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A Contemporary Warming/Restraining Device for Efficient Tail Vein Injections in a Murine Fungal Sepsis Model
Published on: November 6, 2020
Vaccine and monoclonal antibody that enhance mouse resistance to candidiasis
1Department of Pediatrics, Louisiana State University Health Sciences Center and Research Institute for Children, Children’s Hospital, New Orleans, Louisiana 70118, USA. hxin@chnola-research.org
Abstract:
Previously we showed that antibodies specific for the glycan β-1,2-mannotriose [β-(Man)(3)] on the cell surface of Candida albicans protect mice against disseminated candidiasis (H. Xin, S. Dziadek, D. R. Bundle, and J. E. Cutler, Proc. Natl. Acad. Sci. U. S. A. 105:13526-13531, 2008). Furthermore, six 14-mer peptides that are within the N-terminal portion of C. albicans wall proteins were conjugated to the glycan in an attempt to create immunogenic glycopeptide conjugates. By a dendritic cell (DC)-based immunization approach, all were immunogenic and three of the six conjugates induced a high degree of protection in mice. Interestingly, whereas all six peptides induced antibody responses when used alone to pulse DCs for subsequent immunizations, three peptides induced protection, and one in particular, peptide Fba (derived from fructose-bisphosphate aldolase), induced robust protective responses and is the focus of the current work. Fba peptide is not restricted by the major histocompatibility complex class II (MHC-II), as it induced anti-Fba antibodies in mice of different H-2 haplotypes and in rabbits. Furthermore, the peptide induced protection against disease caused by different C. albicans strains. Partial protection was achieved when alum was used in place of DCs for Fba immunizations. The passive transfer of immune sera from Fba-vaccinated mice, but not immune serum preabsorbed with fungal cells, conferred protection in naïve mice. This result, along with our finding that a monoclonal antibody specific for the peptide, E2-9 (IgM), protected mice against candidiasis, provide strong evidence that antibodies contribute to protection. Our work demonstrates the utility of cell wall peptides alone or as glycopeptides in vaccines designed for the induction of immunity against candidiasis and monoclonal antibodies as a rapid immunoprotective approach against the disease.
Insights
Antibodies targeting Candida albicans cell wall peptides, like Fba, offer protection against candidiasis. This research highlights the potential of peptide-based vaccines and monoclonal antibodies for treating fungal infections.
Area of Science:
- Immunology
- Microbiology
- Vaccine Development
Background:
- Candida albicans is a significant cause of opportunistic fungal infections.
- Previous studies demonstrated that antibodies against the glycan β-1,2-mannotriose protect against candidiasis.
- Developing effective vaccines and immunotherapies against candidiasis remains a critical challenge.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of Candida albicans cell wall peptides, particularly Fba peptide, as vaccine candidates.
- To investigate the role of antibodies in protection against candidiasis induced by peptide-based immunizations.
- To explore the potential of monoclonal antibodies as a rapid immunoprotective strategy.
Main Methods:
- Conjugation of 14-mer peptides from C. albicans wall proteins to a protective glycan.
- Immunization of mice using dendritic cells (DCs) or alum with glycopeptide conjugates or peptides alone.
- Assessment of antibody responses and protection against disseminated candidiasis.
- Testing peptide efficacy across different C. albicans strains and MHC-II haplotypes.
- Passive transfer of immune sera and administration of a specific monoclonal antibody (E2-9).
Main Results:
- Three out of six glycopeptide conjugates induced significant protection against candidiasis.
- The Fba peptide, derived from fructose-bisphosphate aldolase, induced robust protective responses independently of MHC-II.
- Fba peptide immunization conferred protection against various C. albicans strains.
- Passive transfer of anti-Fba antibodies and administration of anti-Fba monoclonal antibody (E2-9) provided protection.
- Partial protection was achieved using alum as an adjuvant instead of DCs.
Conclusions:
- Cell wall peptides, such as Fba, are promising vaccine components for inducing immunity against candidiasis.
- Antibodies play a crucial role in the protective immunity elicited by these peptides.
- Monoclonal antibodies targeting specific fungal antigens offer a rapid immunoprotective approach against candidiasis.
