A Redox-Responsive β-Glucan-Based Vaccine Recruiting Endogenous Antibodies to Potentiate Antifungal Immunity

Area of Science:

• Immunology
• Vaccinology
• Microbiology

Background:

• Invasive fungal infections, especially from Candida albicans, are a significant health concern, particularly for immunocompromised individuals.
• Surface-exposed β-glucans on Candida albicans are potential vaccine targets, but conventional glycoconjugate vaccines have limited immunogenicity.

Purpose of the Study:

• To develop an innovative vaccine strategy that enhances antigen delivery to antigen-presenting cells (APCs) by recruiting endogenous antibodies.
• To improve the immunogenicity and efficacy of antifungal vaccines against Candida albicans.

Main Methods:

• A novel glycoconjugate vaccine (β-glucans-BSA-L2-Rha) was synthesized by conjugating β-glucans to bovine serum albumin (BSA) and coupling rhamnose (Rha) haptens via a redox-responsive disulfide linker.
• The vaccine design incorporated a redox-responsive linker to facilitate endosomal escape and antigen processing.
• Immunological evaluations were performed to assess the vaccine's efficacy and immune response generation.

Main Results:

• The presence of endogenous anti-rhamnose (Rha) antibodies significantly enhanced immune responses against the vaccine construct.
• The redox-responsive glycoconjugate elicited the strongest immune reactivity.
• Antisera generated by the vaccine effectively recognized the hyphal form of heat-killed Candida albicans (HKCA).

Conclusions:

• The developed vaccine strategy, utilizing endogenous antibodies and a redox-responsive linker, broadly enhances immune responses against Candida albicans.
• This approach offers a promising platform for developing more effective antifungal vaccines.
• The strategy of recruiting endogenous antibodies represents a significant advancement in vaccine design for infectious diseases.