially in Western Pacific Region, where it returns every year with unpredictable consequences. Preventing its spread is considered unreachable as HFMD utilizes directly transmitted ways. Vaccination is a promising method which is on its phase 3 trial now in China. However, the common causes of HFMD are enteroviruses, raising an alternative prevention based on oral route using probiotics as drugs’ carriers to block virus entry. In other hand, adding probiotics helps strengthen the gut microbiota as well, which is known to play an important role not only in children’s development but also in other aspects of healthcare. This project aims to prevent disease progression, also the spread of infection to others during epidemics, which helps reduce either the number of infected children or economic losses for healthcare system. In terms of society, the ability to prevent outbreaks, reduce the number of deaths due to HFMD will have positive effects on social safeness as well as help uphold the Sustainable Development Goal for reducing child and infant mortality through active healthcare and preventive measures. An important factor could be expanded during this project is the collaboration between the two universities of Europe and South East Asia.