Plasmodium berghei sporozoite challenge of vaccinated BALB/c mice leads to the induction of humoral immunity and improved function of CD8(+) memory T cells

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Plasmodium berghei sporozoite challenge of vaccinated BALB/c mice leads to the induction of humoral immunity and improved function of CD8(+) memory T cells. / Tartz, Susanne; Deschermeier, Christina; Retzlaff, Silke; Heussler, Volker; Sebo, Peter; Fleischer, Bernhard; Jacobs, Thomas.

In: EUR J IMMUNOL, Vol. 43, No. 3, 01.03.2013, p. 693-704.

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@article{e814fc4a7ecb4e15bdc685276b2db933,
title = "Plasmodium berghei sporozoite challenge of vaccinated BALB/c mice leads to the induction of humoral immunity and improved function of CD8(+) memory T cells",
abstract = "Protection against malaria can be achieved by induction of a strong CD8(+) T-cell response against the Plasmodium circumsporozoite protein (CSP), but most subunit vaccines suffer from insufficient memory responses. In the present study, we analyzed the impact of postimmunization sporozoite challenge on the development of long-lasting immunity. BALB/c mice were immunized by a heterologous prime/boost regimen against Plasmodium berghei CSP that induces a strong CD8(+) T-cell response and sterile protection, which is short-lived. Here, we show that protective immunity is prolonged by a sporozoite challenge after immunization. Repeated challenges induced sporozoite-specific antibodies that showed protective capacity. The numbers of CSP-specific CD8(+) T cells were not substantially enhanced by sporozoite infections; however, CSP-specific memory CD8(+) T cells of challenged mice displayed a higher cytotoxic activity than memory T cells of immunized-only mice. CD4(+) T cells contributed to protection as well; but CD8(+) memory T cells were found to be the central mediator of sterile protection. Based on these data, we suggest that prolonged protective immunity observed after immunization and infection is composed of different antiparasitic mechanisms including CD8(+) effector-memory T cells with increased cytotoxic activity as well as CD4(+) memory T cells and neutralizing antibodies.",
keywords = "Animals, Antibodies, Protozoan, Antibody Specificity, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Disease Models, Animal, Female, Immunity, Humoral, Immunization, Immunologic Memory, Malaria, Malaria Vaccines, Mice, Mice, Inbred BALB C, Phenotype, Plasmodium berghei, Sporozoites",
author = "Susanne Tartz and Christina Deschermeier and Silke Retzlaff and Volker Heussler and Peter Sebo and Bernhard Fleischer and Thomas Jacobs",
note = "{\textcopyright} 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2013",
month = mar,
day = "1",
doi = "10.1002/eji.201142262",
language = "English",
volume = "43",
pages = "693--704",
journal = "EUR J IMMUNOL",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag GmbH",
number = "3",

}

RIS

TY - JOUR

T1 - Plasmodium berghei sporozoite challenge of vaccinated BALB/c mice leads to the induction of humoral immunity and improved function of CD8(+) memory T cells

AU - Tartz, Susanne

AU - Deschermeier, Christina

AU - Retzlaff, Silke

AU - Heussler, Volker

AU - Sebo, Peter

AU - Fleischer, Bernhard

AU - Jacobs, Thomas

N1 - © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Protection against malaria can be achieved by induction of a strong CD8(+) T-cell response against the Plasmodium circumsporozoite protein (CSP), but most subunit vaccines suffer from insufficient memory responses. In the present study, we analyzed the impact of postimmunization sporozoite challenge on the development of long-lasting immunity. BALB/c mice were immunized by a heterologous prime/boost regimen against Plasmodium berghei CSP that induces a strong CD8(+) T-cell response and sterile protection, which is short-lived. Here, we show that protective immunity is prolonged by a sporozoite challenge after immunization. Repeated challenges induced sporozoite-specific antibodies that showed protective capacity. The numbers of CSP-specific CD8(+) T cells were not substantially enhanced by sporozoite infections; however, CSP-specific memory CD8(+) T cells of challenged mice displayed a higher cytotoxic activity than memory T cells of immunized-only mice. CD4(+) T cells contributed to protection as well; but CD8(+) memory T cells were found to be the central mediator of sterile protection. Based on these data, we suggest that prolonged protective immunity observed after immunization and infection is composed of different antiparasitic mechanisms including CD8(+) effector-memory T cells with increased cytotoxic activity as well as CD4(+) memory T cells and neutralizing antibodies.

AB - Protection against malaria can be achieved by induction of a strong CD8(+) T-cell response against the Plasmodium circumsporozoite protein (CSP), but most subunit vaccines suffer from insufficient memory responses. In the present study, we analyzed the impact of postimmunization sporozoite challenge on the development of long-lasting immunity. BALB/c mice were immunized by a heterologous prime/boost regimen against Plasmodium berghei CSP that induces a strong CD8(+) T-cell response and sterile protection, which is short-lived. Here, we show that protective immunity is prolonged by a sporozoite challenge after immunization. Repeated challenges induced sporozoite-specific antibodies that showed protective capacity. The numbers of CSP-specific CD8(+) T cells were not substantially enhanced by sporozoite infections; however, CSP-specific memory CD8(+) T cells of challenged mice displayed a higher cytotoxic activity than memory T cells of immunized-only mice. CD4(+) T cells contributed to protection as well; but CD8(+) memory T cells were found to be the central mediator of sterile protection. Based on these data, we suggest that prolonged protective immunity observed after immunization and infection is composed of different antiparasitic mechanisms including CD8(+) effector-memory T cells with increased cytotoxic activity as well as CD4(+) memory T cells and neutralizing antibodies.

KW - Animals

KW - Antibodies, Protozoan

KW - Antibody Specificity

KW - CD4-Positive T-Lymphocytes

KW - CD8-Positive T-Lymphocytes

KW - Disease Models, Animal

KW - Female

KW - Immunity, Humoral

KW - Immunization

KW - Immunologic Memory

KW - Malaria

KW - Malaria Vaccines

KW - Mice

KW - Mice, Inbred BALB C

KW - Phenotype

KW - Plasmodium berghei

KW - Sporozoites

U2 - 10.1002/eji.201142262

DO - 10.1002/eji.201142262

M3 - SCORING: Journal article

C2 - 23229763

VL - 43

SP - 693

EP - 704

JO - EUR J IMMUNOL

JF - EUR J IMMUNOL

SN - 0014-2980

IS - 3

ER -