Hookworm vaccine is avaccine againsthookworm.[1] No effective vaccine for the disease in humans has yet been developed. Hookworms, parasiticnematodes transmitted in soil, infect approximately 700 million humans, particularly intropical regions of the world where endemic hookworms includeAncylostoma duodenale andNecator americanus. Hookworms feed onblood and those infected with hookworms may develop chronicanaemia andmalnutrition.[1][2]Helminth infection can be effectively treated withbenzimidazole drugs (such asmebendazole oralbendazole), and efforts led by theWorld 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 aboutdrug 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]
Hookworm infection is considered aneglected disease as it disproportionately affects poorer localities and has received little attention frompharmaceutical companies.[5]
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 interrupt or modulate—the hostimmune system.[1] Successful hookworm vaccines have been developed for several animal species.[1] On the basis of prior work, human vaccine development has targetedantigens from both the larval and adult stages of the hookworm life cycle; a combined vaccine for humans that would provide more complete protection.[1] Current targets of larval proteins attenuate larval migration through host tissue; targets of adult proteins have been demonstrated to blockenzymes vital to hookworm feeding.[citation needed]
The "ASP" (ancylostoma secreted protein) proteins arecysteine-rich secretory proteins. They 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 ofHainan Province,China, andMinas Gerais,Brazil.[6] The function ofNa-ASP-2 (Q7Z1H1) is not currently known (though it may function as achemotaxin mimic[1]), but it is known to be released during parasite entry into the host. It may have some function in the transition from the larval environment stage of the hookworm life-cycle to an adult parasitic existence and tissue migration.[2][7][8][9][10]
The "APR" proteins areaspartic proteases.Ac-APR-1 andNa-APR-1[11] specifically participate in the hookworm's digestion ofhemoglobin from its blood meal[4] and are present in the adult stage of the hookworm life cycle.[1][4] Animals immunized againstAc-APR-1 exhibited a reduction in worm burden, a reduction in hemoglobin loss, and a dramatic reduction in wormfecundity.[2]
The "GST" proteins areglutathione S-transferases.Na-GST-1 (D3U1A5) plays a role in the worm's digestion of hemoglobin; specifically, it serves to protect the worm fromheme molecules released by digestion.[12]
Examples of antigenic targets of hookworm vaccines currently inclinical trials includeNa-ASP-2,Ac-APR-1,Na-APR-1, andNa-GST-1.[12]
In a clinical trial a vaccine containing recombinant Na-ASP-2 withAluminium hydroxide (Alhydrogel) as anadjuvant was found to increaseTh2 helper cells andIgE. Both the Th2 helper cells and IgE antibody are important players in recognition and immunoregulation against parasites. The vaccine containing recombinant Na-ASP-2 resulted in significantly decreased risk of a hookworm infection.[7]
In 2014,Na-GST-1 with Alhydrogel adjuvant completed a successful phase 1 clinical trial in Brazil. In 2017, it completed a successful phase 1 trial in the US.[12]
Research funding to develop hookworm vaccines has come from the Human Hookworm Vaccine Initiative,[13] a program of theSabin Vaccine Institute and collaborations withGeorge Washington University, theOswaldo Cruz Foundation, theChinese Institute of Parasitic Diseases, theQueensland Institute of Medical Research, and theLondon School of Hygiene and Tropical Medicine.[2][14][15] Funding for hookworm vaccine research efforts also includes funds from theBill & Melinda Gates Foundation totaling in excess of $53 million,[5] and additional support from theRockefeller Foundation,Doctors Without Borders,National Institute of Allergy and Infectious Diseases, and theMarch of Dimes Birth Defects Foundation.[5][15]
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.[16]