Antibiotic modulation of microbiome boosts rotavirus vaccine immunogenicity

Last Updated: 2018-08-08

By Will Boggs MD

NEW YORK (Reuters Health) - Microbiome modulation using narrow-spectrum antibiotics can improve rotavirus vaccine immunogenicity, according to a proof-of-concept trial.

"We were actually surprised that there were positive findings at all, given that our subjects were adults who had previously been exposed to rotavirus disease and were getting a vaccine designed for unexposed infants," Dr. Vanessa C. Harris from Academic Medical Center, Amsterdam, The Netherlands told Reuters Health by email. "We therefore believe that the higher shedding and boosting in the antibiotic arms are fascinating results and support our hypothesis that microbiome modulation can alter rotavirus vaccine immunogenicity."

Rotavirus vaccine effectiveness is excellent in high-income countries but markedly lower in low-income countries in sub-Saharan Africa and Asia, where most rotavirus-related deaths continue to occur. There is mounting evidence supporting a role for the intestinal microbiome in determining rotavirus vaccine immunogenicity.

Dr. Harris's team investigated the microbiome's role in this setting by altering the microbiota in 66 healthy adults prior to rotavirus vaccination. Twenty-three volunteers received broad-spectrum antibiotics (a positive control expected to deplete most bacterial taxa in the intestine); 21 received narrow-spectrum antibiotics (vancomycin, expected to decrease Bacteroidetes and increase Proteobacteria); and 22 received no antibiotics.

After completion of antibiotic therapy (and a washout period to eliminate antibiotics), all subjects were vaccinated with rotavirus vaccine, pneumococcal vaccine, and tetanus toxoid vaccine.

The primary endpoint - anti-rotavirus IgA geometric mean titers at 28 days - did not change significantly according to treatment group, the authors reported August 8th online in Cell Host & Microbe.

The proportion of subjects who had secondary immune responses (anti-rotavirus IgA boosting), however, was significantly higher in the narrow-spectrum antibiotic group (38%) than in the broad-spectrum group (4.7%) or control group (4.7%).

There was a higher amount and proportion of rotavirus shedding in both antibiotic groups following rotavirus vaccination, compared with controls.

Both antibiotic treatments caused major alterations to overall bacterial community structure and depleted Bacteroidetes, but only vancomycin led to a reduction of Firmicutes and an expansion of Proteobacteria, changes that some studies have shown to correlate with rotavirus vaccine immunogenicity.

Antibiotic therapy did not alter immune responses to the other vaccines.

"We knew that rotavirus vaccine immunogenicity correlated with intestinal microbiome composition in some low-income settings, and we simply wanted to test if large-scale alteration of the intestinal microbiome in humans (in this case via antibiotics) could improve vaccine performance," Dr. Harris said. "This study shows that it can."

"We see this as a starting point," she said. "Now we can go back to the bench and test if individual or groups of bacteria can achieve the same effect. Ideally, we would not give antibiotics to improve rotavirus vaccine performance, but use rationally selected, evidence-based bacteria or bacterial byproducts that could be administered together with the vaccine."

Dr. Harris added, "Rotavirus vaccines have dramatically lowered diarrheal mortality in low- and middle-income countries. However, infants continue to die from diarrheal diseases in these settings. Ensuring that infants get vaccines and improving the vaccines that we currently have therefore requires sustained global attention, research, investment, and effort."

Dr. Edward Parker from Imperial College London, UK, who recently reviewed causes of impaired oral vaccine efficacy in developing countries, told Reuters Health by email, "Overall, microbiota manipulation had a limited effect on rotavirus vaccine response. However, the vaccine virus appeared to replicate more efficiently in antibiotic recipients, potentially due to the changes in microbiota composition in these individuals."

"We currently lack a clear understanding of the impact of microbiota composition on rotavirus vaccine response," he said. "Meanwhile, our tools for manipulating the microbiome remain blunt. Both of these issues must be rectified if we are to improve vaccine effectiveness by targeting the gut microbiota."

Dr. Miren Iturriza-Gomara from University of Liverpool, UK, who co-authored the review with Dr. Parker and recently evaluated the impact of intestinal microbiota on the immunogenicity of oral rotavirus vaccine given to infants in India, says the new study adds little to what was already known and "has not produced any leads for a practicable public health intervention."

In particular, she told Reuters Health in an email, the findings provide "no evidence to support the indiscriminate use of antibiotics in the hope they may improve responses to rotavirus vaccine."

SOURCE: http://bit.ly/2Oll8OQ and http://bit.ly/2OiQR39

Cell Host & Microbe 2018.