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Agglutinin-like sequence 3 (Als3) is a critical cell surface protein and virulence factor of the opportunistic fungal pathogen Candida albicans. It belongs to the Als family of adhesins and is uniquely expressed during the hyphal phase of the fungus. Als3 functions as both an adhesin, mediating attachment to various host substrates, and an invasin, inducing its own endocytosis by host epithelial and endothelial cells through molecular mimicry of host cadherins such as E-cadherin and N-cadherin. Beyond its role in tissue invasion, Als3 is essential for biofilm formation on medical devices and facilitates iron acquisition from host ferritin. Due to its surface accessibility and central role in pathogenesis, Als3 is a primary target for immunotherapeutic development, including the NDV-3A vaccine, which has shown promise in clinical trials for preventing recurrent vulvovaginal candidiasis and systemic fungal infections.
Vaccination with the recombinant N-terminal domain of Als3 (rAls3p-N) induces high titers of anti-Als3 antibodies and a robust Th1/Th17 cellular immune response. These antibodies block the fungal protein's ability to adhere to and invade host tissues. Monoclonal antibodies like MAbC7 directly bind to the N-terminal domain of Als3, preventing its interaction with host receptors like E-cadherin and N-cadherin, thereby inhibiting fungal endocytosis and tissue damage.
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