Minimal Role for the Circumsporozoite Protein in the Induction of Sterile Immunity by Vaccination with Live Rodent Malaria Sporozoites

Mauduit, Marjorie; Tewari, Rita; Depinay, Nadya; Kayibanda, Michèle; Lallemand, Eliette; Chavatte, Jean‐Marc; Snounou, Georges; Rénia, Laurent; Grüner, Anne Charlotte

doi:10.1128/iai.01415-09

Cited by 35 publications

(38 citation statements)

References 32 publications

(40 reference statements)

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“…Previous study has shown that attenuated-sporozoite could induce the protective immunity in CSP-transgenic mice, which could not produce antibody and CD8 + T cell against CSP (Kumar et al 2006). Infection with P. berghei (P. y CSP) sporozoites, whose CSP is replaced with P. yoelii CSP, under curative cholorquine coverage, could elicit sterile immunity against sporozoite (Mauduit et al 2010). These studies strongly suggested the important role of non-CSP antigens in the protective immunity induced by the attenuated sporozoites.…”

Section: Discussionmentioning

confidence: 81%

Malaria DNA vaccine gp96NTD-CSP elicits both CSP-specific antibody and CD8+ T cell response

et al. 2015

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It is ideal for the pre-erythrocytic stage subunit vaccine to induce both CSP-specific antibody and CD8(+) T cell response. Here, we designed a novel malaria DNA vaccine gp96NTD-CSP, which was constructed by fusing the full-length of CSP with the N-terminal domain of gp96 that deleted the endoplasmic reticulum-localized motif KDEL, and investigated its protective efficacy. We found that the fusion protein gp96NTD-CSP was mainly distributed on the surface of eukaryotic cells after transfection and could be sensed as a "danger signal" by the host immune system. Interestingly, both liver parasite burden and parasitemia in mice immunized with gp96NTD-CSP were significantly lower than those in the mice immunized either with gp96NTD, CSP, or gp96NTD-SYVPSAEQI, which was constructed by fusing the CSP-specific CD8(+) T cell epitope with the N-terminal domain of gp96 deleted with KDEL. Consistently, both the level of CSP-specific antibody and the frequency of IFN-γ secreted-CSP-specific CD8(+) T cells were much higher in mice immunized with gp96NTD-CSP than those in the mice immunized either with gp96NTD, CSP, or gp96NTD-SYVPSAEQI. Our results suggest that the malaria DNA vaccine gp96NTD-CSP could induce both humoral and cellular immune responses, which is attributed to the adjuvant effect of gp96NTD and full-length CSP.

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Section: Discussionmentioning

confidence: 81%

Malaria DNA vaccine gp96NTD-CSP elicits both CSP-specific antibody and CD8+ T cell response

et al. 2015

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“…However, as described earlier, CSP-specific immunity is not absolutely necessary or sufficient to attain immunological protection against challenge (11,(21)(22)(23)(24). Thus, there is a need to identify individual immunogenic antigens so that they can be evaluated for inclusion in multicomponent subunit vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, CSP is an important but currently insufficient target for use as a single-antigen vaccine. Because responses to non-CSP antigens can protect in the absence of CSP-specific immunity in mice (11,(22)(23)(24)(25), we and others are working to discover novel protective antigens to broaden the immune repertoire.…”

mentioning

confidence: 99%

A T-cell response to a liver-stagePlasmodiumantigen is not boosted by repeated sporozoite immunizations

