Specificity of Protective Immunity produced by X-irradiated Plasmodium berghei Sporozoites

Nussenzweig, Ruth S.; Vanderberg, Jerome P.; Most, Harry; Orton, Colin G.

doi:10.1038/222488a0

Cited by 137 publications

(65 citation statements)

References 12 publications

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“…Immunization of mice (1) and humans (2, 3) with irradiated sporozoites protects against sporozoite challenge but not against challenge with infected erythrocytes. The protective immunity is against the sporozoite in circulation or the parasite within hepatocytes.…”

mentioning

confidence: 99%

Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein.

Malik

Egan

Houghten

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

135

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Cytotoxic T lymphocytes (CTL) against the circumsporozoite (CS) protein of malaria sporozoites protect against malaria in rodents. Although there is interest in developing human vaccines that induce CTL against the Plasmodiumfalk4iarm CS protein, humans have never been shown to produce CTL against any Plasmodium species protein or other parasite protein. We report that when peripheral blood mononuclear cells (PBMC) from three of four volunteers immunized with irradiated P. falkiparum sporozoites were stimulated in vitro with a recombinant vaccinia virus expressing the P.fakiparum CS protein or a peptide including only amino acids 368-390 of the P. falciparum CS protein ], the PBMC lysed autologous Epstein-Barr virus-transformed B cells transfected with the P. falciparum CS protein gene or incubated with CS-(368-390) tricosapeptide. Activity was antigen specific, genetically restricted, and dependent on CD8 T cells. In one volunteer, seven peptides reflecting amino acids 311-400 were tested, and, as in B1O.BR mice, CTL activity was only associated with the CS-(368-390) peptide. Development of an assay for studying human CTL against the CS and other malaria proteins and a method for constructing target cells by direct gene transfection provide a foundation for studying the role of CTL in protection against malaria.After inoculation by mosquitoes, mature sporozoites pass through the blood to the liver where each uninucleate sporozoite can develop within a hepatocyte during -1 week to a schizont containing 1-5 x 104 uninucleate merozoites. When this schizont ruptures, each merozoite can invade an erythrocyte initiating the stage responsible for human disease.

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mentioning

confidence: 99%

Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein.

Malik

Egan

Houghten

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

135

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“…The immunity induced is strictly stage-specific since immunised mice remain fully susceptible to infected red blood cells (Nussenzweig et al, 1969), and it was considered that the same applies to immunised humans.…”

Section: The Gold Standard Of Malaria Pre-erythrocytic Stage Protectimentioning

confidence: 99%

Protective immunity against malaria liver stage after vaccination with live parasites

Rénia

2008

Parasite

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Summary :Despite nearly 100 years of research and control efforts, malaria remains one of the most important infectious diseases. An efficient vaccine would be a powerful to tool to reduce mortality and morbidity. Experimentally, induction of sterile immunity in humans after vaccination with attenuated sporozoites has been obtained. This observation has spurred the search for subunit vaccines that aim to reproduce this protection. As yet none of the current candidate subunit vaccines achieved complete protection reproducibly. This failure coupled to the recent advent of genetically modified Plasmodium parasites has led to a renewed interest in the use of live parasites for vaccination against malaria pre-erythrocytic stages. In this article, we review and discuss the recent developments in this field.

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“…Immunization of rodents (63,64) and humans (13,14,77,78) with irradiated sporozoites produces a solid immune protection. In recent studies in humans, nine of ten volunteers were protected from P. falciparum when challenged 2 weeks after the immunization regimen was completed, five of six volunteers were protected when challenged 9 months after immunization, and two of two volunteers were protected in a heterologous sporozoite challenge (21,22,29,34).…”

Section: The Malaria Problemmentioning

confidence: 99%

Malaria vaccine development

Jones

Hoffman

1994

Clin Microbiol Rev

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The malaria parasite life cycle presents several targets for attack, but these different parts of the life cycle are susceptible to different types of host immune response. For example, the sporozoite is most sensitive to immune antibody, while liver stage parasites can be eliminated by cytotoxic T lymphocytes. Attachment of merozoites to erythrocytes, on the other hand, can be blocked by antibody. Convincing experimental evidence shows that completely protective immunity to malaria can be induced. The challenge now is to design recombinant or synthetic vaccines that induce the right types of immune responses to specific life cycle stages. This requires the identification and characterization of B- and T-lymphocyte epitopes expressed by the parasite or by parasitized host cells. These epitopes must be incorporated into a delivery system that maximizes the interaction between the vaccine epitopes and the host immune system. Many epitopes from several parts of the life cycle are already characterized; development of multivalent vaccines, that is, vaccines which contain immunogens from more than one part of the life cycle, is a promising area for research efforts.

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Specificity of Protective Immunity produced by X-irradiated Plasmodium berghei Sporozoites

Cited by 137 publications

References 12 publications

Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein.

Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein.

Protective immunity against malaria liver stage after vaccination with live parasites

Malaria vaccine development

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