Protective Immunity Produced by the Injection of X-Irradiated Sporozoites of Plasmodium berghei

Vanderberg, Jerome P.; Nussenzweig, R S; Most, Harry

doi:10.1093/milmed/134.9.1183

Cited by 162 publications

(67 citation statements)

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“…This stepwise accumulation (or loss) of single base changes suggests that variation is introduced gradually throughout the repeated region, and in a directional manner. It would be of interest to determine whether the repeats of other antigenically related rodent CS proteins (such as those of Plasmodium chabaudi and Plasmodium vinkei [30]) exhibit the same or a similar pattern of change.…”

Section: Discussionmentioning

confidence: 99%

Circumsporozoite protein of Plasmodium berghei: gene cloning and identification of the immunodominant epitopes.

Eichinger¹,

Arnot²,

Tam³

et al. 1986

Mol. Cell. Biol.

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The gene encoding the circumsporozoite (CS) protein of the rodent malaria parasite Plasmodium berghei was cloned and characterized. A cDNA library made from P. berghei sporozoite RNA was screened with a monoclonal antibody for expression of CS protein epitopes. The resulting cDNA clone was used to isolate the CS protein gene from a lambda library containing parasite blood-stage DNA. The CS protein gene contains a central region encoding two types of tandemly repeated amino acid units, flanked by nonrepeated regions encoding amino-and carboxy-terminal signal and anchorlike sequences, respectively. One of the central repeated amino acid unit types contains the immunodominant epitopes.The sporozoite stage of malaria parasites carries a protein on its outer surface (1) which expresses a unique immunodominant epitope recognized by immunized or repeatedly infected hosts (33,34). Sera from mice immunized with Plasmodium berghei sporozoites immunoprecipitate a single 44,O000Mr protein, the circumsporozoite (CS) protein, from extracts of surface-labeled sporozoites (33). Immunoprecipitation of extracts of metabolically labeled sporozoites with a monoclonal antibody (3D11) directed to the CS protein demonstrated that the 44,000Mr membrane form is derived from a 54,000-Mr intracellular precursor (33). The CS protein from monkey and human malaria parasites contains aminoand carboxy-terminal regions of relatively low immunogenicity which flank a central region of highly immunogenic, tandemly repeated amino acid units, the sequences of which differ from species to species (2, 3, 6, 22). Monoclonal antibodies to the repeated amino acid units neutralize parasite infectivity (20,21), suggesting that CS proteins might be useful as sporozoite-stage vaccines. The recent isolation of the CS protein genes from species of malaria parasites which infect humans has made possible the production of the large amounts of antigen necessary for testing its immunoprophylactic value (10,17,35). However, an easily manipulated animal model system is required for studying the mechanisms of protective immunity and the role of the CS protein during the initial stage of parasite infection.Here we describe the isolation of the CS protein gene of the rodent parasite P. berghei, the complete nucleotide sequence, and the identification of the epitope-encoding region. [35S]methionine, and 32P-labeled deoxynucleoside triphosphates were from Amersham Corp., Arlington Heights, Ill. MATERIALSAntibodies. Monoclonal antibodies 3D11 and 4G1 and goat anti-mouse immunoglobulin were used as purified immunoglobulin G fractions. Precipitation of immune complexes (13) was performed with protein A-Sephadex (Pharmacia Fine Chemicals, Piscataway, N.J.). Antibodies were radiolabeled with 125I by using lodogen (Pierce Chemical Co., Rockford, Ill.) according to the instructions of the manufacturers.Immunoassays. A two-site immunoradiometric assay (IRMA) was performed as described in reference 34. Flexible microtiter plates (Becton Dickinson Labware, Oxnard, Calif.) were coa...

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Section: Discussionmentioning

confidence: 99%

Circumsporozoite protein of Plasmodium berghei: gene cloning and identification of the immunodominant epitopes.

Eichinger¹,

Arnot²,

Tam³

et al. 1986

Mol. Cell. Biol.

