StoneOnlineAppendixEdited_cx01.pdf (564.29 kB)
Coxsackievirus B Vaccines Prevent Infection-Accelerated Diabetes in NOD Mice and Have No Disease-Inducing Effect
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posted on 2021-09-14, 21:10 authored by Virginia M Stone, Marta Butrym, Minna M Hankaniemi, Amir-Babak Sioofy-Khojine, Vesa P Hytönen, Heikki Hyöty, Malin Flodström-TullbergEnteroviruses, 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.