Attenuated strain of CVB3 with a mutation in the CAR-interacting region protects against both myocarditis and pancreatitis

Abstract Coxsackievirus B3 (CVB3), is commonly implicated in myocarditis, which can lead to dilated cardiomyopathy, in addition to causing acute pancreatitis and meningitis. Yet, no vaccines are currently available to prevent this infection. Here, we describe the derivation of a live attenuated vacc...

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Autores principales:	Ninaad Lasrado, Arunakumar Gangaplara, Chandirasegaran Massilamany, Rajkumar Arumugam, Allison Shelbourn, Mahima T. Rasquinha, Rakesh H. Basavalingappa, Gustavo Delhon, Shi-Hua Xiang, Asit K. Pattnaik, David Steffen, Jay Reddy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a4c70442348c476e871597050323e742
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spelling	oai:doaj.org-article:a4c70442348c476e871597050323e7422021-12-02T17:41:26ZAttenuated strain of CVB3 with a mutation in the CAR-interacting region protects against both myocarditis and pancreatitis10.1038/s41598-021-90434-w2045-2322https://doaj.org/article/a4c70442348c476e871597050323e7422021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90434-whttps://doaj.org/toc/2045-2322Abstract Coxsackievirus B3 (CVB3), is commonly implicated in myocarditis, which can lead to dilated cardiomyopathy, in addition to causing acute pancreatitis and meningitis. Yet, no vaccines are currently available to prevent this infection. Here, we describe the derivation of a live attenuated vaccine virus, termed mutant (Mt) 10, encoding a single amino acid substitution H790A within the viral protein 1, that prevents CVB3 infection in mice and protects from both myocarditis and pancreatitis in challenge studies. We noted that animals vaccinated with Mt 10 developed virus-neutralizing antibodies, predominantly containing IgG2a and IgG2b, and to a lesser extent IgG3 and IgG1. Furthermore, by using major histocompatibility complex class II dextramers and tetramers, we demonstrated that Mt 10 induces antigen-specific T cell responses that preferentially produce interferon-γ. Finally, neither vaccine recipients nor those challenged with the wild-type virus revealed evidence of autoimmunity or cardiac injury as determined by T cell response to cardiac myosin and measurement of circulating cardiac troponin I levels, respectively. Together, our data suggest that Mt 10 is a vaccine candidate that prevents CVB3 infection through the induction of neutralizing antibodies and antigen-specific T cell responses, the two critical components needed for complete protection against virus infections in vaccine studies.Ninaad LasradoArunakumar GangaplaraChandirasegaran MassilamanyRajkumar ArumugamAllison ShelbournMahima T. RasquinhaRakesh H. BasavalingappaGustavo DelhonShi-Hua XiangAsit K. PattnaikDavid SteffenJay ReddyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ninaad Lasrado Arunakumar Gangaplara Chandirasegaran Massilamany Rajkumar Arumugam Allison Shelbourn Mahima T. Rasquinha Rakesh H. Basavalingappa Gustavo Delhon Shi-Hua Xiang Asit K. Pattnaik David Steffen Jay Reddy Attenuated strain of CVB3 with a mutation in the CAR-interacting region protects against both myocarditis and pancreatitis
description	Abstract Coxsackievirus B3 (CVB3), is commonly implicated in myocarditis, which can lead to dilated cardiomyopathy, in addition to causing acute pancreatitis and meningitis. Yet, no vaccines are currently available to prevent this infection. Here, we describe the derivation of a live attenuated vaccine virus, termed mutant (Mt) 10, encoding a single amino acid substitution H790A within the viral protein 1, that prevents CVB3 infection in mice and protects from both myocarditis and pancreatitis in challenge studies. We noted that animals vaccinated with Mt 10 developed virus-neutralizing antibodies, predominantly containing IgG2a and IgG2b, and to a lesser extent IgG3 and IgG1. Furthermore, by using major histocompatibility complex class II dextramers and tetramers, we demonstrated that Mt 10 induces antigen-specific T cell responses that preferentially produce interferon-γ. Finally, neither vaccine recipients nor those challenged with the wild-type virus revealed evidence of autoimmunity or cardiac injury as determined by T cell response to cardiac myosin and measurement of circulating cardiac troponin I levels, respectively. Together, our data suggest that Mt 10 is a vaccine candidate that prevents CVB3 infection through the induction of neutralizing antibodies and antigen-specific T cell responses, the two critical components needed for complete protection against virus infections in vaccine studies.
format	article
author	Ninaad Lasrado Arunakumar Gangaplara Chandirasegaran Massilamany Rajkumar Arumugam Allison Shelbourn Mahima T. Rasquinha Rakesh H. Basavalingappa Gustavo Delhon Shi-Hua Xiang Asit K. Pattnaik David Steffen Jay Reddy
author_facet	Ninaad Lasrado Arunakumar Gangaplara Chandirasegaran Massilamany Rajkumar Arumugam Allison Shelbourn Mahima T. Rasquinha Rakesh H. Basavalingappa Gustavo Delhon Shi-Hua Xiang Asit K. Pattnaik David Steffen Jay Reddy
author_sort	Ninaad Lasrado
title	Attenuated strain of CVB3 with a mutation in the CAR-interacting region protects against both myocarditis and pancreatitis
title_short	Attenuated strain of CVB3 with a mutation in the CAR-interacting region protects against both myocarditis and pancreatitis
title_full	Attenuated strain of CVB3 with a mutation in the CAR-interacting region protects against both myocarditis and pancreatitis
title_fullStr	Attenuated strain of CVB3 with a mutation in the CAR-interacting region protects against both myocarditis and pancreatitis
title_full_unstemmed	Attenuated strain of CVB3 with a mutation in the CAR-interacting region protects against both myocarditis and pancreatitis
title_sort	attenuated strain of cvb3 with a mutation in the car-interacting region protects against both myocarditis and pancreatitis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a4c70442348c476e871597050323e742
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Attenuated strain of CVB3 with a mutation in the CAR-interacting region protects against both myocarditis and pancreatitis

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