Asexual blood-stage malaria vaccine development: facing the challenges

Genton, Blaise; Reed, Zarifah

doi:10.1097/qco.0b013e3282dd7a29

Cited by 58 publications

(44 citation statements)

References 65 publications

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“…The failure of current blood-stage subunit vaccines is largely due to the extensive antigenic variation and polymorphisms of merozoite surface proteins (1). Recently, a whole-parasite vaccine was reported to protect against both homologous and heterologous parasite infection through the induction of a robust CD4 + T cell response.…”

Section: Discussionmentioning

confidence: 99%

“…Although great efforts have been made in the past years, there is still no effective blood-stage subunit vaccine available for malaria (1). Most of the current blood-stage subunit vaccines being developed aim to induce protective Abs against the surface proteins of the merozoite, including merozoite surface protein-1 (2), apical membrane Ag-1 (3), erythrocyte-binding Ag-175 (4), and glutamate-rich protein (5).…”

mentioning

confidence: 99%

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An Essential Role for C5aR Signaling in the Optimal Induction of a Malaria-Specific CD4+ T Cell Response by a Whole-Killed Blood-Stage Vaccine

Liu

Guo

et al. 2013

The Journal of Immunology

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The protective immunity induced by the whole-killed parasite vaccine against malarial blood-stage infection is dependent on the CD4+ T cell response. However, the mechanism underlying this robust CD4+ T cell response elicited by the whole-killed parasite vaccine is still largely unknown. In this study, we observe that immunization with Plasmodium yoelii–parasitized RBC lysate activates complement C5 and generates C5a. However, the protective efficacy against P. yoelii 17XL challenge is considerably reduced, and the malaria-specific CD4+ T cell activation and memory T cell differentiation are largely suppressed in the C5aR-deficient (C5aR−/−) mice. An adoptive transfer assay demonstrates that the reduced protection of C5aR−/− mice is closely associated with the severely impaired CD4+ T cell response. This is further confirmed by the fact that administration of C5aR antagonist significantly reduces the protective efficacy of the immunized B cell–deficient mice. Further study indicates that the defective CD4+ T cell response in C5aR−/− mice is unlikely involved in the expansion of CD4+CD25+Foxp3+ T cells, but strongly linked to a defect in dendritic cell (DC) maturation and the ability to allostimulate CD4+ T cells. These results demonstrate that C5aR signaling is essential for the optimal induction of the malaria-specific CD4+ T cell response by the whole-killed parasite vaccine through modulation of DCs function, which provides us with new clues to design an effective blood-stage subunit vaccine and helps us to understand the mechanism by which the T cell response is regulated by the complement system.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

An Essential Role for C5aR Signaling in the Optimal Induction of a Malaria-Specific CD4+ T Cell Response by a Whole-Killed Blood-Stage Vaccine

Liu

Guo

et al. 2013

The Journal of Immunology

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“…Several MSP-1 based vaccines are at various phases of pre-clinical or clinical development of which FMP1 (falciparum malaria protein-1) 6,8,9 that comprises of MSP-1 42 (3D7) formulated with adjuvant, ASO2A, (GlaxoSmithKline, Belgium) is at the most advanced stage. FMP1 has induced significant growth inhibitory antibodies.…”

Section: Why Should Blood Stage Antigens Be a Component Of A Malaria mentioning

confidence: 99%

“…FMP1 has induced significant growth inhibitory antibodies. 6,8,9 This vaccine has been developed by Walter Reed Army Institute of Research (WRAIR, USA) and GlaxoSmithKline through funding from MVI/PATH (Malaria Vaccine Initiative/ Program for Appropriate Technology in Health). While, the safety and immunogenicity of FMP1 was confirmed in Phase I trials, 16 a Phase II efficacy trial among young Kenyan children failed to elicit any protection.…”

Section: Why Should Blood Stage Antigens Be a Component Of A Malaria mentioning

confidence: 99%

Malaria vaccine development based on merozoite surface proteins ofPlasmodium falciparum

Chauhan¹,

Yazdani²,

Gaur³

2010

Human Vaccines

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“…Many preliminary vaccines have been based on the P. falciparum circumsporozoite surface antigen, circumsporozoite protein, or its epitopes because immune response of the body generally targets this protein when mounting an attack on the parasite [11]. The most promising being the demonstration that non immune volunteers repeatedly challenged and cured with pre-erythrocytic-stage parasites developed immunity to subsequent challenge as well as the demonstration of the efficacy of the first liver-stage vaccine tested in a malaria endemic area to reduce parasite density in children [12,13].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Immune Response in Mouse Blood Post Injection with Gamma Ray-Attenuated Sporozoites of Plasmodium berghei

Syaifudin¹,

Darlina²,

Rahardjo³

et al. 2014

UCMS

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Abstract:Ionizing radiation has been successfully used to attenuate parasites for malaria vaccine development. To get a deeper insight in the immune response post injection of irradiated pre-erythrocytic stage of malaria parasites (sporozoites), we used Plasmodium berghei as a model. Anopheles sp. with infective parasites in their salivary glands was irradiated with 0-225 Gy of gamma rays. The isolated sporozoites were intravenously injected into groups of mouse followed by a booster and challenge in interval time of 2-4 weeks. The detection of parasite in the infected mosquito was done with nested-PCR (polymerase chain reaction). Immune response in mouse blood was examined with ELISA (enzime-linked immunosorbent assay) and protein profile of irradiated sporozoites was studied with SDS-PAGE (sodium dodecyl sulphate-polyacrylamide gel electrophoresis). By using Anopheles farauti as the more susceptible mosquito to parasite infection, based on molecular detection and parasites observation in mouse blood, there was low or no effect of irradiated sporozoites on the immune responses in mouse serum. Some factors affecting these results are discussed. There was a slight alteration of protein profile of sporozoite infected salivary glands post gamma ray irradiation except for its band intensity, indicating the low effectiveness of gamma irradiation at optimal dose. It can be concluded that irradiated sporozoite as vaccine materials was failed in eliciting immune response.

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Asexual blood-stage malaria vaccine development: facing the challenges

Cited by 58 publications

References 65 publications

An Essential Role for C5aR Signaling in the Optimal Induction of a Malaria-Specific CD4+ T Cell Response by a Whole-Killed Blood-Stage Vaccine

An Essential Role for C5aR Signaling in the Optimal Induction of a Malaria-Specific CD4+ T Cell Response by a Whole-Killed Blood-Stage Vaccine

Malaria vaccine development based on merozoite surface proteins ofPlasmodium falciparum

Evaluation of Immune Response in Mouse Blood Post Injection with Gamma Ray-Attenuated Sporozoites of Plasmodium berghei

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