Antibody‐Dependent Reductions in Mouse Hookworm Burden after Vaccination with Ancylostoma caninum Secreted Protein 1

Medical Helminthology Laboratory, Department of Epidemiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 12/1999; 180(5):1674-81. DOI: 10.1086/315059
Source: PubMed


Vaccination of mice with either third-stage Ancylostoma caninum infective hookworm larvae (L3) or alum-precipitated recombinant Ancylostoma secreted protein 1 from A. caninum (Ac-ASP-1) results in protection against hookworm challenge infections. Vaccine protection is manifested by reductions in lung hookworm burdens at 48 h postchallenge. Mice actively immunized 4 times with Ac-ASP-1 also exhibited reductions in hookworm burden in the muscles. Hookworm burden reductions from Ac-ASP-1 immunization were associated with elevations in all immunoglobulin subclasses, with the greatest rise observed in host IgG1 and IgG2b. The addition of a fourth immunization resulted in even higher levels of IgG and IgE. In contrast, L3-vaccinated mice exhibited marked elevations in IgG1 and IgM, including anti-Ac-ASP-1 IgM antibody. Passive immunization with pooled sera from recombinant Ac-ASP-1-vaccinated mice also resulted in lung hookworm burden reductions. It is hypothesized that recombinant Ac-ASP-1 vaccinations elicit antibody that interferes with parasite larval migration.

