Vaccine Protection against Multidrug-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection

ABSTRACT Klebsiella pneumoniae is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by K. pneumoniae is often compounded by multidrug resistance—a potential problem for individuals with significant comorbidities or other risk fa...

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Autores principales:	Natalia Malachowa, Scott D. Kobayashi, Adeline R. Porter, Brett Freedman, Patrick W. Hanley, Jamie Lovaglio, Greg A. Saturday, Donald J. Gardner, Dana P. Scott, Amanda Griffin, Kathleen Cordova, Dan Long, Rebecca Rosenke, Daniel E. Sturdevant, Daniel Bruno, Craig Martens, Barry N. Kreiswirth, Frank R. DeLeo
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	antibiotic resistance capsule polysaccharide bactericidal activity nonhuman primate pneumonia vaccine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/72d9814a0b744c26aa2313fd1a806127
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spelling	oai:doaj.org-article:72d9814a0b744c26aa2313fd1a8061272021-11-15T15:54:47ZVaccine Protection against Multidrug-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection10.1128/mBio.02994-192150-7511https://doaj.org/article/72d9814a0b744c26aa2313fd1a8061272019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02994-19https://doaj.org/toc/2150-7511ABSTRACT Klebsiella pneumoniae is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by K. pneumoniae is often compounded by multidrug resistance—a potential problem for individuals with significant comorbidities or other risk factors for infection. A carbapenem-resistant K. pneumoniae strain classified as multilocus sequence type 258 (ST258) is widespread in the United States and is usually multidrug resistant. Thus, treatment of ST258 infections is often difficult. Inasmuch as new preventive and/or therapeutic measures are needed for treatment of such infections, we developed an ST258 pneumonia model in cynomolgus macaques and tested the ability of an ST258 capsule polysaccharide type 2 (CPS2) vaccine to moderate disease severity. Compared with sham-vaccinated animals, those vaccinated with ST258 CPS2 had significantly less disease as assessed by radiography 24 h after intrabronchial installation of 108 CFU of ST258. All macaques vaccinated with CPS2 ultimately developed ST258-specific antibodies that significantly enhanced serum bactericidal activity and killing of ST258 by macaque neutrophils ex vivo. Consistent with a protective immune response to CPS2, transcripts encoding inflammatory mediators were increased in infected lung tissues obtained from CPS-vaccinated animals compared with control, sham-vaccinated macaques. Taken together, our data provide support for the idea that vaccination with ST258 CPS can be used to prevent or moderate infections caused by ST258. As with studies performed decades earlier, we propose that this prime-boost vaccination approach can be extended to include multiple capsule types. IMPORTANCE Multidrug-resistant bacteria continue to be a major problem worldwide, especially among individuals with significant comorbidities and other risk factors for infection. K. pneumoniae is among the leading causes of health care-associated infections, and the organism is often resistant to multiple classes of antibiotics. A carbapenem-resistant K. pneumoniae strain known as multilocus sequence type 258 (ST258) is the predominant carbapenem-resistant Enterobacteriaceae in the health care setting in the United States. Infections caused by ST258 are often difficult to treat and new prophylactic measures and therapeutic approaches are needed. To that end, we developed a lower respiratory tract infection model in cynomolgus macaques in which to test the ability of ST258 CPS to protect against severe ST258 infection.Natalia MalachowaScott D. KobayashiAdeline R. PorterBrett FreedmanPatrick W. HanleyJamie LovaglioGreg A. SaturdayDonald J. GardnerDana P. ScottAmanda GriffinKathleen CordovaDan LongRebecca RosenkeDaniel E. SturdevantDaniel BrunoCraig MartensBarry N. KreiswirthFrank R. DeLeoAmerican Society for Microbiologyarticleantibiotic resistancecapsule polysaccharidebactericidal activitynonhuman primatepneumoniavaccineMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotic resistance capsule polysaccharide bactericidal activity nonhuman primate pneumonia vaccine Microbiology QR1-502
