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

P.A. Frost; P.S. Coulson; M. Eberl; J.A.M. Langermans; R.A. Vervenne; G.J. Van Dam; A.M. Deelder; A.W. Thomas; R.A. Wilson

doi:10.1128/IAI.69.9.5352–5362.2001

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

P.A. Frost, P.S. Coulson, M. Eberl, J.A.M. Langermans, R.A. Vervenne, G.J. Van Dam, A.M. Deelder, A.W. Thomas, R.A. Wilson

Biology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	5352-5362
Number of pages	10
Journal	Infection and Immunity
Volume	69
Issue number	9
DOIs	https://doi.org/10.1128/IAI.69.9.5352–5362.2001
Publication status	Published - Sep 2001

Bibliographical note

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

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Cite this

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., & Wilson, R. A. (2001). Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees. Infection and Immunity, 69(9), 5352-5362. https://doi.org/10.1128/IAI.69.9.5352–5362.2001

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

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.",

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",

author = "P.A. Frost and P.S. Coulson and M. Eberl and J.A.M. Langermans and R.A. Vervenne and {Van Dam}, G.J. and A.M. Deelder and A.W. Thomas and R.A. Wilson",

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month = sep,

doi = "10.1128/IAI.69.9.5352–5362.2001",

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T1 - Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees

AU - Frost, P.A.

AU - Coulson, P.S.

AU - Eberl, M.

AU - Langermans, J.A.M.

AU - Vervenne, R.A.

AU - Van Dam, G.J.

AU - Deelder, A.M.

AU - Thomas, A.W.

AU - Wilson, R.A.

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N2 - 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.

AB - 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.

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KW - ADULT WORM ANTIGENS

KW - LUNG-STAGE LARVAE

KW - CYTOKINE PRODUCTION

KW - MONOCLONAL-ANTIBODIES

KW - PARASITIC INFECTIONS

KW - RECOMBINANT ANTIGEN

KW - MANSONI INFECTIONS

KW - INTERFERON-GAMMA

U2 - 10.1128/IAI.69.9.5352–5362.2001

DO - 10.1128/IAI.69.9.5352–5362.2001

M3 - Article

VL - 69

SP - 5352

EP - 5362

JO - Infection and Immunity

JF - Infection and Immunity

SN - 1098-5522

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ER -