Whole organism blood stage vaccines against malaria

Stanisic, Danielle I.; Good, Michael F.

doi:10.1016/j.vaccine.2015.09.057

Cited by 30 publications

(21 citation statements)

References 46 publications

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“…Although whole‐organism malaria vaccine has regained attention recently, there are still many challenges to use them in humans, including the blood transfusion adverse reactions and high dose of immunogen. Studies have indicated that the whole‐organism malaria vaccines, which will incorporate the human erythrocytes in the final vaccine products, may result in the induction of antibodies against red blood cell surface antigens (eg ABO and Rh blood group systems) . More solutions to address the blood transfusion reactions of whole‐organism malaria vaccine should be proposed in the future.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have indicated that the whole-organism malaria vaccines, which will incorporate the human erythrocytes in the final vaccine products, may result in the induction of antibodies against red blood cell surface antigens (eg ABO and Rh blood group systems). 39,40 More solutions to address the blood transfusion reactions of whole-organism malaria vaccine should be proposed in the future.…”

Section: Discussionmentioning

confidence: 99%

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Improving the immunogenicity and protective efficacy of a whole‐killed malaria blood‐stage vaccine by chloroquine

Xiao

Zhu

et al. 2019

Parasite Immunology

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A whole‐killed malaria blood‐stage vaccine (WKV) is promising in reducing the morbidity and mortality of malaria patients, but its efficacy needs to be improved. We found that the antimalarial drug chloroquine could augment the protective efficacy of the WKV of Plasmodium yoelii. The direct antimalarial effect of chloroquine on parasites during immunization could be excluded, as the administration of chloroquine or chloroquine plus alum every two weeks had a slight effect on parasitemia, and an immunization with NP‐KLH (4‐hydroxy‐3‐nitrophenylacetyl Keyhole Limpet Hemocyanin) plus chloroquine could significantly promote the generation of NP‐specific antibodies. Additionally, alum was required for chloroquine to augment the immunogenicity of the pRBC lysate. Chloroquine did not promote the parasite‐specific CD4+ T‐cell responses, but significantly enhanced the WKV‐induced germinal centre B cell reactions, class‐switch recombination and secretion of functionally protective antibodies to plasmodium. The elevated parasite‐specific antibodies were demonstrated to largely contribute to the chloroquine‐enhanced protective immunity. Thus, we report that chloroquine could be used as an adjuvant to enhance the protective immunity of WKVs through promoting humoral responses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Improving the immunogenicity and protective efficacy of a whole‐killed malaria blood‐stage vaccine by chloroquine

Xiao

Zhu

et al. 2019

Parasite Immunology

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“…Thus, both malaria parasite-specific IgG and MCP-1 in immunized serum are responsible for the suppression of parasite development in mosquitoes. Due to the failure of subunit malaria vaccines against the blood stage, whole-organism vaccines have received much attention in recent years and have been demonstrated to induce protective immunity against the blood stage (22). Vaccines against the blood stage reduce the morbidity and mortality of malaria patients; however, whether these vaccines also inhibit the development of malaria parasites in mosquitoes remains unknown.…”

Section: Mcp-1 and Parasite-specific Igg In Wkv-immunized Serum Inhibmentioning

confidence: 99%

Whole-Killed Blood-Stage Vaccine-Induced Immunity Suppresses the Development of Malaria Parasites in Mosquitoes

Zhu

Liu

Zhao

et al. 2017

The Journal of Immunology

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As a malaria transmission-blocking vaccine alone does not confer a direct benefit to the recipient, it is necessary to develop a vaccine that not only blocks malaria transmission but also protects vaccinated individuals. In this study we observed that a whole-killed blood-stage vaccine (WKV) not only conferred protection against the blood-stage challenge but also markedly inhibited the transmission of different strains of the malaria parasite. Although the parasitemia is much lower in WKV-immunized mice challenged with malaria parasites, the gametocytemia is comparable between control and immunized mice during the early stages of infection. The depletion of CD4 T cells prior to the adoptive transfer of parasites into WKV-immunized mice has no effect on the development of the malaria parasite in the mosquito, but the adoptive transfer of the serum from the immunized mice into the parasite-inoculated mice remarkably suppresses the development of malaria parasites in mosquitoes. Furthermore, immunized mice challenged with the malaria parasite generate higher levels of parasite-specific Abs and the inflammatory cytokines MCP-1 and IFN-γ. However, the adoptive transfer of parasite-specific IgG or the depletion of MCP-1, but not IFN-γ, to some extent is closely associated with the suppression of malaria parasite development in mosquitoes. These data strongly suggest that WKV-induced immune responses confer protection against the mosquito stage, which is largely dependent on malaria parasite-specific Abs and MCP-1. This finding sheds new light on blocking malaria transmission through the immunization of individuals with the WKV.

