Successful vaccination of BALB/c mice against human hookworm (Necator americanus): the immunological phenotype of the protective response.
In this murine (BALB/c) model of necatoriasis, high levels of protection against challenge infection by Necator americanus larvae (n=300) were afforded by successive vaccinations at 14-day intervals, either subcutaneously or percutaneously, with gamma-irradiated N. americanus larvae (n=300). Percutaneous vaccination was significantly more effective than the subcutaneous route, with pulmonary larval burdens at 3 days post-infection being reduced by 97.8 vs. 89.3%, respectively, after three immunisations (P<0.05). No worms were recovered from the intestines of thrice vaccinated mice. Two percutaneous vaccinations also reduced worm burdens, by 57% in the lungs and 98% in the intestines; P<0.05. In vaccinated animals, lung pathology (mainly haemorrhage) following infection was greatly reduced compared with non-vaccinated animals. In vaccinated mice (but not in non-vaccinated mice) mast cells accumulated in the skin and were degranulated. RT-PCR analyses of mRNAs in the skin of vaccinated animals indicated increased expression of interleukin (IL)-4 relative to gamma-interferon (gamma-IFN). Lymphocytes from the axillary (skin-draining) lymph nodes of vaccinated mice, stimulated in vitro with concanavalin A, exhibited enhanced secretion of IL-4 protein and a higher IL-4/gamma-IFN protein ratio than lymphocytes from non-vaccinated animals. In vaccinated mice, levels of IgG1 and IgG3 (directed against larval excretory/secretory products) were elevated for the most part compared with those in non-vaccinated animals. These data demonstrate the successful vaccination of BALB/c mice against human hookworm infection and suggest that a localised Th2 response may be important for conferring protection against necatoriasis.
Girod
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N
Department of Life Sciences, Faculty of Science, The Nottingham Trent University, Clifton Lane, UK.
Brown
A
A
Pritchard
D I
DI
Billett
E E
EE
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000947:Antigens, Helminth / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007422:Intestines / Q000469:parasitology; D008168:Lung / Q000469:parasitology; D008297:Male; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D017221:Necator americanus / Q000276:immunology*; D009332:Necatoriasis / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D012867:Skin / Q000469:parasitology; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000276:immunology*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; D015847:Interleukin-4; D007371:Interferon-gamma