Murphy

Kas²,

Stone³

et al. 2013

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

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Development of an antimalarial subunit vaccine inducing protective cytotoxic T lymphocyte (CTL)-mediated immunity could pave the way for malaria eradication. Experimental immunization with sporozoites induces this type of protective response, but the extremely large number of proteins expressed by Plasmodium parasites has so far prohibited the identification of sufficient discrete T-cell antigens to develop subunit vaccines that produce sterile immunity. Here, using mice singly immunized with Plasmodium yoelii sporozoites and high-throughput screening, we identified a unique CTL response against the parasite ribosomal L3 protein. Unlike CTL responses to the circumsporozoite protein (CSP), the population of L3-specific CTLs was not expanded by multiple sporozoite immunizations. CSP is abundant in the sporozoite itself, whereas L3 expression does not increase until the liver stage. The response induced by a single immunization with sporozoites reduces the parasite load in the liver so greatly during subsequent immunizations that L3-specific responses are only generated during the primary exposure. Functional L3-specific CTLs can, however, be expanded by heterologous prime-boost regimens. Thus, although repeat sporozoite immunization expands responses to preformed antigens like CSP that are present in the sporozoite itself, this immunization strategy may not expand CTLs targeting parasite proteins that are synthesized later. Heterologous strategies may be needed to increase CTL responses across the entire spectrum of Plasmodium liver-stage proteins.

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“…For instance, the identification of additional surfaceexposed proteins could prove exceptionally useful in aiding the design of antibody-based vaccines to prevent infection by sporozoites, and thus malaria. Although CSP induces an immune response against sporozoites, recent studies have demonstrated that antibodies to other sporozoite proteins play a large role in limiting infection (78,79). Because of the medical relevance of such a finding, we chose to biotinylate putative surface-exposed sporozoite proteins on live sporozoites, enrich for them from whole parasite lysates by virtue of the tight interaction of biotin with streptavidin-conjugated Dynabeads, and then detect and identify even very low abundance proteins.…”

Section: A Selected Group Of Putative Surface-exposed Sporozoite Protmentioning

confidence: 99%

Total and Putative Surface Proteomics of Malaria Parasite Salivary Gland Sporozoites

Lindner

Swearingen

Harupa

et al. 2013

Molecular & Cellular Proteomics

178

274

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Malaria infections of mammals are initiated by the transmission of Plasmodium salivary gland sporozoites during an Anopheles mosquito vector bite. Sporozoites make their way through the skin and eventually to the liver, where they infect hepatocytes. Blocking this initial stage of infection is a promising malaria vaccine strategy. Therefore, comprehensively elucidating the protein composition of sporozoites will be invaluable in identifying novel targets for blocking infection. Previous efforts to identify the proteins expressed in Plasmodium mosquito stages were hampered by the technical difficulty of separating the parasite from its vector; without effective purifications, the large majority of proteins identified were of vector origin. Here we describe the proteomic profiling of highly purified salivary gland sporozoites from two Plasmodium species: human-infective Plasmodium falciparum and rodent-infective Plasmodium yoelii. The combination of improved sample purification and high mass accuracy mass spectrometry has facilitated the most complete proteome coverage to date for a pre-erythrocytic stage of the parasite. A total of 1991 P. falciparum sporozoite proteins and 1876 P. yoelii sporozoite proteins were identified, with >86% identified with high sequence coverage. The proteomic data were used to confirm the presence of components of three features critical for sporozoite infection of the mammalian host: the sporozoite motility and invasion apparatus (glideosome), sporozoite signaling pathways, and the contents of the apical secretory organelles. Furthermore, chemical labeling and identification of proteins on live sporozoites revealed previously uncharacterized complexity of the putative sporozoite surface-exposed proteome. Taken together, the data constitute the most comprehensive analysis to date of the protein expression of salivary gland sporozoites and reveal novel potential surface-exposed proteins that might be valuable targets for antibody blockage of infection. Molecular & Cellular

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Minimal Role for the Circumsporozoite Protein in the Induction of Sterile Immunity by Vaccination with Live Rodent Malaria Sporozoites

Abstract: Immunization with live

Cited by 35 publications

References 32 publications

Malaria DNA vaccine gp96NTD-CSP elicits both CSP-specific antibody and CD8+ T cell response

Malaria DNA vaccine gp96NTD-CSP elicits both CSP-specific antibody and CD8+ T cell response

A T-cell response to a liver-stagePlasmodiumantigen is not boosted by repeated sporozoite immunizations

Total and Putative Surface Proteomics of Malaria Parasite Salivary Gland Sporozoites

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