Ancylostoma secreted protein 2 (ASP-2)

Ancylostoma secreted protein 2 (ASP-2) is a major excretory-secretory protein produced by the infective third-stage larvae (L3) of hookworms, such as Necator americanus and Ancylostoma caninum [1, 5]. It belongs to the CAP (Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-related 1) superfamily and is characterized by a netrin-like fold, which is structurally similar to tissue inhibitors of metalloproteinases [3, 11]. ASP-2 is released by the larvae upon host entry and plays a critical role in the transition to parasitism, likely by modulating the host's immune response through the recruitment of neutrophils and potentially acting as a cytokine decoy [8, 16]. Due to its high expression and essential role in early infection, ASP-2 was developed as a lead recombinant vaccine candidate (Na-ASP-2) to prevent hookworm-associated anemia and morbidity [7, 13]. While clinical trials in unexposed individuals demonstrated that the vaccine was immunogenic and well-tolerated, trials in hookworm-endemic regions were halted due to the occurrence of generalized urticaria [1, 17]. This adverse reaction was linked to pre-existing IgE antibodies against ASP-2 from prior natural infections, presenting a significant challenge for the development of helminth vaccines in endemic populations [2, 17].

Other names

Ancylostoma-secreted protein 2Na-ASP-2Ac-ASP-2AceES-2Helminth antigen ASP-2Pathogenesis-related protein 1 family member

Induction of neutralizing antibodies (IgG) and cellular immune responses to prevent larval invasion, migration, and establishment within the host [12, 13, 16].