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Open AccessArticle

Autotransporter-Mediated Display of Complement Receptor Ligands by Gram-Negative Bacteria Increases Antibody Responses and Limits Disease Severity

1
Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA
2
Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA
3
Department of Infectious Disease, Southern Research Institute, Birmingham, AL 35211, USA
*
Author to whom correspondence should be addressed.
Current addresses: A.S.―Department of Neurobiology, University of Alabama, Birmingham, AL 35233, USA; T.J.S.―Chief Scientific Officer, Global Lyme Alliance, Stamford, CT 06902, USA.
Pathogens 2020, 9(5), 375; https://doi.org/10.3390/pathogens9050375
Received: 24 April 2020 / Revised: 6 May 2020 / Accepted: 11 May 2020 / Published: 14 May 2020
The targeting of immunogens/vaccines to specific immune cells is a promising approach for amplifying immune responses in the absence of exogenous adjuvants. However, the targeting approaches reported thus far require novel, labor-intensive reagents for each vaccine and have primarily been shown as proof-of-concept with isolated proteins and/or inactivated bacteria. We have engineered a plasmid-based, complement receptor-targeting platform that is readily applicable to live forms of multiple gram-negative bacteria, including, but not limited to, Escherichia coli, Klebsiella pneumoniae, and Francisella tularensis. Using F. tularensis as a model, we find that targeted bacteria show increased binding and uptake by macrophages, which coincides with increased p38 and p65 phosphorylation. Mice vaccinated with targeted bacteria produce higher titers of specific antibody that recognizes a greater diversity of bacterial antigens. Following challenge with homologous or heterologous isolates, these mice exhibited less weight loss and/or accelerated weight recovery as compared to counterparts vaccinated with non-targeted immunogens. Collectively, these findings provide proof-of-concept for plasmid-based, complement receptor-targeting of live gram-negative bacteria. View Full-Text
Keywords: plug & play; vaccine-targeting; gram-negative; complement; autotransporter; tularemia plug & play; vaccine-targeting; gram-negative; complement; autotransporter; tularemia
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Holland-Tummillo, K.M.; Shoudy, L.E.; Steiner, D.; Kumar, S.; Rosa, S.J.; Namjoshi, P.; Singh, A.; Sellati, T.J.; Gosselin, E.J.; Hazlett, K.R. Autotransporter-Mediated Display of Complement Receptor Ligands by Gram-Negative Bacteria Increases Antibody Responses and Limits Disease Severity. Pathogens 2020, 9, 375.

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