Immune Response Characterization after Controlled Infection with Lyophilized <named-content content-type="genus-species">Shigella sonnei</named-content> 53G

ABSTRACT Shigella is a major cause of moderate to severe diarrhea largely affecting children (<5 years old) living in low- and middle-income countries. Several vaccine candidates are in development, and controlled human infection models (CHIMs) can be useful tools to provide an early assessment o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kristen A. Clarkson, Robert W. Frenck, Michelle Dickey, Akamol E. Suvarnapunya, Lakshmi Chandrasekaran, Hailey P. Weerts, Christopher D. Heaney, Monica McNeal, Kate Detizio, Susan Parker, Amy Hoeper, August L. Bourgeois, Chad K. Porter, Malabi M. Venkatesan, Robert W. Kaminski
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Shigella immunogenicity controlled human infection model antibody immunological memory gut-homing responses Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/41081fd0a38143358a3711b340599c3f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:41081fd0a38143358a3711b340599c3f
record_format	dspace
spelling	oai:doaj.org-article:41081fd0a38143358a3711b340599c3f2021-11-15T15:30:59ZImmune Response Characterization after Controlled Infection with Lyophilized <named-content content-type="genus-species">Shigella sonnei</named-content> 53G10.1128/mSphere.00988-192379-5042https://doaj.org/article/41081fd0a38143358a3711b340599c3f2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00988-19https://doaj.org/toc/2379-5042ABSTRACT Shigella is a major cause of moderate to severe diarrhea largely affecting children (<5 years old) living in low- and middle-income countries. Several vaccine candidates are in development, and controlled human infection models (CHIMs) can be useful tools to provide an early assessment of vaccine efficacy and potentially support licensure. A lyophilized strain of S. sonnei 53G was manufactured and evaluated to establish a dose that safely and reproducibly induced a ≥60% attack rate. Samples were collected pre- and postchallenge to assess intestinal inflammatory responses, antigen-specific serum and mucosal antibody responses, functional antibody responses, and memory B cell responses. Infection with S. sonnei 53G induced a robust intestinal inflammatory response as well as antigen-specific antibodies in serum and mucosal secretions and antigen-specific IgA- and IgG-secreting B cells positive for the α4β7 gut-homing marker. There was no association between clinical disease outcomes and systemic or functional antibody responses postchallenge; however, higher lipopolysaccharide (LPS)-specific serum IgA- and IgA-secreting memory B cell responses were associated with a reduced risk of disease postchallenge. This study provides unique insights into the immune responses pre- and postinfection with S. sonnei 53G in a CHIM, which could help guide the rational design of future vaccines to induce protective immune responses more analogous to those triggered by infection. IMPORTANCE Correlate(s) of immunity have yet to be defined for shigellosis. As previous disease protects against subsequent infection in a serotype-specific manner, investigating immune response profiles pre- and postinfection provides an opportunity to identify immune markers potentially associated with the development of protective immunity and/or with a reduced risk of developing shigellosis postchallenge. This study is the first to report such an extensive characterization of the immune response after challenge with S. sonnei 53G. Results demonstrate an association of progression to shigellosis with robust intestinal inflammatory and mucosal gut-homing responses. An important finding in this study was the association of elevated Shigella LPS-specific serum IgA and memory B cell IgA responses at baseline with reduced risk of disease. The increased baseline IgA responses may contribute to the lack of dose response observed in the study and suggests that IgA responses should be further investigated as potential correlates of immunity.Kristen A. ClarksonRobert W. FrenckMichelle DickeyAkamol E. SuvarnapunyaLakshmi ChandrasekaranHailey P. WeertsChristopher D. HeaneyMonica McNealKate DetizioSusan ParkerAmy HoeperAugust L. BourgeoisChad K. PorterMalabi M. VenkatesanRobert W. KaminskiAmerican Society for MicrobiologyarticleShigellaimmunogenicitycontrolled human infection modelantibodyimmunological memorygut-homing responsesMicrobiologyQR1-502ENmSphere, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Shigella immunogenicity controlled human infection model antibody immunological memory gut-homing responses Microbiology QR1-502
spellingShingle	Shigella immunogenicity controlled human infection model antibody immunological memory gut-homing responses Microbiology QR1-502 Kristen A. Clarkson Robert W. Frenck Michelle Dickey Akamol E. Suvarnapunya Lakshmi Chandrasekaran Hailey P. Weerts Christopher D. Heaney Monica McNeal Kate Detizio Susan Parker Amy Hoeper August L. Bourgeois Chad K. Porter Malabi M. Venkatesan Robert W. Kaminski Immune Response Characterization after Controlled Infection with Lyophilized <named-content content-type="genus-species">Shigella sonnei</named-content> 53G
