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Intestinal microbiome composition associated with rotavirus vaccine efficacy in children
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Gut microbiota composition was similar in both Ghanaian and Dutch infants who responded to the oral live-attenuated rotavirus vaccine, according to study findings published in the Journal of Infectious Diseases.
“Large clinical efficacy studies showed a combined vaccine efficacy against severe rotavirus gastroenteritis ranging from 48% to 64% for both Rotarix (RV1; GlaxoSmithKline) and RotaTeq (RV5; Merck) vaccines in Africa and Asia,” Willem M. de Vos, PhD, an investigator at the laboratory of microbiology at Wageningen University, and colleagues wrote. “Emerging effectiveness data in Africa provides similar estimates of rotavirus vaccine protection.
“This compares to an observed efficacy of 85% to 98% against severe rotavirus in trials in wealthier countries in Latin America and Europe.”
To determine whether an association exists between intestinal microbiome composition and a decreased response to rotavirus vaccination in disadvantaged populations, the researchers conducted a nested, case-controlled observational study to compare pre-vaccinated, fecal microbiome compositions between 6-week-old, matched rotavirus responder and non-responder infant pairs in Ghana. The study included 78 Ghanaian infants enrolled in a previous, separate study. The researchers performed microbiota analysis on fecal samples using the Human Intestinal Tract Chip.
Fecal microbiota results were compared with 154 matched, healthy unvaccinated Dutch infants using Pearson correlation scores.
Analysis showed a correlation in microbiome composition between Ghanaian responders and the Dutch infants (P = .002), and a significant difference between Dutch infants and Ghanaian non-responders (false delivery rate [FDR] = 0.12). However, there was not a significant difference detected between Ghanaian responders and non-responders (P = .87).
Researchers observed that vaccine response paralleled an increase in abundance of S. bovis and a decrease in abundance of Bacteroidetes phylum when comparing Ghanaian responders (FDR = 0.008) and non-responders (FDR = 0.003), and between Dutch infants (FDR = 0.002) and Ghanaian non-responders (FDR = 0.009). This study of Ghanaian infants demonstrates that the pre-vaccination intestinal microbiota differs significantly — on a genus-like, phylum and overall composition level — between rotavirus vaccine responders and non-responders in a rural, low-income setting in sub-Saharan Africa and that these microbiome differences are robustly recapitulated when comparing Dutch infants to non-responders,” the researchers wrote. “Rotavirus vaccine response was positively associated with the Bacilli phylum, specifically bacteria related to Streptococcus bovis.
In a separate editorial, Miren Iturriza-Gómara, MSc, PhD, senior lecturer, and Nigel A. Cunliffe, MBChB, PhD, MRCP, lead researcher in the department of clinical infection, microbiology and immunology, Institute of Infection and Global Health at the University of Liverpool, said that although Harris and colleagues’ study was limited due to an inability to account for potentially confounding environmental and host factors, it found an association between rotavirus vaccine immunogenicity and fecal microbiota composition.
“Harris et al. speculated that the positive association between bacteria related to S. bovis and seroconversion in Ghanaian infants may relate to their potential to be opportunistic pathogens triggering inflammatory responses and, hence, act as adjuvants,” they wrote. “On the other hand, bacteria of the phylum Bacteroidetes were more abundant in the non-responders, and the potential for gut colonization with bacteria possessing LPS to inhibit innate immune signaling and endotoxin tolerance warrants further study.” – by Kate Sherrer
Disclosure: This study was funded in part by PATH (grant no. GAT.1566-00758284-SUB), the Bill & Melinda Gates Foundation and the Netherlands Organization for Scientific Research (Spinoza grant 2008 to WMdV). de Vos reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ financial disclosures. Cunliffe reports research grant support and honoraria from GlaxoSmithKline and Iturriza-Gómara reports research grand support from GlaxoSmithKline and SPMSD.
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