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Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees

Frost, P.A., Coulson, P.S., Eberl, M., Langermans, J.A.M., Vervenne, R.A., Van Dam, G.J., Deelder, A.M., Thomas, A.W. and Wilson, R.A. (2001) Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees. Infection and Immunity. pp. 5352-5362. ISSN 1098-5522

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Abstract

The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection.

Item Type: Article
Copyright, Publisher and Additional Information: Copyright © 2001, American Society for Microbiology. All Rights Reserved
Keywords: IRRADIATED CERCARIA VACCINE, BLOOD MONONUCLEAR-CELLS, ADULT WORM ANTIGENS, LUNG-STAGE LARVAE, CYTOKINE PRODUCTION, MONOCLONAL-ANTIBODIES, PARASITIC INFECTIONS, RECOMBINANT ANTIGEN, MANSONI INFECTIONS, INTERFERON-GAMMA
Academic Units: The University of York > Biology (York)
Depositing User: Sherpa Assistant
Date Deposited: 04 Mar 2005
Last Modified: 17 Oct 2013 14:37
Published Version: http://dx.doi.org/10.1128/IAI.69.9.5352–5362.2001
Status: Published
Refereed: Yes
Related URLs:
URI: http://eprints.whiterose.ac.uk/id/eprint/332

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