Target intelligence / Profile preview

Agglutinin-like sequence protein 3 (Als3) (Als3)

Target
Als3
Molecular classification
Adhesin, Invasin, GPI-anchored protein, Cell surface protein
01

Overview

Agglutinin-like sequence protein 3 (Als3) is a major cell-surface glycoprotein and essential virulence factor produced by the fungal pathogen Candida albicans during its hyphal growth phase [2, 4]. It belongs to the Agglutinin-Like Sequence (ALS) family and functions as a dual adhesin and invasin, facilitating fungal attachment to host epithelial and endothelial cells and inducing endocytosis through molecular mimicry of host cadherins [3, 5]. Als3 is also critical for the development of robust biofilms on medical devices and for the acquisition of iron from host ferritin, which is vital for fungal survival within the host environment [1, 2]. Due to its high expression in vivo and central role in pathogenesis, Als3 has been developed as a primary target for immunotherapeutic intervention [8, 11]. The most advanced candidate, the NDV-3A vaccine, has demonstrated the ability to induce protective antibody and T-cell responses in clinical trials, effectively reducing the recurrence of vulvovaginal candidiasis and showing potential for preventing invasive systemic infections [11, 13].

Other names
Agglutinin-like protein 3Als3pALS3ALS10ALS8Agglutinin-like sequence 3
02

Mechanism of action

Active immunization utilizing recombinant Als3 protein to induce high titers of neutralizing antibodies and Th1/Th17 cell-mediated immune responses that block fungal adhesion to host cells and prevent tissue invasion by inhibiting Als3-mediated binding to host cadherins.

03

Biological functions

Cell adhesionHost cell invasionBiofilm formationIron acquisitionFungal morphogenesisYeast-to-hyphae transition
04

Disease associations

CandidiasisVulvovaginal candidiasisInvasive candidiasisRecurrent vulvovaginal candidiasisBiofilm-associated infection
05

Safety considerations

Molecular mimicry with human cadherinsTherapeutic challenge in severely immunocompromised patients who cannot generate a robust immune response to vaccinationPotential for vaccine escape through upregulation of other ALS family members
06

Interacting drugs

NDV-3A

1 more in the full profile.

07

Biomarkers

Anti-Als3 IgG antibody titerAnti-Als3 IgG2 antibody titerALS3 mRNA expression levels

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