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Coxsackievirus B Vaccines Prevent Infection-Accelerated Diabetes in NOD Mice and Have No Disease-Inducing Effect

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posted on 14.09.2021, 21:10 by Virginia M Stone, Marta Butrym, Minna M Hankaniemi, Amir-Babak Sioofy-Khojine, Vesa P Hytönen, Heikki Hyöty, Malin Flodström-Tullberg
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 non-human primates. Before initiating clinical trials with this type of vaccine it was also important to address whether a) the vaccine itself induces adverse immune reactions including accelerating diabetes onset in a diabetes prone host and b) 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 same model.

Funding

We would like to acknowledge financial support from the Swedish Child Diabetes Foundation, the Swedish Diabetes Foundation, Karolinska Institutet including the Strategic Research Program in Diabetes, the Business Finland (formerly TEKES; THERDIAB project, diary no. 1843/31/2014), the Academy of Finland (grant 309455 awarded to MMH and grant 288671 awarded to HH), the Sigrid Jusélius Foundation, the Reino Lahtikari Foundation and the JDRF (2-SRA-2017-A-N).

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