Vaccinomics for the Major Blood Feeding Helminths of Humans

Abstract

Approximately one billion people are infected with hookworms and/or blood flukes (schistosomes) in developing countries. These two parasites are responsible for more disability adjusted life years lost than most other neglected tropical diseases (NTDs), and together, are second only to malaria. Although anthelmintic drugs are effective and widely available, they do not protect against reinfection, resistant parasites are likely to emerge, and mass drug administration programs are unsustainable. Therefore, there is a pressing need for the development of vaccines against these parasites. In recent years, there have been major advances in our understanding of hookworms and schistosomes at the molecular level through the use of ''omics'' technologies. The secretomes of these parasites have been characterized using transcriptomics, genomics, proteomics, and newly developed gene manipulation and silencing techniques, and the proteins of interest are now the target of novel antigen discovery approaches, notably immunomics. This research has resulted in the discovery, development, and early stage clinical trials of subunit vaccines against hookworms and schistosomes.

Structure–function analysis of apical membrane‐associated molecules of the tegument of schistosome parasites of humans: prospects for identification of novel targets for parasite control

“…The alternative, a subunit vaccine, has thus been promoted as an important alternative strategy for the control and elimination of schistosomiasis (Bergquist et al, 2008;McManus and Loukas, 2008;Loukas et al, 2011;Kupferschmidt, 2013).…”

“…Of the vaccines trialled, a number have been promoted for human trials, including the Bilvax vaccine based on a 28 kDa S. haematobium glutathione-S-transferase, which has entered phase 3 clinical trials, and a S. mansoni tetraspanin (Sm-TSP-2) (Tran et al, 2006), which has entered phase 1 trials (Loukas et al, 2011;Kupferschmidt, 2013). Other vaccines presented at a recent vaccine discovery workshop sponsored by the Bill and Melinda Gates Foundation in the United States (Kupferschmidt, 2013) identified additional vaccines still in experimental development, including Sm14, a fatty acid binding protein, a calpain (Smp80) from S. mansoni, and Sj23, a TSP, a triose-phosphate isomerase, an insulin receptor, and paramyosin from S. japonicum (Zhu et al, 2004;Siddiqui et al, 2005;Tendler and Simpson, 2008;You et al, 2012).…”

Cysteine proteases of human hookwormNecator Americanus as virulencefactors and implications for drug design with anti-heparin and heparin analogs: A bioinformatics study

“…[1] [2] Necator Americanus (NA) species of hookworm constitutes the majority of these infections (~85%) [3] The clinical manifestation of the disease includes anemia, malnutrition in pregnant women, and cognitive and/or physical development impairment in children [4] . These helminth blood feeders on reaching maturity can feed up to 9ml of blood per day in an infected individual by attaching themselves to the intestinal mucosa of the host, through cutting plates as in NA [5] .…”

Probing the equatorial groove of the hookworm protein and vaccine candidate antigen, Na-ASP-2

“…Hookworms alone infect approximately 700 million people, mostly in impoverished communities in tropical and subtropical areas, causing a disease burden of 1.5-22.1 million disability-adjusted life years (DALYs) (Hotez et al, 2010). Necator americanus is the predominant hookworm globally, causing the disease necatoriasis, characterized clinically by anaemia, malnutrition in pregnant women and an impairment of cognitive and/or physical development (particularly in children) (Loukas et al, 2011). The control of hookworm disease rests on currently available anthelmintic drugs such as albendazole, mebendazole and/or pyrantel, which are used to reduce the burden of disease in a range of countries (Diemert et al, 2008).…”