Agglutinin-like protein 3 (Als3p)

Agglutinin-like protein 3 (Als3p) is a hyphal-specific cell wall glycoprotein in Candida albicans that belongs to the agglutinin-like sequence (ALS) family. It serves as a multifunctional virulence factor, acting as both an adhesin that mediates attachment to host cells and extracellular matrix proteins, and an invasin that triggers host cell endocytosis by mimicking mammalian cadherins such as E-cadherin and N-cadherin. Als3p is also critical for the formation of robust biofilms on medical devices and facilitates fungal iron acquisition by binding to host ferritin. Because of its essential role in pathogenesis and high expression during infection, the N-terminal domain of Als3p has been utilized as the primary antigen in the NDV-3 and NDV-3A vaccines. These immunotherapies aim to elicit protective antibody and T-cell responses to prevent various forms of candidiasis, including recurrent vulvovaginal and disseminated infections. Clinical trials have demonstrated the safety and immunogenicity of targeting this domain, showing significant protection in specific patient populations. Beyond vaccines, Als3p is a target for several monoclonal antibodies that block its adhesive and invasive functions. The protein's unique expression on hyphae makes it a specific marker for the invasive phase of the fungus.

Other names

Agglutinin-like sequence 3 proteinAls3rAls3p-NCandida albicans Als3pAgglutinin-like protein 3 N-terminal domain

Vaccination with the recombinant N-terminal domain of Als3p (rAls3p-N) induces protective Th1 and Th17 cellular immune responses and high titers of neutralizing antibodies, particularly the IgG2 subclass. These antibodies block fungal adhesion to host tissues, inhibit invasion by preventing binding to host cadherins, and enhance opsonophagocytic killing by neutrophils and macrophages.