Journal
DIABETES
Volume 70, Issue 12, Pages 2871-2878Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db21-0193
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Funding
- Barndiabetesfonden (Swedish Child Diabetes Foundation)
- Diabetesfonden(the Swedish Diabetes Foundation)
- Karolinska Institutet
- Strategic Research Program in Diabetes, Business Finland [1843/31/2014]
- Academy of Finland [309455, 288671]
- Sigrid Juseliuksen Saatio (Sigrid Juselius Foundation)
- Reino Lahtikari Foundation
- JDRF [2-SRA-2017-A-N]
- Academy of Finland (AKA) [288671, 288671, 309455, 309455] Funding Source: Academy of Finland (AKA)
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This study demonstrates that CVB vaccines do not alter islet inflammation or accelerate disease progression in an animal model that spontaneously develops autoimmune type 1 diabetes. However, they can prevent CVB-mediated disease progression in the same model.
Enteroviruses, including the Coxsackievirus Bs (CVB), have been implicated as causal agents in human type 1 diabetes. Immunization of at-risk individuals with a CVB vaccine provides an attractive strategy for elucidating the role of CVBs in the disease etiology. Previously, we have shown that an inactivated whole-virus vaccine covering all CVB serotypes (CVB1-6) is safe to administer and highly immunogenic in preclinical models, including nonhuman primates. Before initiating clinical trials with this type of vaccine, it was also important to address 1) whether the vaccine itself induces adverse immune reactions, including accelerating diabetes onset in a diabetes-prone host, and 2) whether the vaccine can prevent CVB-induced diabetes in a well-established disease model. Here, we present results from studies in which female NOD mice were left untreated, mock-vaccinated, or vaccinated with CVB1-6 vaccine and monitored for insulitis occurrence or diabetes development. We demonstrate that vaccination induces virus-neutralizing antibodies without altering insulitis scores or the onset of diabetes. We also show that NOD mice vaccinated with a CVB1 vaccine are protected from CVB-induced accelerated disease onset. Taken together, these studies show that CVB vaccines do not alter islet inflammation or accelerate disease progression in an animal model that spontaneously develops autoimmune type 1 diabetes. However, they can prevent CVB-mediated disease progression in the samemodel.
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