A Novel <italic toggle="yes">Shigella</italic> Proteome Microarray Discriminates Targets of Human Antibody Reactivity following Oral Vaccination and Experimental Challenge

ABSTRACT Shigella spp. are a major cause of diarrhea and dysentery in children under 5 years old in the developing world. The development of an effective vaccine remains a public health priority, necessitating improved understanding of immune responses to Shigella and identification of protective an...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Esther Ndungo, Arlo Randall, Tracy H. Hazen, Dane A. Kania, Krista Trappl-Kimmons, Xiaowu Liang, Eileen M. Barry, Karen L. Kotloff, Subhra Chakraborty, Sachin Mani, David A. Rasko, Marcela F. Pasetti
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Shigella antibodies proteome microarray vaccines Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7be8f586ee784834878974c3c19d46a9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7be8f586ee784834878974c3c19d46a9
record_format	dspace
spelling	oai:doaj.org-article:7be8f586ee784834878974c3c19d46a92021-11-15T15:25:50ZA Novel <italic toggle="yes">Shigella</italic> Proteome Microarray Discriminates Targets of Human Antibody Reactivity following Oral Vaccination and Experimental Challenge10.1128/mSphere.00260-182379-5042https://doaj.org/article/7be8f586ee784834878974c3c19d46a92018-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00260-18https://doaj.org/toc/2379-5042ABSTRACT Shigella spp. are a major cause of diarrhea and dysentery in children under 5 years old in the developing world. The development of an effective vaccine remains a public health priority, necessitating improved understanding of immune responses to Shigella and identification of protective antigens. We report the development of a core Shigella proteome microarray consisting of 2,133 antigen targets common to all Shigella species. We evaluated the microarray with serum samples from volunteers immunized with either an inactivated whole-cell S. flexneri serotype 2a (Sf2aWC) vaccine or a live attenuated S. flexneri 2a vaccine strain (CVD 1204) or challenged with wild-type S. flexneri 2a (Sf2a challenge). Baseline reactivities to most antigens were detected postintervention in all three groups. Similar immune profiles were observed after CVD 1204 vaccination and Sf2a challenge. Antigens with the largest increases in mean reactivity postintervention were members of the type three secretion system (T3SS), some of which are regarded as promising vaccine targets: these are the invasion plasmid antigens (Ipas) IpaB, IpaC, and IpaD. In addition, new immunogenic targets (IpaA, IpaH, and SepA) were identified. Importantly, immunoreactivities to antigens in the microarray correlated well with antibody titers determined by enzyme-linked immunosorbent assay (ELISA), validating the use of the microarray platform. Finally, our analysis uncovered an immune signature consisting of three conserved proteins (IpaA, IpaB, and IpaC) that was predictive of protection against shigellosis. In conclusion, the Shigella proteome microarray is a robust platform for interrogating serological reactivity to multiple antigens at once and identifying novel targets for the development of broadly protective vaccines. IMPORTANCE Each year, more than 180 million cases of severe diarrhea caused by Shigella occur globally. Those affected (mostly children in poor regions) experience long-term sequelae that severely impair quality of life. Without a licensed vaccine, the burden of disease represents a daunting challenge. An improved understanding of immune responses to Shigella is necessary to support ongoing efforts to identify a safe and effective vaccine. We developed a microarray containing >2,000 proteins common to all Shigella species. Using sera from human adults who received a killed whole-cell or live attenuated vaccine or were experimentally challenged with virulent organisms, we identified new immune-reactive antigens and defined a T3SS protein signature associated with clinical protection.Esther NdungoArlo RandallTracy H. HazenDane A. KaniaKrista Trappl-KimmonsXiaowu LiangEileen M. BarryKaren L. KotloffSubhra ChakrabortySachin ManiDavid A. RaskoMarcela F. PasettiAmerican Society for MicrobiologyarticleShigellaantibodiesproteome microarrayvaccinesMicrobiologyQR1-502ENmSphere, Vol 3, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Shigella antibodies proteome microarray vaccines Microbiology QR1-502
spellingShingle	Shigella antibodies proteome microarray vaccines Microbiology QR1-502 Esther Ndungo Arlo Randall Tracy H. Hazen Dane A. Kania Krista Trappl-Kimmons Xiaowu Liang Eileen M. Barry Karen L. Kotloff Subhra Chakraborty Sachin Mani David A. Rasko Marcela F. Pasetti A Novel <italic toggle="yes">Shigella</italic> Proteome Microarray Discriminates Targets of Human Antibody Reactivity following Oral Vaccination and Experimental Challenge
