Biochemical characterization and evaluation of a Brugia malayi small heat shock protein as a vaccine against lymphatic filariasis.

Filarial nematodes enjoy one of the longest life spans of any human pathogen due to effective immune evasion strategies developed by the parasite. Among the various immune evasion strategies exhibited by the parasite, Interleukin 10 (IL-10) productions and IL-10 mediated immune suppression has signi...

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Autores principales:	Gajalakshmi Dakshinamoorthy, Abhilash Kumble Samykutty, Gnanasekar Munirathinam, Gangadhar Bhaurao Shinde, Thomas Nutman, Maryada Venkatarami Reddy, Ramaswamy Kalyanasundaram
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe05230b84d34207889cb379f50ef787
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spelling	oai:doaj.org-article:fe05230b84d34207889cb379f50ef7872021-11-18T07:23:08ZBiochemical characterization and evaluation of a Brugia malayi small heat shock protein as a vaccine against lymphatic filariasis.1932-620310.1371/journal.pone.0034077https://doaj.org/article/fe05230b84d34207889cb379f50ef7872012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22496777/?tool=EBIhttps://doaj.org/toc/1932-6203Filarial nematodes enjoy one of the longest life spans of any human pathogen due to effective immune evasion strategies developed by the parasite. Among the various immune evasion strategies exhibited by the parasite, Interleukin 10 (IL-10) productions and IL-10 mediated immune suppression has significant negative impact on the host immune system. Recently, we identified a small heat shock protein expressed by Brugia malayi (BmHsp12.6) that can bind to soluble human IL-10 receptor alpha (IL-10R) and activate IL-10 mediated effects in cell lines. In this study we show that the IL-10R binding region of BmHsp12.6 is localized to its N-terminal region. This region has significant sequence similarity to the receptor binding region of human IL-10. In vitro studies confirm that the N-terminal region of BmHsp12.6 (N-BmHsp12.6) has IL-10 like activity and the region containing the alpha crystalline domain and C-terminus of BmHsp12.6 (BmHsp12.6αc) has no IL-10 like activity. However, BmHsp12.6αc contains B cell, T cell and CTL epitopes. Members of the sHSP families are excellent vaccine candidates. Evaluation of sera samples from putatively immune endemic normal (EN) subjects showed IgG1 and IgG3 antibodies against BmHsp12.6αc and these antibodies were involved in the ADCC mediated protection. Subsequent vaccination trials with BmHsp12.6αc in a mouse model using a heterologous prime boost approach showed that 83% protection can be achieved against B. malayi L3 challenge. Results presented in this study thus show that the N-BmHsp12.6 subunit of BmHsp12.6 has immunoregulatory function, whereas, the BmHsp12.6αc subunit of BmHsp12.6 has significant vaccine potential.Gajalakshmi DakshinamoorthyAbhilash Kumble SamykuttyGnanasekar MunirathinamGangadhar Bhaurao ShindeThomas NutmanMaryada Venkatarami ReddyRamaswamy KalyanasundaramPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34077 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gajalakshmi Dakshinamoorthy Abhilash Kumble Samykutty Gnanasekar Munirathinam Gangadhar Bhaurao Shinde Thomas Nutman Maryada Venkatarami Reddy Ramaswamy Kalyanasundaram Biochemical characterization and evaluation of a Brugia malayi small heat shock protein as a vaccine against lymphatic filariasis.
description	Filarial nematodes enjoy one of the longest life spans of any human pathogen due to effective immune evasion strategies developed by the parasite. Among the various immune evasion strategies exhibited by the parasite, Interleukin 10 (IL-10) productions and IL-10 mediated immune suppression has significant negative impact on the host immune system. Recently, we identified a small heat shock protein expressed by Brugia malayi (BmHsp12.6) that can bind to soluble human IL-10 receptor alpha (IL-10R) and activate IL-10 mediated effects in cell lines. In this study we show that the IL-10R binding region of BmHsp12.6 is localized to its N-terminal region. This region has significant sequence similarity to the receptor binding region of human IL-10. In vitro studies confirm that the N-terminal region of BmHsp12.6 (N-BmHsp12.6) has IL-10 like activity and the region containing the alpha crystalline domain and C-terminus of BmHsp12.6 (BmHsp12.6αc) has no IL-10 like activity. However, BmHsp12.6αc contains B cell, T cell and CTL epitopes. Members of the sHSP families are excellent vaccine candidates. Evaluation of sera samples from putatively immune endemic normal (EN) subjects showed IgG1 and IgG3 antibodies against BmHsp12.6αc and these antibodies were involved in the ADCC mediated protection. Subsequent vaccination trials with BmHsp12.6αc in a mouse model using a heterologous prime boost approach showed that 83% protection can be achieved against B. malayi L3 challenge. Results presented in this study thus show that the N-BmHsp12.6 subunit of BmHsp12.6 has immunoregulatory function, whereas, the BmHsp12.6αc subunit of BmHsp12.6 has significant vaccine potential.
format	article
author	Gajalakshmi Dakshinamoorthy Abhilash Kumble Samykutty Gnanasekar Munirathinam Gangadhar Bhaurao Shinde Thomas Nutman Maryada Venkatarami Reddy Ramaswamy Kalyanasundaram
author_facet	Gajalakshmi Dakshinamoorthy Abhilash Kumble Samykutty Gnanasekar Munirathinam Gangadhar Bhaurao Shinde Thomas Nutman Maryada Venkatarami Reddy Ramaswamy Kalyanasundaram
author_sort	Gajalakshmi Dakshinamoorthy
title	Biochemical characterization and evaluation of a Brugia malayi small heat shock protein as a vaccine against lymphatic filariasis.
title_short	Biochemical characterization and evaluation of a Brugia malayi small heat shock protein as a vaccine against lymphatic filariasis.
title_full	Biochemical characterization and evaluation of a Brugia malayi small heat shock protein as a vaccine against lymphatic filariasis.
title_fullStr	Biochemical characterization and evaluation of a Brugia malayi small heat shock protein as a vaccine against lymphatic filariasis.
title_full_unstemmed	Biochemical characterization and evaluation of a Brugia malayi small heat shock protein as a vaccine against lymphatic filariasis.
title_sort	biochemical characterization and evaluation of a brugia malayi small heat shock protein as a vaccine against lymphatic filariasis.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/fe05230b84d34207889cb379f50ef787
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Biochemical characterization and evaluation of a Brugia malayi small heat shock protein as a vaccine against lymphatic filariasis.

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