spellingShingle	antibiotic resistance capsule polysaccharide bactericidal activity nonhuman primate pneumonia vaccine Microbiology QR1-502 Natalia Malachowa Scott D. Kobayashi Adeline R. Porter Brett Freedman Patrick W. Hanley Jamie Lovaglio Greg A. Saturday Donald J. Gardner Dana P. Scott Amanda Griffin Kathleen Cordova Dan Long Rebecca Rosenke Daniel E. Sturdevant Daniel Bruno Craig Martens Barry N. Kreiswirth Frank R. DeLeo Vaccine Protection against Multidrug-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection
description	ABSTRACT Klebsiella pneumoniae is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by K. pneumoniae is often compounded by multidrug resistance—a potential problem for individuals with significant comorbidities or other risk factors for infection. A carbapenem-resistant K. pneumoniae strain classified as multilocus sequence type 258 (ST258) is widespread in the United States and is usually multidrug resistant. Thus, treatment of ST258 infections is often difficult. Inasmuch as new preventive and/or therapeutic measures are needed for treatment of such infections, we developed an ST258 pneumonia model in cynomolgus macaques and tested the ability of an ST258 capsule polysaccharide type 2 (CPS2) vaccine to moderate disease severity. Compared with sham-vaccinated animals, those vaccinated with ST258 CPS2 had significantly less disease as assessed by radiography 24 h after intrabronchial installation of 108 CFU of ST258. All macaques vaccinated with CPS2 ultimately developed ST258-specific antibodies that significantly enhanced serum bactericidal activity and killing of ST258 by macaque neutrophils ex vivo. Consistent with a protective immune response to CPS2, transcripts encoding inflammatory mediators were increased in infected lung tissues obtained from CPS-vaccinated animals compared with control, sham-vaccinated macaques. Taken together, our data provide support for the idea that vaccination with ST258 CPS can be used to prevent or moderate infections caused by ST258. As with studies performed decades earlier, we propose that this prime-boost vaccination approach can be extended to include multiple capsule types. IMPORTANCE Multidrug-resistant bacteria continue to be a major problem worldwide, especially among individuals with significant comorbidities and other risk factors for infection. K. pneumoniae is among the leading causes of health care-associated infections, and the organism is often resistant to multiple classes of antibiotics. A carbapenem-resistant K. pneumoniae strain known as multilocus sequence type 258 (ST258) is the predominant carbapenem-resistant Enterobacteriaceae in the health care setting in the United States. Infections caused by ST258 are often difficult to treat and new prophylactic measures and therapeutic approaches are needed. To that end, we developed a lower respiratory tract infection model in cynomolgus macaques in which to test the ability of ST258 CPS to protect against severe ST258 infection.
format	article
author	Natalia Malachowa Scott D. Kobayashi Adeline R. Porter Brett Freedman Patrick W. Hanley Jamie Lovaglio Greg A. Saturday Donald J. Gardner Dana P. Scott Amanda Griffin Kathleen Cordova Dan Long Rebecca Rosenke Daniel E. Sturdevant Daniel Bruno Craig Martens Barry N. Kreiswirth Frank R. DeLeo
author_facet	Natalia Malachowa Scott D. Kobayashi Adeline R. Porter Brett Freedman Patrick W. Hanley Jamie Lovaglio Greg A. Saturday Donald J. Gardner Dana P. Scott Amanda Griffin Kathleen Cordova Dan Long Rebecca Rosenke Daniel E. Sturdevant Daniel Bruno Craig Martens Barry N. Kreiswirth Frank R. DeLeo
author_sort	Natalia Malachowa
title	Vaccine Protection against Multidrug-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection
title_short	Vaccine Protection against Multidrug-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection
title_full	Vaccine Protection against Multidrug-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection
title_fullStr	Vaccine Protection against Multidrug-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection
title_full_unstemmed	Vaccine Protection against Multidrug-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection
title_sort	vaccine protection against multidrug-resistant <named-content content-type="genus-species">klebsiella pneumoniae</named-content> in a nonhuman primate model of severe lower respiratory tract infection
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/72d9814a0b744c26aa2313fd1a806127
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Vaccine Protection against Multidrug-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection

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