Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes

Rasmus Mortensen; Dennis Christensen; Lasse Bøllehuus Hansen; Jan Pravsgaard Christensen; Peter Andersen; Jes Dietrich

doi:10.1371/journal.pone.0175707

Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes

Rasmus Mortensen, Dennis Christensen, Lasse Bøllehuus Hansen, Jan Pravsgaard Christensen, Peter Andersen, Jes Dietrich^*

^*Corresponding author for this work

15 Citations (Scopus)

128 Downloads (Pure)

Abstract

Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

Original language	English
Article number	e0175707
Journal	PLOS ONE
Volume	12
Issue number	4
Number of pages	17
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0175707
Publication status	Published - Apr 2017

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Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenesFinal published version, 2 MBLicence: CC BY

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title = "Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes",

abstract = "Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.",

author = "Rasmus Mortensen and Dennis Christensen and Hansen, {Lasse B{\o}llehuus} and Christensen, {Jan Pravsgaard} and Peter Andersen and Jes Dietrich",

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T1 - Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes

AU - Mortensen, Rasmus

AU - Christensen, Dennis

AU - Hansen, Lasse Bøllehuus

AU - Christensen, Jan Pravsgaard

AU - Andersen, Peter

AU - Dietrich, Jes

PY - 2017/4

Y1 - 2017/4

N2 - Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

AB - Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

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SN - 1932-6203

VL - 12

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 4

M1 - e0175707

ER -

Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes

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