N. americanus ASP-2 (Na-ASP-2) was selected as the most promising vaccine candidate targeting the larval stage of hookworm infections. Dogs vaccinated with A. caninum irL3 produced a direct antibody response to the antigen ASP-2. Furthermore, high concentrations of IgG antibodies were observed after vaccination of dogs and hamsters with recombinant A. caninum or Ancylostoma ceylanicum ASP-2. There was an observed robust secondary immune response in these animals after infection with L3, producing low levels of adult hookworms, fecal counts and reduced blood loss. Anti-ASP-2 IgG collected from vaccinated animals prevented the movement of larval hookworms throughout tissue samples. Studies of regions where hookworm is endemic showed that anti-ASP-2 antibodies are correlated with reduced risk of hookworm infections. 

N. americanus ASP-2 (Na-ASP-2)

The function of ASPs are unknown, imaging of these proteins indicates roles in proteolysis and modification of the immune system. These proteins have been isolated from products of N. americanus. 

Tulane University

The incubation of hookworm L3 (indicates an infective third stage of exposure) with serum replicates the conditions of hookworm invasion of host tissues. Subsequently, there is a release of three products:
- Metalloprotease
- 2 proteins from the pathogenesis superfamily, Ancylostoma Secreted Protein (ASP)–1 and ASP-2

Larval Antigens

Stanley Plotkin, David J. Diemert, Jeffrey M. Bethony, Peter J. Hotez, Hookworm Vaccines, Clinical Infectious Diseases, Volume 46, Issue 2, 15 January 2008, Pages 282–288, https://doi.org/10.1086/524070

Hookworm Vaccines

ASPs

The three products of L3 have been developed as recombinant proteins in laboratory settings. Two extracellular, surface proteins (Ac-SAA–1 and Ac-16) have demonstrated a successful immune response and may produce an efficacious vaccine. Ac-16 is a larval surface protein that can reduce egg counts, reproduction rate and, as a result, blood loss in vaccinated dogs. 

Activation of L3 has produced 3 major products:

Adult hookworms, located in the host’s GI tract, will continuously ingest blood that is then ruptured in the worm’s digestive system. As a result, there is a release of hemoglobin that will be broken down by a protein cascade. These proteins have been identified and the vaccination of humans with these antigens may induce antibodies that can be ingested by the worm. These antibodies would disrupt these protein cascades and the worm’s digestive pathway, reducing the likelihood that the adult hookworm will survive. 

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