Vaccine Aims to Lower Type 1 Diabetes Incidence

New vaccines targeting CVB viruses linked with type 1 diabetes may offer protection to patients with high-risk factors.  

The exact etiology of type 1 diabetes mellitus (T1DM) remains unclear, with previous studies suggesting only correlational relationships between possible influencers such as genetics, viral infections, and other environmental factors. Nevertheless, strong hypotheses suggest these influencers are causal factors with real potential when considering prevention strategies like vaccinations. For instance, the Coxsackie B virus (CVB), a subgroup within the enteroviruses, has been linked to T1DM and is thought to play a crucial role in eliciting the autoimmune response attack on the body’s pancreatic beta cells. The strain most associated with beta-cell autoimmunity is CVB1, with others responsible for myocarditis and encephalitis conditions. Previously, there have been limited efforts to target this virus. Thus, developing a vaccine that can protect against the infection and its six identified strains could have significant impact. 

Researchers at Karolinska Institute and two universities in Finland, the University of Jyväskylä and Tampere, are currently working on a vaccine capable of producing immunogenicity to the six CVB serotypes to prevent complications arising from these infections, one of which includes T1DM. The group published their findings in the journal ScienceAdvance outlining the vaccine’s efficacy and safety profile using murine mice and primate models. The preclinical data included primary outcomes focused on antibody response and adverse event characteristics. Secondary outcomes followed rates of acute CVB infections, most notably myocarditis, and clinically relevant CVB induced diseases such as CVB-induced diabetes. Researchers tracked rates of new-onset diabetes within both animal models by regularly monitoring blood glucose levels following infections. Subjects with two blood glucose readings over 234mg/dL. (13mmol/L) or one over 300mg/dL. (18mmol/L) were considered diabetic. 

The study determined that the vaccine had an excellent safety profile with no adverse events observed. Researchers used a Mann-Whitney U test to show no statistically significant body mass changes between the control and vaccinated subjects. From the immunogenicity studied, titers displayed a strong neutralizing antibody response to all six CVB strands following the first booster given on day 14. Antibody levels remained consistently high for all but one subject, amplified by each sequential booster and persisting until the experiment ended. The study compared acute infection rates between mock-vaccinated and vaccinated subjects. Results showed that nearly 80% of the mock-vaccinated group became viremic when infected with CVB1 strand, and 100% were viremic when challenged with CVB4. 

Moreover, researchers found that the virus was replicating in the bloodstream and the pancreas. Assays tested positive for viral protein in 75% of those infected by CVB1 and 100% affected by CVB4. Alternatively, vaccinated subjects had no viral replication present within the bloodstream. The vaccine prevented viral infiltration to the pancreas in 75% of the CVB1 infected models and 100% in the CVB4 infected models. Rates of CVB-induced diabetes were studied to find whether the vaccine could offer a source of prevention. Mock-vaccinated subjects developed hyperglycemia shortly following CVB1 or CVB3 infections, demonstrated by a sharp rise of blood glucose by 50 to 100%. The group also displayed signs of damage to pancreatic tissue following infection. Vaccinated groups exhibited none of these signs, appearing protected with stable blood glucose levels and healthy pancreatic tissue. 

The study provides more evidence that CVB infections may lead to the development of type 1 diabetes. From this, vaccinations could play a key role in reducing incidence by providing primary prevention. However,  because the study only provides preclinical data, human trials producing evidence on the vaccine’s safety and efficacy are still needed. These clinical trials are currently in progress by an American pharmaceutical company. If the results remain consistent with previous data, then the use of this vaccine can potentially reduce diabetes rates and illustrate the extent to which CVB infections influence diabetes prevalence.  

Practice Pearls: 

• Coxsackie B Virus is linked to the development of type 1 diabetes following infection. 
• Clinical trials for the development of a CVB vaccine are currently in progress. 
• The vaccine could reduce the incidence of type 1 diabetes in the future. 

University of Jyväskylä – Jyväskylän yliopisto. “Possible vaccine for virus linked to type 1 diabetes.” ScienceDaily. ScienceDaily, 7 May 2020.  

Stone, V. M., et al. “A Hexavalent Coxsackievirus B Vaccine Is Highly Immunogenic and Has a Strong Protective Capacity in Mice and Nonhuman Primates.”  American Association for the Advancement of Science, May 1, 2020.  

Stephen Rubano, PharmD. Candidate, USF Taneja College of Pharmacy