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The rotavirus (RV) vaccine could have a surprising off-target effect: protecting against type 1 diabetes. New cases of the autoimmune condition decreased among Australian children after the vaccine was introduced, according to an analysis recently published in JAMA Pediatrics. It’s the first epidemiological evidence of the association.
Why Is This Important?
There’s currently no way to prevent type 1 diabetes. Scientists think unknown environmental exposures trigger the condition in genetically predisposed people. Finding 1 of those triggers could lend important insight into what causes type 1 diabetes and how to prevent it.
Why Focus on Rotavirus?
This wasn’t a shot in the dark. The authors previously linked rotavirus infection—the most common cause of gastroenteritis in children—to diabetes-associated antibodies in genetically susceptible kids. In mice, they found that the virus triggers pancreatic cell death and transient hyperglycemia. A rotavirus surface protein called VP7 structurally resembles pancreatic β-cell autoantigens involved in the development of type 1 diabetes, and this so-called molecular mimicry could confuse the immune system into launching an attack.
It’s therefore plausible that a vaccine against rotavirus infection could also protect against type 1 diabetes. On the other hand, such molecular mimicry might suggest that the vaccine could promote the condition.
In Australia, new type 1 diabetes cases are registered so that the national health system can subsidize glucose testing and insulin supplies. Researchers mined publicly available data to determine rates of new-onset type 1 diabetes from 2000 through 2015 among children up to age 14 years.
What We’ve Learned
There were 16 159 new cases of type 1 diabetes in Australia during the study period. New cases decreased by 14% among children up to age 4 years after the oral rotavirus vaccine for infants was introduced in 2007 as part of the routine immunization schedule. But cases didn’t decline in older kids, most of whom weren’t immunized.
Words of Wisdom
“If our findings are confirmed, they would indicate that rotavirus infection is one environmental factor that can promote development of type 1 diabetes in genetically susceptible children,” said senior author Leonard C. Harrison, MD, of the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia.
“The corollary is that rotavirus vaccination would prevent type 1 diabetes in a proportion of these children,” he added.
What We Still Don’t Know
It’s too soon to conclude that the observed association was causal. It’s possible that some other change occurred around the same time the vaccine was introduced and led to the decrease in type 1 diabetes cases.
The jury is out on whether the decline in new-onset type 1 diabetes will persist as the children get older—a question for ongoing surveillance.
It’s also unclear if the negative association between rotavirus vaccination and type 1 diabetes holds true for children in other countries. A small case-control study in Finland involving just 495 kids didn’t reveal the same link. As the Australian authors wrote in their study, “It is possible that response to RV vaccination could vary by geographical location owing to genetic and environmental differences at the population level.”
If All Bears Out…
According to Harrison, if the observed effect persists throughout life, Australia will have 110 new cases of type 1 diabetes each year instead of 130. “The absolute numbers would of course be substantially higher in the US population if the putative effect occurred there,” he said.
The researchers are working to validate their findings in a case-control linkage study using electronic health records. This time, they’ll look at rates of rotavirus vaccination in Australian children up to age 10 years both with and without type 1 diabetes. The results should be available later this year.
They’ll also conduct a longitudinal study of genetically at-risk children to see if pancreas size is reduced after rotavirus infection. They’ve already shown this in mice, while other investigators have reported that the pancreas is smaller than normal in children with type 1 diabetes.
Abbasi J. Quick Uptakes: After Rotavirus Vaccine, Australia’s Type 1 Diabetes Incidence Declines. JAMA. 2019;321(13):1241–1242. doi:10.1001/jama.2019.0766
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