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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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Title: Biochemical Characterization and Evaluation of a Brugia malayi Small Heat Shock Protein as a Vaccine Against Lymphatic Filariasis
Author(s): Dakshinamoorthy, Gajalakshmi; Samykutty, Abhilash Kumble; Munirathinam, Gnanasekar; Shinde, Gangadhar Bhaurao; Nutman, Thomas; Thomas, Maryada Venkatarami; Kalyanasundaram, Ramaswamy
Abstract: 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.
Issue Date: 2012-04
Publisher: Public Library of Science
Citation Info: Dakshinamoorthy, G., Samykutty, A. K., Munirathinam, G., Shinde, G. B., Nutman, T., Reddy, M. V., & Kalyanasundaram, R. 2012. Biochemical Characterization and Evaluation of a Brugia malayi Small Heat Shock Protein as a Vaccine against Lymphatic Filariasis. PLoS One, 7(3): e34077. doi:10.1371/journal.pone.0034077
Type: Article
Description: © 2012 Dakshinamoorthy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. doi:10.1371/journal.pone.0034077
URI: http://hdl.handle.net/10027/8450
ISSN: 1932-6203
Sponsor: This study was funded by an NIH RO1 grant (AI064745). Additional funding was received from the Department of Biotechnology, Ministry of Science and Technology, New Delhi (BT/INF/22/1/2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Date Available in INDIGO: 2012-08-14
 

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