INTRODUCTION

Virus infections have long been considered as a possible cause of type 1 diabetes. One virus group, enteroviruses (EVs), has been studied extensively, and clinical development of a vaccine against T1D-associated EV types has started.

“Epidemiological and experimental studies indicate that approximately half of all T1D cases could be triggered by a CVB infection in early childhood,” said Dr. Francisco Leon, Provention’s co-founder and Chief Scientific Officer.

“Based on this groundbreaking research, Provention Bio is advancing PRV-101 as the first-ever CVB vaccine designed to prevent acute infection and potentially T1D.  In addition to the potential prevention of T1D, this vaccine could have other important beneficial health effects generated by protection against acute CVB infections, which are frequent and cause significant morbidity particularly in young children.”

Research

A peer-reviewed article published in Expert Review of Vaccines (link) highlights research that pinpoints enterovirus infections, specifically CVB, as a possible cause of T1D.  The article further describes ongoing progress on what could be the first human vaccine for T1D, PRV-101.  PRV-101 is a polyvalent vaccine currently being developed by Provention as a vaccine for acute coxsackie infection and to potentially prevent up to 50% of worldwide T1D cases.  PRV-101 is currently in an IND-enabling stage prior to the initiation of first-in-human studies.

Researcher Heikki Hyöty of the University of Tampere in Finland, who co-authored the current review, had previously found that people with markers of EV infections had an increased risk of Type 1 diabetes. He published that evidence in a 2017 paper in the journal Diabetologia.

In that study, Finnish scientists examined 1,673 longitudinal stool samples from 129 children who turned positive for autoantibodies against pancreatic islets—which is known as a pre-symptom phase of Type 1 diabetes—and compared them with 3,108 samples from 282 matched control children. The researchers observed an increased frequency of EV RNA in the children long before the emergence of autoimmunity.

What’s more, Hyöty and colleagues found that CVB1 antibodies in the mothers of the study subjects were associated with about 50% lower rate of autoimmunity in the children.

“This important observation suggests that a vaccine against CVB could prevent a substantial subset of T1D cases,” wrote the authors in the current study.

Still, there isn’t enough evidence to prove the observed CVB-diabetes link is indeed causal. That key question will be answered by the Provention Bio clinical trial.

Company

Provention Bio, Inc. (Nasdaq: PRVB), a clinical-stage biopharmaceutical company dedicated to developing novel therapeutics aimed at intercepting and preventing immune-mediated diseases.  Provention raised $50 million in an IPO in the Summer of 2018.

The company has developed PRV-101, a multivalent CVB vaccine made with the same formalin-inactivated whole-virus vaccine technology used in a polio inoculation. In a preclinical proof-of-concept study done by a team at the University of Tampere, a prototype of the vaccine successfully protected against virus-induced diabetes in a mouse model of Type 1 diabetes, the team reported in a Diabetologia paper.

“In addition to the potential prevention of T1D, this vaccine could have other important beneficial health effects generated by protection against acute CVB infections, which are frequent and cause significant morbidity particularly in young children.” 

Manufacturing of a clinical CVB vaccine, as well as preclinical studies, are currently in progress in order to enable clinical testing of the first CVB vaccine. Ongoing scientific research projects can significantly facilitate this effort by providing insights into the mechanisms of the CVB-T1D association.

See www.proventionbio.com.