Monoclonal Antibody-Based Therapeutics for Melioidosis and Glanders
- 1 Henry M. Jackson Foundation, United States
- 2 Walter Reed National Military Medical Center, United States
- 3 Walter Reed Army Institute of Research, United States
- 4 Center for Biologics Evaluation and Research, United States
Abstract
Problem statement: Burkholderia Pseudomallei (BP) and B. Mallei (BM) were two closely related pathogenic gram-negative bacteria. They were the causative agents of melioidosis and glanders, respectively and are recognized by CDC as category B select agents. Significant efforts had been devoted to developing the diagnostic and therapeutic measures against these two pathogens. Monoclonal antibody-based therapeutic was a promising targeted therapy to fight against melioidosis and glanders. Valuable findings have been reported by different groups in their attempt to identify vaccine targets against these two pathogens. Approach: Our group has generated neutralizing Monoclonal Antibodies (MAbs) against BP and BM and characterized them by both in vitro and in vivo experiments. We present an overview of the MAb-based therapeutic approaches against BP and BM and demonstrate some of our efforts for developing chimeric and fully human MAbs using antibody engineering. Results: Throughout conventional mouse hybridoma technique and antibody engineering (chimerization and in vitro antibody library techniques), we generated 10 chimeric MAbs (3 stable MAbs and 7 transient MAbs) and one fully human MAb against BP and BM. In addition, we present the reactive antigen profiles of these MAbs. Our approaches had potentials to accelerate the development of therapeutics for melioidosis and glanders in humans. Conclusion: Our experience and findings presented here will be valuable for choosing the best antigenic targets and ultimately for the production of effective vaccines for these two pathogens.
DOI: https://doi.org/10.3844/ajisp.2011.39.53
Copyright: © 2011 Hyung-Yong Kim, Alexander Stojadinovic, Peter J. Weina, Ho San Kim, Shyh-Ching Lo and Mina J. Izadjoo. 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.
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Keywords
- Melioidosis
- glanders
- Burkholderia pseudomallei
- B. mallei
- monoclonal antibody engineering