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: 5.78). 12/1999; 180(5):1674-81. DOI: 10.1086/315059
Source: PubMed

ABSTRACT 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.

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    • "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. "
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    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 · 3.40 Impact Factor
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    • "The protection is robust with more than 90% reduction in hookworm burdens noted after larval challenge compared to non-vaccinated controls (Xiao et al, 1998b). Studies on the mechanisms of protection afforded by living L3 vaccinations reveal that antibody responses of the Th2 type are required for hookworm burden reduction (Xiao et al, 1998a; Ghosh and Hotez, 1999). However, host cellular immunity is also required with murine studies demonstrating that protection requires leukocyte adhesion, mast cell degranulation, cutaneous and subcutaneous granulomata formation , and pulmonary inflammation (Xiao et al, 1998b, 2001; Yang et al, 1998, 1999). "
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    ABSTRACT: The protective immunity elicited by ultraviolet-irradiated third-stage infective larvae of Necator americanus (UV-NaL3) and Ancylostoma caninum (UV-AcL3) was evaluated in laboratory mice (a non-permissive model) and hamsters (a permissive model). After optimizing the time of exposure to UV-irradiation, both oral and subcutaneous vaccination routes with UV-AcL3 in mice were explored. Oral vaccination was more effective at reducing the number of challenge AcL3 entering the lungs, whereas subcutaneous vaccination was more effective at blocking muscle entry. When UV-irradiated NaL3 and non-irradiated AcL3 were used as vaccines in hamsters, both of them were effective at reducing adult hookworm burdens. However, the length of protection afforded by UV-irradiated L3 was substantially greater than that resulting from immunization with non-irradiated L3. A single dose was less effective than multiple doses. The protective immunity elicited by UV-irradiated NaL3 given once every other week for a total of three immunizations was similar to that elicited by non-irradiated AcL3 given during the same schedule. Protection was not significantly affected by administering the L3 on a weekly basis for a total of three immunizations, even though the antibody titers were reduced using this schedule. These studies will facilitate the elucidation of the mechanisms underlying larval protection.
    The Southeast Asian journal of tropical medicine and public health 10/2006; 37(5):885-95. · 0.55 Impact Factor
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    • "While the precise function of these ASPs remains unknown, the secretion of ASPs also appears to be tightly coupled to the developmental biology of the larvae [14]. Previous canine trials suggest that antibody responses to these antigens may result in prevention of larval migration through tissue or attenuation of larvae such they do not mature into blood feeding adults as shown by their reduced fecundity (i.e., reduction in fecal egg counts) [17]. We sought to further elucidate the details of the humoral and especially the cellular immunological factors related to the high level of protection induced by irradiated vaccine, with special attention focused on the role of ASPs in these processes. "
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    ABSTRACT: While X-irradiated live parasites are not an acceptable proposition for human vaccination, they offer a ready experimental system to explore mechanisms by which immunity against hookworm infection may be induced in humans. As such, we sought to further elucidate the details of this highly protective immune response induced by the irradiated vaccine in canids, with special emphasis on the cellular aspects of the response. Vaccination with irradiated L3 induced high production of antibodies and strong PBMCs proliferation to crude L3 antigen preparation. Elevated IL-4 production was also observed in vaccinated dogs, especially in relation to IFN-gamma production (IL-4/IFN-gamma ratio). Serum from vaccinated animals inhibited penetration of L3 through canine skin in vitro by 60%. Finally, vaccinated animals had a strong antibody response to ASP-2, a promising vaccine antigen that is an excretory-secretory product of L3. These results add further support the idea that the Th2 immune response is required to generate protective immunity against hookworm larvae and that ES molecules released during this developmental stage are likely targets of this response.
    Vaccine 02/2006; 24(4):501-9. DOI:10.1016/j.vaccine.2005.07.091 · 3.49 Impact Factor
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