Hookworm vaccine

Hookworm vaccine

Hookworm vaccine is a vaccine against hookworm.[1] No effective vaccine for the disease has yet been developed. Hookworms, parasitic nematodes transmitted in soil, infect approximately 700 million humans, particularly in tropical regions of the world where endemic hookworms include Ancylostoma duodenale and Necator americanus. Hookworms feed on blood and those infected with hookworms may suffer from chronic anaemia and malnutrition.[1][2] Helminth infection can be effectively treated with benzimidazole drugs (such as mebendazole or albendazole), and efforts led by the World Health Organization have focused on one to three yearly de-worming doses in schools because hookworm infections with the heaviest intensities are most common in school-age children.[3] However, these drugs only eliminate existing adult parasites and re-infection can occur soon after treatment, school-based de-worming efforts do not treat adults or pre-school children, and concerns exist about drug resistance developing in hookworms against the commonly used treatments, thus a vaccine against hookworm disease is sought to provide more permanent resistance to infection.[3][4]

Mechanism of action

Hookworm infections in humans can last for several years, and re-infection can occur very shortly after treatment, suggesting that hookworms effectively evade—and may interfere or modulate—the host immune system.[1] While this would suggest that vaccine development may be difficult, successful hookworm vaccines have been developed for several animal species.[1] On the basis of prior work, human vaccine development has targeted antigens from both the larval and adult stages of the hookworm life cycle; a combined vaccine for humans that would provide more complete protection against hookworm infection.[1] Current targets of larval proteins have been demonstrated to attenuate larval migration through host tissue; targets of adult proteins have been demonstrated to block enzymes vital to hookworm feeding.

Examples of antigenic targets of hookworm vaccines currently being investigated in clinical trials include Na-ASP-2 from N. americanus and Ac-APR-1 from Ancylostoma caninum.

The function of Na-ASP-2 is not currently known (though it may function as a chemotaxin mimic[1]), but it is a cysteine-rich secretory protein that is released during parasite entry into the host and may have some function in the transition from the larval environment stage of the hookworm life-cycle to an adult parasitic existence.[2][5][6][7] The class of proteins that includes Na-ASP-2, ASPs, are promising vaccine candidates based on previous vaccine studies in sheep, guinea pigs, cattle, and mice, which have demonstrated inhibition of hookworm larval migration. Furthermore, epidemiologic studies determined that high titers of circulating antibodies against ASPs are associated with lower hookworm burdens in residents of Hainan Province, China, and Minas Gerais, Brazil.[8]

Ac-APR-1 is an aspartic protease, specifically a hemoglobinase, that participates in the hookworm's digestion of hemoglobin from its blood meal[4] and is present in the adult stage of the hookworm life cycle.[1][4] Animals immunized against Ac-APR-1 exhibited a reduction in worm burden, a reduction in hemoglobin loss, and a dramatic reduction in worm fecundity.[2]

Research support

Hookworm infection has been considered a "neglected disease" that disproportionately affects poorer localities and has received little attention from pharmaceutical companies.[9] Support for current research efforts to develop hookworm vaccines has come from the Human Hookworm Vaccine Initiative,[10] a program of the Sabin Vaccine Institute and collaborations with George Washington University, the Oswaldo Cruz Foundation, the Chinese Institute of Parasitic Diseases, the Queensland Institute of Medical Research, and the London School of Hygiene and Tropical Medicine.[2][11][12] Funding for hookworm vaccine research efforts includes substantial money from the Bill & Melinda Gates Foundation,[13][14] totaling in excess of $53 million,[9] and additional support from the Rockefeller Foundation, Doctors Without Borders, National Institute of Allergy and Infectious Diseases, and the March of Dimes Birth Defects Foundation.[9][12]

The government of Brazil, where hookworm is still endemic in some poorer areas, has promised to manufacture a vaccine if one can be proven effective.[15]

References

External links

  • ClinicalTrials.gov
  • ClinicalTrials.gov