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Editor's Pick Research Article

Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice

Michael J. Mina, Jonathan A. McCullers, Keith P. Klugman
Larry S. McDaniel, Editor
Michael J. Mina
aMedical Scientist Training Program, Emory University School of Medicine, Atlanta, Georgia, USA
bHubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
cDepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
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Jonathan A. McCullers
cDepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
dDepartment of Pediatrics, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
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Keith P. Klugman
bHubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
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Larry S. McDaniel
University of Mississippi Medical Center
Roles: Editor
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DOI: 10.1128/mBio.01040-13
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ABSTRACT

Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection.

IMPORTANCE Following infection with an influenza virus, infected or recently recovered individuals become transiently susceptible to excess bacterial infections, particularly Streptococcus pneumoniae and Staphylococcus aureus. Indeed, in the absence of preexisting comorbidities, bacterial infections are a leading cause of severe disease during influenza epidemics. While this synergy has been known and is well studied, what has not been explored is the natural extension of these interactions to live attenuated influenza vaccines (LAIVs). Here we show, in mice, that vaccination with LAIV primes the upper respiratory tract for increased bacterial growth and persistence of bacterial carriage, in a manner nearly identical to that seen following wild-type influenza virus infections. Importantly, LAIV, unlike wild-type virus, did not increase severe bacterial disease of the lower respiratory tract. These findings may have consequences for individual bacterial disease processes within the upper respiratory tract, as well as bacterial transmission dynamics within LAIV-vaccinated populations

  • Copyright © 2014 Mina et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice
Michael J. Mina, Jonathan A. McCullers, Keith P. Klugman
mBio Feb 2014, 5 (1) e01040-13; DOI: 10.1128/mBio.01040-13

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Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice
Michael J. Mina, Jonathan A. McCullers, Keith P. Klugman
mBio Feb 2014, 5 (1) e01040-13; DOI: 10.1128/mBio.01040-13
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