Recombinant Na-ASP-2 has been expressed in yeast colonies, Pichia pastoris, and artificially modified to increase expression and yield. Antibodies collected from serum samples vaccinated laboratory animals recognize the larval antigen and inhibit larval migration. Furthermore, radiographic crystallographic analysis shows that the recombinant protein produces the same pathogenesis-related-1 domain as the natural ASP-2 antigen. Therefore, the data suggests that recombinant -Na-ASP-2 has structural conformations similar to those of native ASP-2. 

Development of Na-ASP-2

A phase 1 study, conducted in the United States, of adults that had not been exposed to hookworm was performed from 2005-2006. 
Sample: 
- 36 healthy adults

Methods:
- randomized, double-blind, placebo-controlled study 
- 3 different concentrations of Na-ASP-2 were used
- patients were observed after 6 months of administering the vaccine

Safety Profile:
The vaccine was efficacious and safe. Adverse events included injection site reactions, swelling, erythema and pruritus. 


Phase 1 Study

Pre-clinical testing and manufacture of Na-ASP-2 from N. americanus were finalized in 2004. Clinical testing was expected to take place in 2005 following approval from the FDA. This vaccine will be developed in the nonprofit sector and distribution will be targeted to populations of susceptible individuals in moderately and/or heavily impacted regions. 

Tulane University

The Human Hookworm Vaccine Initiative (HHVI) is in the process of developing a functional and safe vaccine. HHVI is a non-profit collaboration at the George Washington University, London School of Hygiene and Tropical Medicine and the Oswaldo Cruz Foundation (vaccine development has been sponsored by the Sabin Vaccine Institute). Hookworm vaccine development involves research, process development, vaccine manufacturing and control and pre-clinical/clinical testing. 

Na-ASP-2 Hookworm Vaccine

Hookworm: “The Great Infection of Mankind”
Hotez PJ, Bethony J, Bottazzi ME, Brooker S, Buss P (2005) Hookworm: “The Great Infection of Mankind”. PLOS Medicine 2(3): e67. https://doi.org/10.1371/journal.pmed.0020067

Hookworm: "The Great Infection of Mankind"

The hookworm larval antigen (ASP-3) was identified as a protective antigen linked to recent larval vaccines. Additionally, there is a positive correlation between human anti-ASP-2 antibodies and the reduction of heavy-intensity hookworm infection in populations endemic to hookworm. Data has confirmed that recombinant ASP-2 can partially protect animals against larval hookworm infections. 

Vaccine Construction

Vaccine Development Process

Immunization would affect the transmission of hookworm larvae and not adult parasites living within the gastrointestinal tract of infected individuals. Therefore, the first dose would need to be administered after deworming. Vaccination administration would rely on established infrastructure, such as school wide deworming programs. Given that hookworm infections impact impoverished populations, there is a small commercial market available. Investment for manufacturing and industrial scale-up is still necessary to provide the vaccine to marginalized communities. 

Distribution of the Vaccine

Hookworm vaccines will primarily affect the larval stage of the parasitic worm by inducing the production of IgG antibodies. These antibodies will prevent larval development, reducing the population of larvae that develop into adult worms. This will lower mortality rates by preventing the adult hookworms from entering the host’s gastrointestinal tract and producing intestinal blood loss. 

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