The intestinal microbiota could increase rotavirus vaccine effectiveness

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Preliminary results suggest that targeted changes in the intestinal microbiota could improve rotavirus vaccine immunogenicity, which is decreasing in developing countries where prevalence of this disease is highest.

 

Rotavirus vaccination, although effective in Western countries, is much less so in sub-Saharan Africa and Asia, where the number of fatal childhood diarrheas caused by severe gastroenteritis still runs into tens of thousands. The intestinal microbiota could be involved in this phenomenon: a lower rate of Gammaproteobacteria and a higher rate of Bacteroidetes seem to be associated with poor vaccine immunogenicity. Since the effect of vancomycin is precisely to reverse these two variations of bacterial populations, a team of Dutch and American researchers have studied the effects of an adjuvant antibiotic therapy.

Improved response with the addition of vancomycin

For a period of 16 months, a cohort composed of 63 Dutch adults was monitored. They were divided in three groups: the first group received a 7-day treatment with vancomycin, the second received a 7-day treatment with broad spectrum antibiotics (vancomycin, ciprofloxacin and metronidazole), and the last received no antibiotics. They were then all vaccinated 36 hours after the antibiotic treatment with one of the two rotavirus vaccines available on the market, and the immune response was assessed based on the blood level of IgA and the amount of antigens excreted in stools. IgA levels were high in all subjects at baseline. A slight peak of IgA on Day 7 was observed in 38% of volunteers in the vancomycin group. More importantly, the fecal excretion of rotavirus antigens was more pronounced in that same group. According to the scientists, it seems that vancomycin indeed induced an increased immune reaction after vaccination.

Immunomodulatory bacterial components

At the microbiotic level, and independently of the type of antibiotics used, the vaccine immunogenicity was associated to an increase in Enterobacteriaceae (belonging to the Proteobacteria group) and a decrease in Prevotellaceae (belonging to the Bacteroidetes group). According to the authors, virions could be stabilized by bacterial lipopolysaccharides (LPS), which would promote their reproduction–and thus a stronger immune reaction. Moreover, the structure of LPS produced by Proteobacteria tends to stimulate cytokines, contrary to that of Bacteroidetes. More generally, antibiotics could act by reducing the number of bacteria promoting immune tolerance and/or increasing the proportion of bacteria promoting intestinal mucosal immunity.

Alternatives to adjuvant antibiotic treatment

However, these results should be put into perspective: the population included in the study (Caucasian adults who had already been exposed to the rotavirus) is different from the one targeted by rotavirus vaccination (seronegative infants*). But if they came to be confirmed, these first findings would not result in the use of vancomycin as an adjuvant therapy to vaccination–too expensive and iatrogenic–but in the use of probiotics, or even targeting of metabolites or bacterial cellular components promoting viral replication that could lead to a better vaccine immunogenicity.

 

* Rotavirus-associated gastroenteritis mainly occur in children aged between 6 months and 2 years

 

Sources:

Harris VC et al. Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial. Cell Host Microbe, 2018 Aug 8;24(2):197-207.e4

Evans AS. Viral Infections of Humans: Epidemiology and Control. Springer Science & Business Media, 11 nov. 2013