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“…Some protection (50%; n ϭ 6) was observed in mice that received 250 sporozoites incubated with sera from C/C-or FϩC/MϩC-immunized mice, but infection in control mice was inconsistent (33%; n ϭ 6). Adding anti-CSP antibody to sporozoites cross-links the CSP and causes shedding of the protein, a process termed the CSP precipitation reaction (43). It is possible this phenomenon occurs during the incubation period in vitro, leading to loss of the anti-CS antibodies, without which sporozoites evade clearance through Fc-mediated phagocytosis and complement activation (39).…”

Section: Antibodies Induced By C/c and F؉c/m؉c Immunization Do Not DImentioning

confidence: 99%

Combination of Protein and Viral Vaccines Induces Potent Cellular and Humoral Immune Responses and Enhanced Protection from Murine Malaria Challenge

Hutchings

Birkett²,

Moore

et al. 2007

Infect Immun

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The search for an efficacious vaccine against malaria is ongoing, and it is now widely believed that to confer protection a vaccine must induce very strong cellular and humoral immunity concurrently. We studied the immune response in mice immunized with the recombinant viral vaccines fowlpox strain FP9 and modified virus Ankara (MVA), a protein vaccine (CV-1866), or a combination of the two; all vaccines express parts of the same preerythrocytic malaria antigen, the Plasmodium berghei circumsporozoite protein (CSP). Mice were then challenged with P. berghei sporozoites to determine the protective efficacies of different vaccine regimens. Two immunizations with the protein vaccine CV-1866, based on the hepatitis B core antigen particle, induced strong humoral immunity to the repeat region of CSP that was weakly protective against sporozoite challenge. Prime-boost with the viral vector vaccines, FP9 followed by MVA, induced strong T-cell immunity to the CD8 ؉ epitope Pb9 and partially protected animals from challenge. Physically mixing CV-1866 with FP9 or MVA and then immunizing with the resultant combinations in a prime-boost regimen induced both cellular and humoral immunity and afforded substantially higher levels of protection (combination, 90%) than either vaccine alone (CV-1866, 12%; FP9/MVA, 37%). For diseases such as malaria in which different potent immune responses are required to protect against different stages, using combinations of partially effective vaccines may offer a more rapid route to achieving deployable levels of efficacy than individual vaccine strategies.

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“…When cross-linked by anti-repeat Abs, CS protein is shed as a long precipitate at the posterior end of the parasite, termed the circumsporozoite precipitin (CSP) reaction (16). The CS(Pf) sporozoites gave positive CSP reactions when incubated with mAb 2A10, but not mAb 3D11 (Fig.…”

Section: Immunological Properties Of the Cs(pf) Parasitesmentioning

confidence: 99%

Cutting Edge: A New Tool to Evaluate Human Pre-Erythrocytic Malaria Vaccines: Rodent Parasites Bearing a HybridPlasmodium falciparumCircumsporozoite Protein

Persson¹,

Oliveira

Sultan³

et al. 2002

The Journal of Immunology

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Malaria vaccines containing the Plasmodium falciparum Circumsporozoite protein repeat domain are undergoing human trials. There is no simple method to evaluate the effect of vaccine-induced responses on P. falciparum sporozoite infectivity. Unlike the rodent malaria Plasmodium berghei, P. falciparum sporozoites do not infect common laboratory animals and only develop in vitro in human hepatocyte cultures. We generated a recombinant P. berghei parasite bearing P. falciparum Circumsporozoite protein repeats. These hybrid sporozoites are fully infective in vivo and in vitro. Monoclonal and polyclonal Abs to P. falciparum repeats neutralize hybrid parasite infectivity, and mice immunized with a P. falciparum vaccine are protected against challenge with hybrid sporozoites.

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Protective Immunity Produced by the Injection of X-Irradiated Sporozoites of Plasmodium berghei

Cited by 162 publications

References 0 publications

Circumsporozoite protein of Plasmodium berghei: gene cloning and identification of the immunodominant epitopes.

Circumsporozoite protein of Plasmodium berghei: gene cloning and identification of the immunodominant epitopes.

Combination of Protein and Viral Vaccines Induces Potent Cellular and Humoral Immune Responses and Enhanced Protection from Murine Malaria Challenge

Cutting Edge: A New Tool to Evaluate Human Pre-Erythrocytic Malaria Vaccines: Rodent Parasites Bearing a HybridPlasmodium falciparumCircumsporozoite Protein

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