description	ABSTRACT Shigella spp. are a major cause of diarrhea and dysentery in children under 5 years old in the developing world. The development of an effective vaccine remains a public health priority, necessitating improved understanding of immune responses to Shigella and identification of protective antigens. We report the development of a core Shigella proteome microarray consisting of 2,133 antigen targets common to all Shigella species. We evaluated the microarray with serum samples from volunteers immunized with either an inactivated whole-cell S. flexneri serotype 2a (Sf2aWC) vaccine or a live attenuated S. flexneri 2a vaccine strain (CVD 1204) or challenged with wild-type S. flexneri 2a (Sf2a challenge). Baseline reactivities to most antigens were detected postintervention in all three groups. Similar immune profiles were observed after CVD 1204 vaccination and Sf2a challenge. Antigens with the largest increases in mean reactivity postintervention were members of the type three secretion system (T3SS), some of which are regarded as promising vaccine targets: these are the invasion plasmid antigens (Ipas) IpaB, IpaC, and IpaD. In addition, new immunogenic targets (IpaA, IpaH, and SepA) were identified. Importantly, immunoreactivities to antigens in the microarray correlated well with antibody titers determined by enzyme-linked immunosorbent assay (ELISA), validating the use of the microarray platform. Finally, our analysis uncovered an immune signature consisting of three conserved proteins (IpaA, IpaB, and IpaC) that was predictive of protection against shigellosis. In conclusion, the Shigella proteome microarray is a robust platform for interrogating serological reactivity to multiple antigens at once and identifying novel targets for the development of broadly protective vaccines. IMPORTANCE Each year, more than 180 million cases of severe diarrhea caused by Shigella occur globally. Those affected (mostly children in poor regions) experience long-term sequelae that severely impair quality of life. Without a licensed vaccine, the burden of disease represents a daunting challenge. An improved understanding of immune responses to Shigella is necessary to support ongoing efforts to identify a safe and effective vaccine. We developed a microarray containing >2,000 proteins common to all Shigella species. Using sera from human adults who received a killed whole-cell or live attenuated vaccine or were experimentally challenged with virulent organisms, we identified new immune-reactive antigens and defined a T3SS protein signature associated with clinical protection.
format	article
author	Esther Ndungo Arlo Randall Tracy H. Hazen Dane A. Kania Krista Trappl-Kimmons Xiaowu Liang Eileen M. Barry Karen L. Kotloff Subhra Chakraborty Sachin Mani David A. Rasko Marcela F. Pasetti
author_facet	Esther Ndungo Arlo Randall Tracy H. Hazen Dane A. Kania Krista Trappl-Kimmons Xiaowu Liang Eileen M. Barry Karen L. Kotloff Subhra Chakraborty Sachin Mani David A. Rasko Marcela F. Pasetti
author_sort	Esther Ndungo
title	A Novel <italic toggle="yes">Shigella</italic> Proteome Microarray Discriminates Targets of Human Antibody Reactivity following Oral Vaccination and Experimental Challenge
title_short	A Novel <italic toggle="yes">Shigella</italic> Proteome Microarray Discriminates Targets of Human Antibody Reactivity following Oral Vaccination and Experimental Challenge
title_full	A Novel <italic toggle="yes">Shigella</italic> Proteome Microarray Discriminates Targets of Human Antibody Reactivity following Oral Vaccination and Experimental Challenge
title_fullStr	A Novel <italic toggle="yes">Shigella</italic> Proteome Microarray Discriminates Targets of Human Antibody Reactivity following Oral Vaccination and Experimental Challenge
title_full_unstemmed	A Novel <italic toggle="yes">Shigella</italic> Proteome Microarray Discriminates Targets of Human Antibody Reactivity following Oral Vaccination and Experimental Challenge
title_sort	novel <italic toggle="yes">shigella</italic> proteome microarray discriminates targets of human antibody reactivity following oral vaccination and experimental challenge
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/7be8f586ee784834878974c3c19d46a9
work_keys_str_mv	AT estherndungo anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT arlorandall anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT tracyhhazen anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT daneakania anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT kristatrapplkimmons anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT xiaowuliang anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT eileenmbarry anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT karenlkotloff anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT subhrachakraborty anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT sachinmani anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT davidarasko anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT marcelafpasetti anovelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT estherndungo novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT arlorandall novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT tracyhhazen novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT daneakania novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT kristatrapplkimmons novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT xiaowuliang novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT eileenmbarry novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT karenlkotloff novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT subhrachakraborty novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT sachinmani novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT davidarasko novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge AT marcelafpasetti novelitalictoggleyesshigellaitalicproteomemicroarraydiscriminatestargetsofhumanantibodyreactivityfollowingoralvaccinationandexperimentalchallenge
_version_	1718427958449799168

A Novel <italic toggle="yes">Shigella</italic> Proteome Microarray Discriminates Targets of Human Antibody Reactivity following Oral Vaccination and Experimental Challenge

Ejemplares similares