description	ABSTRACT Shigella is a major cause of moderate to severe diarrhea largely affecting children (<5 years old) living in low- and middle-income countries. Several vaccine candidates are in development, and controlled human infection models (CHIMs) can be useful tools to provide an early assessment of vaccine efficacy and potentially support licensure. A lyophilized strain of S. sonnei 53G was manufactured and evaluated to establish a dose that safely and reproducibly induced a ≥60% attack rate. Samples were collected pre- and postchallenge to assess intestinal inflammatory responses, antigen-specific serum and mucosal antibody responses, functional antibody responses, and memory B cell responses. Infection with S. sonnei 53G induced a robust intestinal inflammatory response as well as antigen-specific antibodies in serum and mucosal secretions and antigen-specific IgA- and IgG-secreting B cells positive for the α4β7 gut-homing marker. There was no association between clinical disease outcomes and systemic or functional antibody responses postchallenge; however, higher lipopolysaccharide (LPS)-specific serum IgA- and IgA-secreting memory B cell responses were associated with a reduced risk of disease postchallenge. This study provides unique insights into the immune responses pre- and postinfection with S. sonnei 53G in a CHIM, which could help guide the rational design of future vaccines to induce protective immune responses more analogous to those triggered by infection. IMPORTANCE Correlate(s) of immunity have yet to be defined for shigellosis. As previous disease protects against subsequent infection in a serotype-specific manner, investigating immune response profiles pre- and postinfection provides an opportunity to identify immune markers potentially associated with the development of protective immunity and/or with a reduced risk of developing shigellosis postchallenge. This study is the first to report such an extensive characterization of the immune response after challenge with S. sonnei 53G. Results demonstrate an association of progression to shigellosis with robust intestinal inflammatory and mucosal gut-homing responses. An important finding in this study was the association of elevated Shigella LPS-specific serum IgA and memory B cell IgA responses at baseline with reduced risk of disease. The increased baseline IgA responses may contribute to the lack of dose response observed in the study and suggests that IgA responses should be further investigated as potential correlates of immunity.
format	article
author	Kristen A. Clarkson Robert W. Frenck Michelle Dickey Akamol E. Suvarnapunya Lakshmi Chandrasekaran Hailey P. Weerts Christopher D. Heaney Monica McNeal Kate Detizio Susan Parker Amy Hoeper August L. Bourgeois Chad K. Porter Malabi M. Venkatesan Robert W. Kaminski
author_facet	Kristen A. Clarkson Robert W. Frenck Michelle Dickey Akamol E. Suvarnapunya Lakshmi Chandrasekaran Hailey P. Weerts Christopher D. Heaney Monica McNeal Kate Detizio Susan Parker Amy Hoeper August L. Bourgeois Chad K. Porter Malabi M. Venkatesan Robert W. Kaminski
author_sort	Kristen A. Clarkson
title	Immune Response Characterization after Controlled Infection with Lyophilized <named-content content-type="genus-species">Shigella sonnei</named-content> 53G
title_short	Immune Response Characterization after Controlled Infection with Lyophilized <named-content content-type="genus-species">Shigella sonnei</named-content> 53G
title_full	Immune Response Characterization after Controlled Infection with Lyophilized <named-content content-type="genus-species">Shigella sonnei</named-content> 53G
title_fullStr	Immune Response Characterization after Controlled Infection with Lyophilized <named-content content-type="genus-species">Shigella sonnei</named-content> 53G
title_full_unstemmed	Immune Response Characterization after Controlled Infection with Lyophilized <named-content content-type="genus-species">Shigella sonnei</named-content> 53G
title_sort	immune response characterization after controlled infection with lyophilized <named-content content-type="genus-species">shigella sonnei</named-content> 53g
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/41081fd0a38143358a3711b340599c3f
work_keys_str_mv	AT kristenaclarkson immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT robertwfrenck immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT michelledickey immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT akamolesuvarnapunya immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT lakshmichandrasekaran immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT haileypweerts immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT christopherdheaney immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT monicamcneal immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT katedetizio immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT susanparker immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT amyhoeper immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT augustlbourgeois immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT chadkporter immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT malabimvenkatesan immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g AT robertwkaminski immuneresponsecharacterizationaftercontrolledinfectionwithlyophilizednamedcontentcontenttypegenusspeciesshigellasonneinamedcontent53g
_version_	1718427821735411712

Immune Response Characterization after Controlled Infection with Lyophilized <named-content content-type="genus-species">Shigella sonnei</named-content> 53G

Ejemplares similares