Bowel disorder common in low-income countries may impair immune response, mouse study finds

Oral vaccines are unlikely to work for people in low-income countries because a bowel disease common in these countries damages the immune response in the gut, a new study finds.

Researchers in Pittsburgh studied a gut condition linked to poor sanitation by simulating the condition in mice and studying its impact on the immune system.

In the mice with this condition, 18 times fewer vaccine-specific immune system cells developed in the small intestine than in healthy mice.

The findings suggest that oral vaccines for COVID-19 and other diseases may not be effective in the countries that would find these vaccines most useful logistically.

But with better sanitation and antibiotics, the effectiveness of the vaccine can be improved.

Oral vaccines are currently in development for Covid, but they may not work well in low-income countries, new study suggests

As the Indian ‘Delta’ variant wreaks havoc around the world, public health experts have called for Covid vaccines to be more easily available outside of wealthy countries.

To help with this, some scientists are working on oral vaccines.

Israeli company Oravax Medical will start clinical trials for such a vaccine this summer.

And in the US, biotechnology company Vaxart has filed for Food and Drug Administration approval for its own oral vaccine.

Oral vaccines are especially useful in low-income countries that lack the trained health professionals and other resources needed for massive needle-based vaccination campaigns.

But a new study shows why this type of vaccine may not work as well for people living in the countries that need the technology the most.

Researchers at the University of Pittsburgh found that a gut condition common in low-income countries hampers the immune system’s ability to respond to oral vaccines.

For the study, published Tuesday in the journal Immunity, the team targeting a condition called environmental enteric dysfunction (EED) – caused by malnutrition and contaminated food and water.

EED is common in regions with poor sanitation. Infection from contaminated food and water systems — combined with a poor diet — causes intestinal inflammation and damages villi, specialized parts of the gut that absorb nutrients from food.

Worldwide, approximately 150 million children are at risk of EED due to their living conditions.

‘EED can affect anyone, but it is a big problem in children because they are still developing,’ says Dr Timothy Hand, senior author of the study and assistant professor of pediatrics and immunology at the University of Pittsburgh.

“The result is that children with EED are immature. They eventually become smaller in stature.

‘But perhaps more importantly, it can significantly influence brain development: these children have less cognitive ability. And this is a lifelong problem; you can’t restore that development later in life.’

The left side of this image shows a healthy mouse gut, while the right side shows a mouse with EED - the organ is inflamed and the villi are damaged

The left side of this image shows a healthy mouse gut, while the right side shows a mouse with EED – the organ is inflamed and the villi are damaged

Hand and the other researchers modeled EED in mice by feeding the rodents a diet of limited nutrients, combined with Escherichia coli (E. coli) infection.

The intestinal disorder caused serious problems for the immune system of the mice.

About 18 times fewer vaccine-specific immune system cells developed in the small intestine of mice with EED compared to healthy mice

The EED mice also had growth retardation, inflammation in their gut and changes in their gut microbiology compared to healthy mice.

Further investigation showed that the immune system failure was related to the gut microbiome of the mice – the bacteria, fungi and other small organisms that live in the digestive system.

EEd infection caused the guts of the mice to become inflamed, leading to a buildup of T-regulatory (or Treg) cells.

“Treg cells arise because there is too much inflammation and they help slow that inflammation down,” Hand said. ‘But unfortunately a side effect is that they prevent local accumulation of vaccine-specific CD4+ T cells.’

The researchers used antibiotics to treat the mice’s gut bacteria. After this treatment, vaccines were more effective – suggesting that similar treatments may work for humans.

As scientists continue to develop oral vaccines for Covid and other diseases, they need to consider several sanitary and other public health factors in low-income countries.

“If we could get toilets and plumbing for the world, we wouldn’t have this disease,” Hand said.

‘The cause of these chronic infections is that people either drink contaminated water or that flies carry disease from sewage to food.’

Hand and his team plan to continue investigating the impact of EED on vaccine effectiveness by working with researchers in countries with high rates of this disease.

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