RESEARCH ARTICLE
Characterization of a Broadly Reactive AntiCD40 Agonistic Monoclonal Antibody for Potential Use as an Adjuvant Cameron Martin1, Suryakant D. Waghela1, Shehnaz Lokhandwala1, Andy Ambrus1, Jocelyn Bray1, Christina Vuong1, Vanitha Vinodkumar1, Paul J. Dominowski2, Sharath Rai2, Duncan Mwangi2, Dennis L. Foss2, Waithaka Mwangi1* 1 Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, United States of America, 2 Zoetis, Kalamazoo, Michigan, United States of America
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OPEN ACCESS Citation: Martin C, Waghela SD, Lokhandwala S, Ambrus A, Bray J, Vuong C, et al. (2017) Characterization of a Broadly Reactive Anti-CD40 Agonistic Monoclonal Antibody for Potential Use as an Adjuvant. PLoS ONE 12(1): e0170504. doi:10.1371/journal.pone.0170504 Editor: Gourapura J. Renukaradhya, The Ohio State University, UNITED STATES Received: September 15, 2016 Accepted: January 5, 2017 Published: January 20, 2017 Copyright: © 2017 Martin 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. Data Availability Statement: All relevant data are within the paper and its supporting Information files. Funding: The funder provided support to conduct this study. The following authors, DF, PD, SR, and DM, are employees of the funder. These authors helped by reviewing/revising the manuscript, data analysis, and validating result. The funder did not play a role in the decision to publish, study design, or data collection.
* [email protected]
Abstract Lack of safe and effective adjuvants is a major hindrance to the development of efficacious vaccines. Signaling via CD40 pathway leads to enhanced antigen processing and presentation, nitric oxide expression, pro-inflammatory cytokine expression by antigen presenting cells, and stimulation of B-cells to undergo somatic hypermutation, immunoglobulin class switching, and proliferation. Agonistic anti-CD40 antibodies have shown promising adjuvant qualities in human and mouse vaccine studies. An anti-CD40 monoclonal antibody (mAb), designated 2E4E4, was identified and shown to have strong agonistic effects on primary cells from multiple livestock species. The mAb recognize swine, bovine, caprine, and ovine CD40, and evoked 25-fold or greater proliferation of peripheral blood mononuclear cells (PBMCs) from these species relative to cells incubated with an isotype control (p
Characterization of a Broadly Reactive AntiCD40 Agonistic Monoclonal Antibody for Potential Use as an Adjuvant Cameron Martin1, Suryakant D. Waghela1, Shehnaz Lokhandwala1, Andy Ambrus1, Jocelyn Bray1, Christina Vuong1, Vanitha Vinodkumar1, Paul J. Dominowski2, Sharath Rai2, Duncan Mwangi2, Dennis L. Foss2, Waithaka Mwangi1* 1 Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, United States of America, 2 Zoetis, Kalamazoo, Michigan, United States of America
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OPEN ACCESS Citation: Martin C, Waghela SD, Lokhandwala S, Ambrus A, Bray J, Vuong C, et al. (2017) Characterization of a Broadly Reactive Anti-CD40 Agonistic Monoclonal Antibody for Potential Use as an Adjuvant. PLoS ONE 12(1): e0170504. doi:10.1371/journal.pone.0170504 Editor: Gourapura J. Renukaradhya, The Ohio State University, UNITED STATES Received: September 15, 2016 Accepted: January 5, 2017 Published: January 20, 2017 Copyright: © 2017 Martin 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. Data Availability Statement: All relevant data are within the paper and its supporting Information files. Funding: The funder provided support to conduct this study. The following authors, DF, PD, SR, and DM, are employees of the funder. These authors helped by reviewing/revising the manuscript, data analysis, and validating result. The funder did not play a role in the decision to publish, study design, or data collection.
* [email protected]
Abstract Lack of safe and effective adjuvants is a major hindrance to the development of efficacious vaccines. Signaling via CD40 pathway leads to enhanced antigen processing and presentation, nitric oxide expression, pro-inflammatory cytokine expression by antigen presenting cells, and stimulation of B-cells to undergo somatic hypermutation, immunoglobulin class switching, and proliferation. Agonistic anti-CD40 antibodies have shown promising adjuvant qualities in human and mouse vaccine studies. An anti-CD40 monoclonal antibody (mAb), designated 2E4E4, was identified and shown to have strong agonistic effects on primary cells from multiple livestock species. The mAb recognize swine, bovine, caprine, and ovine CD40, and evoked 25-fold or greater proliferation of peripheral blood mononuclear cells (PBMCs) from these species relative to cells incubated with an isotype control (p
