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[Display omitted] • Hookworms, whipworms and ascarids represent the major soil-transmitted helminths (STHs) that infect humans. • Anthelmintic drugs do not offer long-term protection, so vaccines are urgently needed, but none are yet available. • A major challenge to vaccine development is the parasite's ability to modulate immunity. • The immunoregulatory prowess of STHs resides within their molecular moieties. • STH immunoregulatory molecules are being investigated as novel biologics for treating inflammatory diseases. The major soil-transmitted helminths that infect humans are the roundworms, whipworms and hookworms. Soil-transmitted helminth infections rank among the most important neglected tropical diseases in terms of morbidity, and almost one billion people are still infected with at least one species. While anthelmintic drugs are available, they do not offer long term protection against reinfection, precipitating the need for vaccines that provide long-term immunologic defense. Vaccine discovery and development is in advanced clinical development for hookworm infection, with a bivalent human hookworm vaccine in clinical trials in Brazil and Africa, but is in its infancy for both roundworm (ascariasis) and whipworm (trichuriasis) infections. One of the greatest hurdles to developing soil-transmitted helminth vaccines is the potent immunoregulatory properties of these helminths, creating a barrier to the induction of meaningful long-term protective immunity. While challenging for vaccinologists, this phenomenon presents unique opportunities to develop an entirely new class of anti-inflammatory drugs that capitalise on these immunomodulatory strategies. Epidemiologic studies and clinical trials employing experimental soil-transmitted helminth challenge models, when coupled with findings from animal models, show that at least some soil-transmitted helminth-derived molecules can protect against the onset of autoimmune, allergic and metabolic disorders, and several natural products with the desired bioactivity have been isolated and tested in pre-clinical settings. The yin and yang of soil-transmitted helminth infections reflect both the urgency for effective vaccines and the potential for new immunoregulatory molecules from parasite products. [ABSTRACT FROM AUTHOR]

Abstract: Schistosomes are parasitic blood flukes that infect approximately 200 million people and are arguably the most important human helminth in terms of mortality. The outermost surface of intra-mammalian stages of the parasite, the tegument, is the key to the parasite’s success, but it is also generally viewed as the most susceptible target for vaccines and drugs. Over the past 2 years the proteome of the Schistosoma mansoni tegument has been investigated and these studies revealed surprisingly few proteins that are predicted to be accessible to the host immune response, namely proteins with at least one membrane-spanning domain. However, of this handful of proteins, some are showing great promise as recombinant vaccines against schistosomiasis at a pre-clinical level. In particular, the tetraspanin family of integral membrane proteins appears to be abundantly represented in the tegument, and convergent data using the mouse vaccine model and correlates of protective immunity in naturally exposed people suggests that this family of membrane proteins offer great promise for schistosomiasis vaccines. With the recent advances in schistosome genomics and proteomics, a new suite of potential vaccine antigens are presented and these warrant detailed investigation and appropriate funding over the next few years. [Copyright &y& Elsevier]

Herein we show for the first time that Schistosoma mansoni adult worms secrete exosome-like extracellular vesicles ranging from 50 to 130 nm in size. Extracellular vesicles were collected from the excretory/secretory products of cultured adult flukes and purified by Optiprep density gradient, resulting in highly pure extracellular vesicle preparations as confirmed by transmission electron microscopy and Nanosight tracking analysis. Extracellular vesicle proteomic analysis showed numerous known vaccine candidates, potential virulence factors and molecules implicated in feeding. These findings provide new avenues for the exploration of host–schistosome interactions and offer a potential mechanism by which some vaccine antigens exert their protective efficacy. [ABSTRACT FROM AUTHOR]

A cDNA encoding a surface-associated antigen was cloned from an Ancylostoma caninum infective larvae (L3) cDNA library by immunoscreening with pooled human immune sera. The sera were obtained from individuals living in an Ancylostoma duodenale hookworm-endemic region of China, who had light intensity infections and high antibody titers against A. caninum L3. Ancylostoma caninum surface-associated antigen-1 is encoded by an 843 bp mRNA with a predicted open reading frame of 162 amino acids. Recombinant Ancylostoma caninum surface-associated antigen-1 was expressed in Escherichia coli and used to prepare a specific antiserum. A Western blot with anti-Ancylostoma caninum surface-associated antigen-1 specific antiserum showed that native Ancylostoma caninum surface-associated antigen-1 protein is expressed by both L3 and adult hookworms; RT-PCR confirmed that the mRNA is transcribed in both stages. In adult hookworms, the protein localised to the basal layer of the cuticle and hypodermis of adult worms. Serological analysis determined that recombinant Ancylostoma caninum surface-associated antigen-1 protein is recognised by 61% of human sera from a Necator americanus hookworm endemic area in China, indicating the antigen is immunodominant. Anti-Ancylostoma caninum surface-associated antigen-1 antiserum partially inhibited (46.7%) invasion of hookworm L3 into dog skin in vitro. Together these results suggest that Ancylostoma caninum surface-associated antigen-1 offers promise as a protective vaccine antigen. [Copyright &y& Elsevier]

The control of helminth diseases of people and livestock continues to rely on the widespread use of anti-helminthic drugs. However, concerns with the appearance of drug resistant parasites and the presence of pesticide residues in food and the environment, has given further incentive to the goal of discovering molecular vaccines against these pathogens. The exponential rate at which gene and protein sequence information is accruing for many helminth parasites requires new methods for the assimilation and analysis of the data and for the identification of molecules capable of inducing immunological protection. Some promising vaccine candidates have been discovered, in particular cathepsin L proteases from Fasciola hepatica, aminopeptidases from Haemonchus contortus, and aspartic proteases from schistosomes and hookworms, all of which are secreted into the host tissues or into the parasite intestine where they play important roles in host-parasite interactions. Since secreted proteins, in general, are exposed to the immune system of the host they represent obvious candidates at which vaccines could be targeted. Therefore, in this article, we consider the potential values and uses of algorithms for characterising cDNAs amongst the collated helminth genomic information that encode secreted proteins, and methods for their selective isolation and cloning. We also review the variety of prokaryotic and eukaryotic cell expression systems that have been employed for the production and downstream purification of recombinant proteins in functionally active form, and provide an overview of the parameters that must be considered if these recombinant proteins are to be commercialised as vaccine therapeutics in humans and/or animals. [Copyright &y& Elsevier]