Successful vaccination of BALB/c mice against human hookworm (Necator americanus): the immunological phenotype of the protective response

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Girod, N., Brown, A., Pritchard, D.I. and Billett, E.E. ORCID: 0000-0001-8245-6519, 2003. Successful vaccination of BALB/c mice against human hookworm (Necator americanus): the immunological phenotype of the protective response. International Journal for Parasitology, 33 (1), pp. 71-80. ISSN 0020-7519

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Abstract

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 γ-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 IL-4 relative to γ-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/γ-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.

Item Type:

Journal article

Publication Title:

International Journal for Parasitology

Creators:

Girod, N., Brown, A., Pritchard, D.I. and Billett, E.E.

Publisher:

Elsevier (not including Cell Press)

Place of Publication:

Oxford

Date:

2003