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“…Given that parasites are likely to develop resistance to newly introduced drugs, alternative strategies are required to treat malaria infections. Mass vaccination would be a better strategy, but an effective vaccine is not available, and its development remains challenging (8,9). Gaining insight into the molecular and cellular processes involved in protective immunity and pathogenesis may help in the design of an efficacious vaccine and/or immunomodulation agents to treat malaria (10,11).…”

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confidence: 99%

CD36 receptor regulates malaria-induced immune responses primarily at early blood stage infection contributing to parasitemia control and resistance to mortality

Thylur

Gowda

et al. 2017

Journal of Biological Chemistry

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In malaria, CD36 plays several roles, including mediating parasite sequestration to host organs, phagocytic clearance of parasites, and regulation of immunity. Although the functions of CD36 in parasite sequestration and phagocytosis have been clearly defined, less is known about its role in malaria immunity. Here, to understand the function of CD36 in malaria immunity, we studied parasite growth, innate and adaptive immune responses, and host survival in WT and Cd36 ؊/؊ mice infected with a non-lethal strain of Plasmodium yoelii. Compared with Cd36 ؊/؊ mice, WT mice had lower parasitemias and were resistant to death. At early but not at later stages of infection, WT mice had higher circulatory proinflammatory cytokines and lower anti-inflammatory cytokines than Cd36 ؊/؊ mice. WT mice showed higher frequencies of proinflammatory cytokineproducing and lower frequencies of anti-inflammatory cytokine-producing dendritic cells (DCs) and natural killer cells than Cd36 ؊/؊ mice. Cytokines produced by co-cultures of DCs from infected mice and ovalbumin-specific, MHC class II-restricted ␣/␤ (OT-II) T cells reflected CD36-dependent DC function. WT mice also showed increased Th1 and reduced Th2 responses compared with Cd36 ؊/؊ mice, mainly at early stages of infection. Furthermore, in infected WT mice, macrophages and neutrophils expressed higher levels of phagocytic receptors and showed enhanced phagocytosis of parasite-infected erythrocytes than those in Cd36 ؊/؊ mice in an IFN-␥-dependent manner. However, there were no differences in malaria-induced humoral responses between WT and Cd36 ؊/؊ mice. Overall, the results show that CD36 plays a significant role in controlling parasite burden by contributing to proinflammatory cytokine responses by DCs and natural killer cells, Th1 development, phagocytic receptor expression, and phagocytic activity. . 5 The abbreviations used are: DC, dendritic cell; IRBC, infected red blood cell; PfEMP1, P. falciparum erythrocyte membrane protein-1; M, macrophage; PMN, polymorphonuclear neutrophil; BMDM, M-CSF-differentiated mouse bone marrow cell; CR1/CR2, complement receptors 1 and 2Based on the results presented in Fig. 1, we predicted that CD36 contributes to malaria-induced immune responses that are involved in parasitemia control and resistance to disease Role of CD36 in malaria immunity

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Whole organism blood stage vaccines against malaria

Cited by 30 publications

References 46 publications

Improving the immunogenicity and protective efficacy of a whole‐killed malaria blood‐stage vaccine by chloroquine

Improving the immunogenicity and protective efficacy of a whole‐killed malaria blood‐stage vaccine by chloroquine

Whole-Killed Blood-Stage Vaccine-Induced Immunity Suppresses the Development of Malaria Parasites in Mosquitoes

CD36 receptor regulates malaria-induced immune responses primarily at early blood stage infection contributing to parasitemia control and resistance to mortality

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