1 Follower
5 Reads
  • Source
    • "Na-ASP-2 has recently been shown to induce neutrophil chemotaxis in vitro and in vivo [113], but it remains uncertain if this is a widespread property of VAL homologues [8]. The role of nematode ASPs as valid vaccine candidates has also been investigated [114]. ASPs have been suggested to have the role of allergens [34]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Teladorsagia circumcincta (order Strongylida) is an economically important parasitic nematode of small ruminants (including sheep and goats) in temperate climatic regions of the world. Improved insights into the molecular biology of this parasite could underpin alternative methods required to control this and related parasites, in order to circumvent major problems associated with anthelmintic resistance. The aims of the present study were to define the transcriptome of the adult stage of T. circumcincta and to infer the main pathways linked to molecules known to be expressed in this nematode. Since sheep develop acquired immunity against T. circumcincta, there is some potential for the development of a vaccine against this parasite. Hence, we infer excretory/secretory molecules for T. circumcincta as possible immunogens and vaccine candidates. Results A total of 407,357 ESTs were assembled yielding 39,852 putative gene sequences. Conceptual translation predicted 24,013 proteins, which were then subjected to detailed annotation which included pathway mapping of predicted proteins (including 112 excreted/secreted [ES] and 226 transmembrane peptides), domain analysis and GO annotation was carried out using InterProScan along with BLAST2GO. Further analysis was carried out for secretory signal peptides using SignalP and non-classical sec pathway using SecretomeP tools. For ES proteins, key pathways, including Fc epsilon RI, T cell receptor, and chemokine signalling as well as leukocyte transendothelial migration were inferred to be linked to immune responses, along with other pathways related to neurodegenerative diseases and infectious diseases, which warrant detailed future studies. KAAS could identify new and updated pathways like phagosome and protein processing in endoplasmic reticulum. Domain analysis for the assembled dataset revealed families of serine, cysteine and proteinase inhibitors which might represent targets for parasite intervention. InterProScan could identify GO terms pertaining to the extracellular region. Some of the important domain families identified included the SCP-like extracellular proteins which belong to the pathogenesis-related proteins (PRPs) superfamily along with C-type lectin, saposin-like proteins. The 'extracellular region' that corresponds to allergen V5/Tpx-1 related, considered important in parasite-host interactions, was also identified. Six cysteine motif (SXC1) proteins, transthyretin proteins, C-type lectins, activation-associated secreted proteins (ASPs), which could represent potential candidates for developing novel anthelmintics or vaccines were few other important findings. Of these, SXC1, protein kinase domain-containing protein, trypsin family protein, trypsin-like protease family member (TRY-1), putative major allergen and putative lipid binding protein were identified which have not been reported in the published T. circumcincta proteomics analysis. Detailed analysis of 6,058 raw EST sequences from dbEST revealed 315 putatively secreted proteins. Amongst them, C-type single domain activation associated secreted protein ASP3 precursor, activation-associated secreted proteins (ASP-like protein), cathepsin B-like cysteine protease, cathepsin L cysteine protease, cysteine protease, TransThyretin-Related and Venom-Allergen-like proteins were the key findings. Conclusions We have annotated a large dataset ESTs of T. circumcincta and undertaken detailed comparative bioinformatics analyses. The results provide a comprehensive insight into the molecular biology of this parasite and disease manifestation which provides potential focal point for future research. We identified a number of pathways responsible for immune response. This type of large-scale computational scanning could be coupled with proteomic and metabolomic studies of this parasite leading to novel therapeutic intervention and disease control strategies. We have also successfully affirmed the use of bioinformatics tools, for the study of ESTs, which could now serve as a benchmark for the development of new computational EST analysis pipelines.
    BMC Genomics 12/2012; 13(7). DOI:10.1186/1471-2164-13-S7-S10 · 3.99 Impact Factor
  • Source
    • "Excretory/secretory proteins (ESPs) of parasites enable these organisms to invade and parasitize the host cell. The ESPs can be used as immunodiagnostic, drug and vaccine candidates because several studies have shown that antibodies against ESPs protect or reduce parasite infection [52,53]. Peptide sequences that were predicted by SignalP [31] to contain a signal peptide but not contain any transmembrane regions (as predicted by Localizome [32], ProtCOMP 6.1 [33] and TMHMM 2.0 [34]), were classified as ESPs. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cryptocaryon irritans is a parasitic ciliate that causes cryptocaryonosis (white spot disease) in marine fish. Diagnosis of cryptocaryonosis often depends on the appearance of white spots on the surface of the fish, which are usually visible only during later stages of the disease. Identifying suitable biomarkers of this parasite would aid the development of diagnostic tools and control strategies for C. irritans. The C. irritans genome is virtually unexplored; therefore, we generated and analyzed expressed sequence tags (ESTs) of the parasite to identify genes that encode for surface proteins, excretory/secretory proteins and repeat-containing proteins. ESTs were generated from a cDNA library of C. irritans tomonts isolated from infected Asian sea bass, Lates calcarifer. Clustering of the 5356 ESTs produced 2659 unique transcripts (UTs) containing 1989 singletons and 670 consensi. BLAST analysis showed that 74% of the UTs had significant similarity (E-value < 10-5) to sequences that are currently available in the GenBank database, with more than 15% of the significant hits showing unknown function. Forty percent of the UTs had significant similarity to ciliates from the genera Tetrahymena and Paramecium. Comparative gene family analysis with related taxa showed that many protein families are conserved among the protozoans. Based on gene ontology annotation, functional groups were successfully assigned to 790 UTs. Genes encoding excretory/secretory proteins and membrane and membrane-associated proteins were identified because these proteins often function as antigens and are good antibody targets. A total of 481 UTs were classified as encoding membrane proteins, 54 were classified as encoding for membrane-bound proteins, and 155 were found to contain excretory/secretory protein-coding sequences. Amino acid repeat-containing proteins and GPI-anchored proteins were also identified as potential candidates for the development of diagnostic and control strategies for C. irritans. We successfully discovered and examined a large portion of the previously unexplored C. irritans transcriptome and identified potential genes for the development and validation of diagnostic and control strategies for cryptocaryonosis.
    BMC Genomics 01/2010; 11(1):76. DOI:10.1186/1471-2164-11-76 · 3.99 Impact Factor
  • Source
    • "Activation associated secreted proteins (ASPs) have been described in a wide variety of parasitic nematodes such as Ancylostoma caninum (Hawdon et al., 1996, 1999; Bin et al., 2003), Ancylostoma duodenale (Bin et al., 1999),Ancy- lostoma ceylanicum (Goud et al., 2004), Necator americanus (Bin et al., 1999; Daub et al., 2000; Asojo et al., 2005), Onchocerca volvulus (Tawe et al., 2000), Brugia malayi (Murray et al., 2001), Haemonchus contortus (Schallig and Van Leeuwen, 1997; Schallig et al., 1997a,b; Rehman and Jasmer, 1998), Cooperia punctata (Yatsuda et al., 2002) and Ostertagia ostertagi (Geldhof et al., 2003). They are of general interest as they have shown their protective capacity in multiple vaccination trials against Ancylostoma spp., H. contortus and O. ostertagi (Schallig et al., 1997a; Ghosh and Hotez, 1999; Geldhof et al., 2002, 2004; Goud et al., 2004; Meyvis et al., 2007). Three types of ASP proteins have been identified in nematodes: long ASP proteins composed of two distinct but related domains and short ASP molecules that show similarity to either the C-terminal or the N-terminal domain of the double-domain ASP. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Activation associated secreted proteins (ASP) are members of a nematode-specific protein family belonging to the SCP/Tpx-1/Ag5/PR-1/Sc7 family. Three different types of molecules have been identified in this family: two-domain ASPs and single-domain ASPs showing homology to either the C-terminal or N-terminal domain of the two-domain ASP. The function of these proteins is still unclear, but a role in transition to parasitism and a role as allergen are often suggested. Here we report that the abomasal cattle parasite Ostertagia ostertagi produces at least 15 ASPs, including two-domain and C- and N-type single-domain ASPs. Ten of these are highly transcribed in the L4 stage, whereas others are highly enriched in adult male worms. The latter was especially the case for the N-type single-domain ASPs Oo-ASP1 and Oo-ASP2 and also for Oo-ASP3, which is homologous with the Haemonchus contortus and Ancylostoma caninum C-type single-domain ASPs. Immunohistochemistry showed that Oo-ASP3 was localised in the oesophagus. Oo-ASP1 and Oo-ASP2 on the other hand were localised in the reproductive tract of both male and female worms, suggesting a role in reproduction or in the development of the reproductive tract.
    International Journal for Parasitology 04/2008; 38(3-4):455-65. DOI:10.1016/j.ijpara.2007.08.008 · 3.87 Impact Factor
Show more


5 Reads