Effect of combining the larval antigens Ancylostoma secreted protein 2 (ASP-2) and metalloprotease 1 (MTP-1) in protecting hamsters against hookworm infection and disease caused by Ancylostoma ceylanicum

Méndez, Susana; Zhan, Bin; Goud, Gaddam Narsa; Ghosh, Kashinath; Dobardzic, Azra; Wu, Wenhui; Liu, Sen; Deumic, Vehid; Dobardzic, R.; Liu, Yueyuan; Bethony, Jeff; Hotez, Peter J.

doi:10.1016/j.vaccine.2004.12.022

Cited by 75 publications

(58 citation statements)

References 17 publications

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“…Our data suggest that ASP-2 is also central to promote tissue migration in the host. This could also provide the basis by which anti-ASP-2 antibodies are protective against larval challenge infections (Goud et al, 2004;Mendez et al, 2005). Our results also confirm that the mechanisms of action of the two larval proteins are different, since only ASP-2 promoted neutrophil migration.…”

Section: Discussionsupporting

confidence: 76%

“…Our results also confirm that the mechanisms of action of the two larval proteins are different, since only ASP-2 promoted neutrophil migration. Na-ASP-2 has been selected as a vaccine candidate based on human immuno-epidemiologic studies and laboratory animal vaccine trials Goud et al, 2004;Hotez et al, 2003;Mendez et al, 2005). In order to clarify the role of Na-ASP-2 as a functional vaccine, and in an attempt to unravel its function, structural studies were carried out .…”

Section: Discussionmentioning

confidence: 99%

“…On the basis of in vitro data, animal trials and human epidemiological studies Goud et al, 2004;Hotez et al, 2003;Mendez et al, 2005), the L3-secreted N. americanus ASP-2 (Na-ASP-2) was selected as a vaccine antigen to undergo further development . As mentioned above, ASP-2 is released by the L3 after invading the host and it is likely to play a role in the transition to parasitism (Hotez et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Bower¹,

Constant²,

Méndez³

2008

Experimental Parasitology

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The L3-secreted Ancylostoma Secreted Protein-2 from the human hookworm Necator americanus (Na-ASP-2) has been selected as a candidate vaccine antigen in anticipation of clinical trials. Its crystal structure revealed that Na-ASP-2 has structural and charge similarities to CC-chemokines, suggesting that it might act as a chemokine mimic when released by the infective larvae during tissue migration. Using the air pouch model of acute inflammation, we found that Na-ASP-2 induced a significant leukocyte influx to the skin pouch, mostly comprised of neutrophils (60%) and monocytes (30%) that was transient and resolved in 24 h. Other hookworm larval proteins did not cause any inflammatory leukocytes to migrate into air pouches. In vitro chemotaxis assays confirmed our results and demonstrated that leukocyte migration was a direct effect of Na-ASP-2 exposure and not caused by other molecules released by host cells in the inflammatory microenvironment or by the expression vector.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Bower¹,

Constant²,

Méndez³

2008

Experimental Parasitology

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“…ASPs belong to a group of evolutionary related secreted proteins called the SCP/tpx-1/Ag5/PR-1/Sc7 www.elsevier.com/locate/vetpar Veterinary Parasitology 149 (2007) [239][240][241][242][243][244][245] family and are present in different organisms such as plants, mammals and nematodes. ASP molecules have previously shown their protective capacity in vaccine trials against Ancylostoma caninum (Ghosh et al, 1996;Ghosh and Hotez, 1999;Sen et al, 2000), A. ceylanicum (Goud et al, 2004;Mendez et al, 2005), Onchocerca volvulus (MacDonald et al, 2004) and Haemonchus contortus (Schallig et al, 1997a,b;Vervelde et al, 2002). The exact function of the ASPs remains unclear, although it is believed that they play a role in parasite infection and transition to parasitism .…”

Section: Introductionmentioning

confidence: 99%

Vaccination against Ostertagia ostertagi with subfractions of the protective ES-thiol fraction

Meyvis¹,

Geldhof²,

Gevaert³

et al. 2007

Veterinary Parasitology

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Previous vaccination trials against Ostertagia ostertagi in cattle have demonstrated the protective capacity of a protein fraction termed ES-thiol, which is enriched for activation-associated secreted proteins (ASPs) and cysteine proteases. In this study, ES-thiol was subfractionated through Q-Sepharose anion exchange chromatography to determine whether the ASPs and/or the cysteine proteases are responsible for the induced protection. Calves (seven/group) were immunized three times intramuscularly with 100 mg of ES-thiol or equivalent amounts of an ASP-enriched fraction, a cysteine protease-enriched fraction or a rest fraction, with QuilA adjuvant. A negative control group only received QuilA. After the final immunization the animals were challenged with a trickle infection of 25,000 infectious L3 larvae (1000 L3/day; 5 days/week). During a 2-month period the geometric mean cumulative faecal egg count (FEC) of the ES-thiol group was reduced by 62% compared to the QuilA control group (P < 0.05). Groups injected with the ASP-enriched, the cysteine protease-enriched and the rest fraction demonstrated a reduction in cumulative FEC of 74, 80 and 70%, respectively (P < 0.01). Although no significant reductions in worm burdens were observed, adult male and female worms were significantly smaller in all vaccinated groups (P < 0.05), except for male worms from the ES-thiol group. These results suggest the protective capacity of ASPs and the presence of other protective antigens in the ES-thiol fraction. #

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“…However, gut associated metalloproteases are not the only class of hookworms metalloproteases. Hookworms express astacin like metalloproteases (Zhan et al 2002;Mendez et al 2005;Feng et al 2007;Bąska et al 2013). Immunization with Ace-MTP-1 and Ac-MTP-1 resulted in no statistical significant worm burden reduction but diminished fecal egg count was observed after immunization with Ace-MTP-1 .…”

Section: Discussionmentioning

confidence: 98%

Ancylostoma ceylanicum metalloprotease 6 DNA vaccination induces partial protection against hookworm challenge infection

Wiśniewski

Jaros

Bąska

et al. 2013

Acta Parasitologica

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Hookworms are blood feeding intestinal nematodes that infect more than 500 million people and cause iron deficiency anemia. Infected children suffer from physical and cognitive growth retardation. Because of potential anthelminthic drug resistance, the need for vaccine development is urgent. Numerous antigens have been tested in animal models as vaccines against hookworm infection, but there is no effective human vaccine. We cloned a cDNA encoding Ancylostoma ceylanicum metalloprotease 6 (Acemep-6). Ace-MEP-6 is a protein with a predicted molecular mass of 101.87 kDa and based on computational analysis it is very likely to be engaged in food processing via hemoglobin digestion. Groups of hamsters were immunized with an Ace-mep-6 cDNA vaccine, either once or three times. Animals that were administered one dose developed high resistance (80%, p < 0.01) against challenge infection, whereas triple immunization resulted in no worm burden reduction. These results suggest that DNA vaccines can be powerful tools in ancylostomiasis control, although the mechanisms through which protection is conferred remain unclear.

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Effect of combining the larval antigens Ancylostoma secreted protein 2 (ASP-2) and metalloprotease 1 (MTP-1) in protecting hamsters against hookworm infection and disease caused by Ancylostoma ceylanicum

Cited by 75 publications

References 17 publications

Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Vaccination against Ostertagia ostertagi with subfractions of the protective ES-thiol fraction

Ancylostoma ceylanicum metalloprotease 6 DNA vaccination induces partial protection against hookworm challenge infection

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