Human microbiome influences rotavirus vaccine response

August 8, 2018, Cell Press
Transmission electron micrograph of intact rotavirus particles, double-shelled Transmission electron micrograph of intact rotavirus particles, double-shelled. Credit: CDC

In a proof-of-concept study in healthy adult men, scientists in the Netherlands found that microbiome manipulation with antibiotics influenced the response to oral rotavirus vaccine. Specifically, they found higher levels of viral shedding in those receiving antibiotic treatment prior to vaccination compared with controls receiving no antibiotic treatment prior to vaccination. The study is a human demonstration that altering the bacterial intestinal microbiome can affect a vaccine's immunogenicity. The results appear August 8 in the journal Cell Host & Microbe.

"We found that the weakened live virus in the replicates at a higher level in antibiotic-treated recipients," says co- first author Vanessa Harris, of the Amsterdam Institute for Global Health and Development and the Division of Infectious Diseases and Center for Experimental and Molecular Medicine at the Amsterdam Medical Center, the Netherlands. "That means more virus was shed and we know from previous research that children who have higher shedding have better protection from the vaccine."

The researchers initiated the study to see if they could corroborate that the is related to vaccine performance. "If that is so, which we believe it is, then one could potentially use the microbiome to improve vaccine performance," says Harris, whose research has focused on the potential correlation between the microbiome and oral vaccine performance.

Rotavirus kills over 200,000 children each year and is the most important cause of diarrheal death in children. Previous research has shown that vaccines protect children against the disease but that they work less well in low-income settings. The reason for this was not well understood.

Working with co-first author Bastiaan Haak, Harris initiated the 63-person study to include healthy male adults randomized into two arms of : either broad spectrum with vancomycin/ciprofloxacin/metronidazole, where all bacteria were essentially killed, or narrow-spectrum with vancomycin. A no-vaccine control arm was also included. After antibiotic treatment and vaccination, subjects were assessed for antibody response and viral shedding. No differences were found in antibody levels between the three treatment arms except a slight increase in early vaccine boosting in the narrow-spectrum arm, but higher viral shedding was noted in the antibiotic-treated groups compared with the control arm.

In the team's earlier field work in children in Ghana and Pakistan, they found that infants with good immunity to the rotavirus vaccine had specific bacteria in their intestine. In this study, they added the vancomycin arm to see if they could replicate some of the microbiome findings found in those earlier field studies.

While the results from this study are limited since rotavirus is a childhood disease and the microbiome of infants and children is different in adults, the researchers are buoyed that their microbiome/vaccine response theory deserves further study.

"I think there is a fascinating interplay between the bacteria and viruses in our intestines and our intestinal immune system," says Harris. "All microbiota in the gut, including bacteria, fungi, and viruses, have evolved together for so long, it is very likely viruses exploit bacteria or immune responses in the gut to their advantage. Perhaps certain bacteria help the rotavirus replicate or alter bacteria and thereby trigger immune responses that are favorable or unfavorable for a virus."

The team believes that understanding that triangulation between , , and the human immune system has potential for vaccinology and can lead to important uses of the microbiome that have not been realized to date.

Harris emphasizes that this work does not advocate for antibiotic use in infants or children to boost rotavirus responses. Instead, the researchers view these results as a starting point with great potential for altering the microbiome to improve vaccine performance and ultimately better protect in low-income settings from rotavirus, which continues to be a life-threatening disease.

Explore further: Immune discovery should help develop improved vaccines for infants and newborns

More information: Cell Host & Microbe, Harris and Haak et al. "Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial." DOI: 10.1016/j.chom.2018.07.005 , http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(18)30375-5

Related Stories

Immune discovery should help develop improved vaccines for infants and newborns

July 10, 2018
Scientists have just identified a class of 'danger signals' that are highly efficient at triggering an immune response in infants and newborns. They believe their discovery may have the potential to reduce both the age of ...

Antibiotic prescriptions in infants may impact the effectiveness of important vaccinations

May 10, 2018
Findings from a South Australian-led study on antibiotic use and the effectiveness of vaccinations could have significant implications for vaccination programs globally.

Rotavirus vaccine could reduce UK health inequalities, new study suggests

January 29, 2018
New research led by the University of Liverpool has found that childhood vaccination against rotavirus has greatest benefit in the most deprived communities and could contribute to reducing health inequalities in the UK.

Antibiotics before birth and in early life can affect long-term health

June 29, 2018
Half of Australian infants have received at least one course of antibiotics by their first birthday. This is one of the highest rates of antibiotic use in the world.

Intestinal bacteria needed for strong flu vaccine responses in mice

September 11, 2014
Mice treated with antibiotics to remove most of their intestinal bacteria or raised under sterile conditions have impaired antibody responses to seasonal influenza vaccination, researchers have found.

Recommended for you

Tibetan sheep highly susceptible to human plague, originates from marmots

August 16, 2018
In the Qinghai-Tibet plateau, one of the region's highest risk areas for human plague, Himalayan marmots are the primary carriers of the infectious bacterium Y. pestis. Y. pestis infection can be transmitted to humans and ...

Autoimmunity plays role in development of COPD, study finds

August 16, 2018
Autoimmunity plays a role in the development of chronic obstructive pulmonary disease (COPD), according to a study led by Georgia State University and Vanderbilt University Medical Center that analyzed human genome information ...

Reliable point-of-care blood test can help prevent toxoplasmosis

August 16, 2018
A recent study, performed in Chicago and Rabat, Morocco, found that a novel finger-prick test for infection with the parasite Toxoplasma gondii during pregnancy—and many other potential applications—is 100 percent sensitive ...

Scientists identify nearly 200 potential tuberculosis drug targets

August 16, 2018
Tuberculosis is one of the top 10 causes of death worldwide. Nearly 2 million people die every year from this infectious disease, and an estimated 2 billion people are chronically infected. The only vaccine, developed almost ...

First mouse model to mimic lung disease could speed discovery of more effective treatments

August 16, 2018
The biggest hurdle to finding effective therapies for idiopathic pulmonary fibrosis (IPF) – a life-threatening condition in which the lungs become scarred and breathing is increasingly difficult – has been the inability ...

Anticancer drug offers potential alternative to transplant for patients with liver failure

August 15, 2018
Patients suffering sudden liver failure could in the future benefit from a new treatment that could reduce the need for transplants, research published today shows.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.