Nasopharynx Microbiome and Vaccination in Children
The nasopharynx (NP) is home to many microorganisms that begin colonizing the body soon after birth. The collection of microbes, the microbiome, provides protection against pathogens, confers metabolic capabilities that humans lack, as well as other functions, and interacts extensively with the human host without provoking host defense responses. Microbes from the NP can cause diseases, such as pneumonia or meningitis, depending on which nearby tissues they invade. Normally these organisms do not cause disease, possibly because the complex ecosystem of the microbiome has evolved over millions of years to keep organisms mutually in check. Little is known about the detailed structure of the NP microbiome, especially in newborns and during early life as the microbiome is formed. Understanding how the microbiome is formed, what contributions come from parents, siblings, or caregivers, and how different geographical environments influence the NP microbiome is an important task of metagenomic research. Knowledge of these phenomena would allow abnormal situations to be recognized, offering the opportunity to prevent disease and ensure healthy development of the infant.
Vaccination is likely to have important consequences for the NP microbiome. Current pneumococcal vaccines are directed against multiple serotypes thus potentially eliminating these from the microbiome. Based on observations on this and other vaccines, new organisms are expected to move into the empty niches created by vaccine elimination of organisms. Thus the structure of the microbiome is altered by vaccines. The unintended consequences of this alteration remain to be seen. The aim of this exploratory study is to define the NP microbiome in newborns by sampling their NP monthly in the first year of life and analyzing these specimens with metagenomic DNA sequencing techniques. This analysis will reveal the organisms that comprise the microbiome, their abundances, and how their relative abundance changes over time. We will also collect a rich set of clinical data about the children and correlate the (changing) structure of the microbiome with the infants' health. These studies will be performed at four sites: Bangladesh, where the national vaccination program does not include pneumococcal conjugate vaccine (PCV); the Philippines where there is also no PCV in the national program but where half the children enrolled in the study will be given PCV; and two sites in Africa (The Gambia and South Africa) which both have already included PCV in their national programs and all children will be PCV-vaccinated. This range in geography and vaccine status will allow observations on the effects on the NP microbiome and the impact of this on infant health.
The results obtained from this study will lead to a better understanding of the consequences (side effects) of vaccination against pneumococci. Moreover, the metagenomic approach taken in this study naturally lends itself as a diagnostic. Future research could lead to the development of a tool to identify children at risk for disease because of an altered NP microbiome. Finally, the definition of the healthy NP microbiome and the at-risk microbiome that this study will yield also suggest that treatment of at-risk children with probiotics could reduce the possibility of disease.
Bill and Melinda Gates Foundation
Research Institute for Tropical Medicine (RITM), Muntinlupa City, The Phillipines
Site Principal Investigator:
Site JCVI Advisor:
Hanna Nohynek, Professor of International Health, National Institute of Health and Welfare, Finland
Respiratory and Meningeal Pathogens Research Unit (RMPRU), Soweto, South Africa
Site Principal Investigator:
Site Co-Principal Investigator:
Keith Klugman, Foeg Professor of Global Health, Emory University, Atlanta, GA