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Open AccessArticle

Safety Studies of Pneumococcal Endolysins Cpl-1 and Pal

1
Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla Street 12, 53-114 Wroclaw, Poland
2
Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA
3
Research and Development Center, Regional Specialized Hospital, 51-124 Wrocław, Poland
4
Perlan Technologies Sp. z o. o., 02-785 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Current address: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY 10065, USA.
Viruses 2018, 10(11), 638; https://doi.org/10.3390/v10110638
Received: 8 August 2018 / Revised: 9 November 2018 / Accepted: 13 November 2018 / Published: 15 November 2018
(This article belongs to the Special Issue Biotechnological Applications of Phage and Phage-Derived Proteins)
Bacteriophage-derived endolysins have gained increasing attention as potent antimicrobial agents and numerous publications document the in vivo efficacy of these enzymes in various rodent models. However, little has been documented about their safety and toxicity profiles. Here, we present preclinical safety and toxicity data for two pneumococcal endolysins, Pal and Cpl-1. Microarray, and gene profiling was performed on human macrophages and pharyngeal cells exposed to 0.5 µM of each endolysin for six hours and no change in gene expression was noted. Likewise, in mice injected with 15 mg/kg of each endolysin, no physical or behavioral changes were noted, pro-inflammatory cytokine levels remained constant, and there were no significant changes in the fecal microbiome. Neither endolysin caused complement activation via the classic pathway, the alternative pathway, or the mannose-binding lectin pathway. In cellular response assays, IgG levels in mice exposed to Pal or Cpl-1 gradually increased for the first 30 days post exposure, but IgE levels never rose above baseline, suggesting that hypersensitivity or allergic reaction is unlikely. Collectively, the safety and toxicity profiles of Pal and Cpl-1 support further preclinical studies. View Full-Text
Keywords: endolysin; Pal; Cpl-1; safety; toxicity; immune response; Streptococcus pneumoniae endolysin; Pal; Cpl-1; safety; toxicity; immune response; Streptococcus pneumoniae
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Harhala, M.; Nelson, D.C.; Miernikiewicz, P.; Heselpoth, R.D.; Brzezicka, B.; Majewska, J.; Linden, S.B.; Shang, X.; Szymczak, A.; Lecion, D.; Marek-Bukowiec, K.; Kłak, M.; Wojciechowicz, B.; Lahutta, K.; Konieczny, A.; Dąbrowska, K. Safety Studies of Pneumococcal Endolysins Cpl-1 and Pal. Viruses 2018, 10, 638.

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