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Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
Synthetic conjugate peptide Fba-Met6 (MP12) induces complement-mediated resistance against disseminated Candida
Abby L Adams1, Karen Eberle1, Jonothan Rosario Colón1
1Louisiana State University Health Sciences Center, Department of Microbiology, Immunology, and Parasitology, 1901 Perdido St., New Orleans, LA 70112, USA.
Abstract:
The fungal genus Candida includes common commensals of the human mucosal membranes, and the most prevalently isolated species, C. albicans, poses a threat of candidemia and disseminated infection associated with an unacceptably high mortality rate and an immense $4 billion burden (US) yearly. Nevertheless, the demand for a vaccine remains wholly unfulfilled and increasingly pressing. We developed a double-peptide construct that is feasible for use in humans with the intention of preventing morbid infection by targeting epitopes derived from fructose bisphosphate aldolase (Fba) and methionine synthase (Met6) which are expressed on the C. albicans cell surface. To test the applicability of the design, we vaccinated mice via the intramuscular (IM) route with the conjugate denoted Fba-Met6 MP12 and showed that the vaccine enhanced survival against a lethal challenge. Because overall endpoint IgG1 and IgG2a antibody titers were robust and these mouse subclasses are associated with protective functionality, we investigated the potential of Fba and Met6 specific antibodies to facilitate the well-defined anti-Candida response by complement, which opsonizes fungi for degradation by primary effectors. Notably, reductions in the fungal burdens and enhanced survival were both abrogated in MP12-vaccinated mice that were pre-challenge dosed with cobra venom factor (CVF), a complement depleting factor. Altogether, we demonstrated that complement is relevant to MP12-based protection against disseminated C. albicans, delineating that a novel, multivalent targeted vaccine against proteins on the surface of C. albicans can enhance the natural response to infection.
Insights
A new vaccine targeting Candida albicans surface proteins, Fructose bisphosphate aldolase (Fba) and Methionine synthase (Met6), significantly improved survival in mice. This novel approach enhances the natural immune response against invasive fungal infections.
Area of Science:
- Immunology
- Mycology
- Vaccinology
Background:
- Candida albicans is a common human commensal causing life-threatening candidemia and disseminated infections.
- Invasive candidiasis presents a significant global health burden with high mortality rates and unmet vaccine needs.
Purpose of the Study:
- To develop and evaluate a novel, human-feasible vaccine targeting surface proteins of Candida albicans.
- To assess the efficacy of a double-peptide construct (Fba-Met6) in preventing invasive C. albicans infection.
Main Methods:
- Development of a conjugate vaccine (Fba-Met6 MP12) targeting epitopes from Fructose bisphosphate aldolase (Fba) and Methionine synthase (Met6).
- Intramuscular vaccination of mice with Fba-Met6 MP12, followed by lethal C. albicans challenge.
- Assessment of survival rates, antibody titers (IgG1, IgG2a), and the role of complement in vaccine-mediated protection using cobra venom factor (CVF).
Main Results:
- Vaccination with Fba-Met6 MP12 significantly enhanced survival against a lethal C. albicans challenge in mice.
- Robust IgG1 and IgG2a antibody titers were observed in vaccinated mice, indicating a strong adaptive immune response.
- Complement depletion abrogated the protective effects of the Fba-Met6 MP12 vaccine, highlighting its crucial role in anti-Candida immunity.
Conclusions:
- The novel Fba-Met6 MP12 vaccine demonstrates potential for preventing invasive C. albicans infections by engaging the complement system.
- This study validates a multivalent vaccine strategy targeting surface proteins to enhance the natural immune response against Candida.
- The findings support the development of a new vaccine to address the pressing need for preventing C. albicans-associated morbidity and mortality.
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