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Immunogenicity of Endolysin PlyC.
Marek Adam Harhala1,2, Katarzyna Gembara1,2, Daniel C Nelson3
1Laboratory of Phage Molecular Biology, Department of Phage Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland.
Antibiotics (Basel, Switzerland)
|July 27, 2022
Summary
Bacteriophage endolysins like PlyC show promise as antibiotic alternatives. While immunogenic, PlyC does not induce hypersensitivity, with no PlyC-specific IgE detected in mice or humans.
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Endolysins are bacteriolytic enzymes from bacteriophages, offering an alternative to conventional antibiotics due to their resistance to antimicrobial resistance mechanisms.
- Non-human proteins can elicit specific immune responses, including IgG and IgE-mediated allergic reactions.
- Evaluating the immunogenicity and hypersensitivity potential of endolysins is crucial for their therapeutic development.
Purpose of the Study:
- To assess the general immunogenicity of the antibacterial enzyme PlyC in a human population and a mouse model.
- To identify molecular epitopes of PlyC responsible for immune interactions.
- To evaluate the potential for hypersensitivity and detect PlyC-specific IgE.
Main Methods:
- Immunization of a mouse model with PlyC.
- Analysis of PlyC-specific IgG responses and epitope mapping.
- Screening of human serum samples for IgG reactivity to PlyC subunits.
- Assessment of hypersensitivity and IgE responses in mice and humans.
Main Results:
- PlyC induced significant IgG production in mice, with IgG interacting with four immunogenic regions on the PlyCA subunit.
- Approximately 10% of the human population exhibited IgG reactivity to the PlyCB subunit, likely due to cross-reactions in naive serum.
- No PlyC-specific IgE was detected in either the mouse model or the human population, indicating a lack of hypersensitivity.
Conclusions:
- PlyC is immunogenic, inducing a robust IgG response without causing hypersensitivity.
- The identified immunogenic regions on PlyC provide targets for further immunological studies.
- The absence of PlyC-specific IgE suggests a favorable safety profile for potential therapeutic applications of endolysins.

