The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites

Kota Arun Kumar, Gen Ichiro Sano, Silvia Boscardin, Ruth S. Nussenzweig, Michel C. Nussenzweig, Fidel P Zavala, Victor Nussenzweig

Research output: Contribution to journalArticle

Abstract

Malaria infection starts when mosquitoes inject sporozoites into the skin. The parasites enter the blood stream and make their way to the liver where they develop into the exo-erythrocytic forms (EEFs). Immunization with irradiated sporozoites (IrSp) leads to robust protection against malaria infection in rodents, monkeys and humans by eliciting antibodies to circumsporozoite protein (CS) that inhibit sporozoite infectivity, and T cells that destroy the EEFs. To study the role of non-CS antigens in protection, we produced CS transgenic mice that were tolerant to CS T-cell epitopes. Here we show that in the absence of T-cell-dependent immune responses to CS, protection induced by immunization with two doses of IrSp was greatly reduced. Thus, although hundreds of other Plasmodium genes are expressed in sporozoites and EEFs, CS is a dominant protective antigen. Nevertheless, sterile immunity could be obtained by immunization of CS transgenics with three doses of IrSp.

Original languageEnglish (US)
Pages (from-to)937-940
Number of pages4
JournalNature
Volume444
Issue number7121
DOIs
StatePublished - Dec 14 2006

Fingerprint

Immunodominant Epitopes
Sporozoites
Proteins
Immunization
Malaria
T-Lymphocytes
Antigens
T-Lymphocyte Epitopes
Plasmodium
Infection
Culicidae
Transgenic Mice
Haplorhini
Immunity
Rodentia
Parasites
Skin
Antibodies
Liver
Genes

ASJC Scopus subject areas

  • General

Cite this

Arun Kumar, K., Sano, G. I., Boscardin, S., Nussenzweig, R. S., Nussenzweig, M. C., Zavala, F. P., & Nussenzweig, V. (2006). The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites. Nature, 444(7121), 937-940. https://doi.org/10.1038/nature05361

The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites. / Arun Kumar, Kota; Sano, Gen Ichiro; Boscardin, Silvia; Nussenzweig, Ruth S.; Nussenzweig, Michel C.; Zavala, Fidel P; Nussenzweig, Victor.

In: Nature, Vol. 444, No. 7121, 14.12.2006, p. 937-940.

Research output: Contribution to journalArticle

Arun Kumar, K, Sano, GI, Boscardin, S, Nussenzweig, RS, Nussenzweig, MC, Zavala, FP & Nussenzweig, V 2006, 'The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites', Nature, vol. 444, no. 7121, pp. 937-940. https://doi.org/10.1038/nature05361
Arun Kumar K, Sano GI, Boscardin S, Nussenzweig RS, Nussenzweig MC, Zavala FP et al. The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites. Nature. 2006 Dec 14;444(7121):937-940. https://doi.org/10.1038/nature05361
Arun Kumar, Kota ; Sano, Gen Ichiro ; Boscardin, Silvia ; Nussenzweig, Ruth S. ; Nussenzweig, Michel C. ; Zavala, Fidel P ; Nussenzweig, Victor. / The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites. In: Nature. 2006 ; Vol. 444, No. 7121. pp. 937-940.
@article{ddabae0586314768939eb3cf3eaa4ab9,
title = "The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites",
abstract = "Malaria infection starts when mosquitoes inject sporozoites into the skin. The parasites enter the blood stream and make their way to the liver where they develop into the exo-erythrocytic forms (EEFs). Immunization with irradiated sporozoites (IrSp) leads to robust protection against malaria infection in rodents, monkeys and humans by eliciting antibodies to circumsporozoite protein (CS) that inhibit sporozoite infectivity, and T cells that destroy the EEFs. To study the role of non-CS antigens in protection, we produced CS transgenic mice that were tolerant to CS T-cell epitopes. Here we show that in the absence of T-cell-dependent immune responses to CS, protection induced by immunization with two doses of IrSp was greatly reduced. Thus, although hundreds of other Plasmodium genes are expressed in sporozoites and EEFs, CS is a dominant protective antigen. Nevertheless, sterile immunity could be obtained by immunization of CS transgenics with three doses of IrSp.",
author = "{Arun Kumar}, Kota and Sano, {Gen Ichiro} and Silvia Boscardin and Nussenzweig, {Ruth S.} and Nussenzweig, {Michel C.} and Zavala, {Fidel P} and Victor Nussenzweig",
year = "2006",
month = "12",
day = "14",
doi = "10.1038/nature05361",
language = "English (US)",
volume = "444",
pages = "937--940",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7121",

}

TY - JOUR

T1 - The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites

AU - Arun Kumar, Kota

AU - Sano, Gen Ichiro

AU - Boscardin, Silvia

AU - Nussenzweig, Ruth S.

AU - Nussenzweig, Michel C.

AU - Zavala, Fidel P

AU - Nussenzweig, Victor

PY - 2006/12/14

Y1 - 2006/12/14

N2 - Malaria infection starts when mosquitoes inject sporozoites into the skin. The parasites enter the blood stream and make their way to the liver where they develop into the exo-erythrocytic forms (EEFs). Immunization with irradiated sporozoites (IrSp) leads to robust protection against malaria infection in rodents, monkeys and humans by eliciting antibodies to circumsporozoite protein (CS) that inhibit sporozoite infectivity, and T cells that destroy the EEFs. To study the role of non-CS antigens in protection, we produced CS transgenic mice that were tolerant to CS T-cell epitopes. Here we show that in the absence of T-cell-dependent immune responses to CS, protection induced by immunization with two doses of IrSp was greatly reduced. Thus, although hundreds of other Plasmodium genes are expressed in sporozoites and EEFs, CS is a dominant protective antigen. Nevertheless, sterile immunity could be obtained by immunization of CS transgenics with three doses of IrSp.

AB - Malaria infection starts when mosquitoes inject sporozoites into the skin. The parasites enter the blood stream and make their way to the liver where they develop into the exo-erythrocytic forms (EEFs). Immunization with irradiated sporozoites (IrSp) leads to robust protection against malaria infection in rodents, monkeys and humans by eliciting antibodies to circumsporozoite protein (CS) that inhibit sporozoite infectivity, and T cells that destroy the EEFs. To study the role of non-CS antigens in protection, we produced CS transgenic mice that were tolerant to CS T-cell epitopes. Here we show that in the absence of T-cell-dependent immune responses to CS, protection induced by immunization with two doses of IrSp was greatly reduced. Thus, although hundreds of other Plasmodium genes are expressed in sporozoites and EEFs, CS is a dominant protective antigen. Nevertheless, sterile immunity could be obtained by immunization of CS transgenics with three doses of IrSp.

UR - http://www.scopus.com/inward/record.url?scp=33845884017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845884017&partnerID=8YFLogxK

U2 - 10.1038/nature05361

DO - 10.1038/nature05361

M3 - Article

C2 - 17151604

AN - SCOPUS:33845884017

VL - 444

SP - 937

EP - 940

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7121

ER -