NIAID workshop on immunity to malaria: addressing immunological challenges

Augustine, Alison Deckhut; Hall, Bradford; Leitner, Wolfgang W.; Mo, Annie X.; Wali, Tonu; Fauci, Anthony S.

doi:10.1038/ni0709-673

Cited by 16 publications

(9 citation statements)

References 16 publications

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“…Similar observations have been noted in other experimental studies [23], [27], suggesting that anti-disease immunity and anti-parasite immunity act through distinct mechanisms. This notion is further supported by the observations of distinct immune mechanisms that confer immunity against severe malaria and parasitemia in adults living in endemic areas [28], [29].…”

Section: Discussionmentioning

confidence: 69%

Protection from Experimental Cerebral Malaria with a Single Dose of Radiation-Attenuated, Blood-Stage Plasmodium berghei Parasites

et al. 2011

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BackgroundWhole malaria parasites are highly effective in inducing immunity against malaria. Due to the limited success of subunit based vaccines in clinical studies, there has been a renewed interest in whole parasite-based malaria vaccines. Apart from attenuated sporozoites, there have also been efforts to use live asexual stage parasites as vaccine immunogens.Methodology and ResultsWe used radiation exposure to attenuate the highly virulent asexual blood stages of the murine malaria parasite P. berghei to a non-replicable, avirulent form. We tested the ability of the attenuated blood stage parasites to induce immunity to parasitemia and the symptoms of severe malaria disease. Depending on the mouse genetic background, a single high dose immunization without adjuvant protected mice from parasitemia and severe disease (CD1 mice) or from experimental cerebral malaria (ECM) (C57BL/6 mice). A low dose immunization did not protect against parasitemia or severe disease in either model after one or two immunizations. The protection from ECM was associated with a parasite specific antibody response and also with a lower level of splenic parasite-specific IFN-γ production, which is a mediator of ECM pathology in C57BL/6 mice. Surprisingly, there was no difference in the sequestration of CD8+ T cells and CD45+ CD11b+ macrophages in the brains of immunized, ECM-protected mice.ConclusionsThis report further demonstrates the effectiveness of a whole parasite blood-stage vaccine in inducing immunity to malaria and explicitly demonstrates its effectiveness against ECM, the most pathogenic consequence of malaria infection. This experimental model will be important to explore the formulation of whole parasite blood-stage vaccines against malaria and to investigate the immune mechanisms that mediate protection against parasitemia and cerebral malaria.

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Section: Discussionmentioning

confidence: 69%

Protection from Experimental Cerebral Malaria with a Single Dose of Radiation-Attenuated, Blood-Stage Plasmodium berghei Parasites

et al. 2011

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“…Malaria, caused by the protozoan parasites of the genus Plasmodium , is an enormous health problem in many countries of the globe with nearly half of the population is at risk (1, 2). Of several Plasmodium species that cause malaria in human, P. falciparum is the most virulent and is responsible for majority of deaths (3).…”

mentioning

confidence: 99%

Protein–DNA Complex Is the Exclusive Malaria Parasite Component That Activates Dendritic Cells and Triggers Innate Immune Responses

Gowda

Kumar

et al. 2010

The Journal of Immunology

131

193

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“…The presence of the malaria parasites in the human body elicits response from numerous immune cells. The innate immune system and the adaptive immune system form the first and the second lines of defence, respectively [14]. Adaptive immune system further provides protection against future exposures to malaria pathogens.…”

Section: Introductionmentioning

confidence: 99%

“…Adaptive immune system further provides protection against future exposures to malaria pathogens. Innate immune cells such as the Plasmodium falciparum DNA, natural killer cells (NK cells), dendritic cells (DCs), macrophages, natural killer T (NKT) cells, and T cells are involved in the clearance of circulating parasites, infected erythrocytes, and infected hepatocytes [14]. Subject to parasite strain, the DCs and NK cells may prompt or restrain inflammatory responses [15].…”

Section: Introductionmentioning

confidence: 99%

Mathematical Model for Hepatocytic-Erythrocytic Dynamics of Malaria

Orwa

Mbogo

Luboobi

2018

International Journal of Mathematics and Mathematical Sciences

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Human malaria remains a major killer disease worldwide, with nearly half (3.2 billion) of the world's population at risk of malaria infection. The infectious protozoan disease is endemic in tropical and subtropical regions, with an estimated 212 million new cases and 429,000 malaria-related deaths in 2015. An in-host mathematical model of Plasmodium falciparum malaria that describes the dynamics and interactions of malaria parasites with the host's liver cells (hepatocytic stage), the red blood cells (erythrocytic stage), and macrophages is reformulated. By a theoretical analysis, an in-host basic reproduction number 0 is derived. The disease-free equilibrium is shown to be locally and globally asymptotically stable. Sensitivity analysis reveals that the erythrocyte invasion rate , the average number of merozoites released per bursting infected erythrocyte , and the proportion of merozoites that cause secondary invasions at the blood phase are the most influential parameters in determining the malaria infection outcomes. Numerical results show that macrophages have a considerable impact in clearing infected red blood cells through phagocytosis. Moreover, the density of infected erythrocytes and hence the severity of malaria are shown to increase with increasing density of merozoites in the blood. Concurrent use of antimalarial drugs and a potential erythrocyte invasion-avoidance vaccine would minimize the density of infected erythrocytes and hence malaria disease severity.

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NIAID workshop on immunity to malaria: addressing immunological challenges

Cited by 16 publications

References 16 publications

Protection from Experimental Cerebral Malaria with a Single Dose of Radiation-Attenuated, Blood-Stage Plasmodium berghei Parasites

Protection from Experimental Cerebral Malaria with a Single Dose of Radiation-Attenuated, Blood-Stage Plasmodium berghei Parasites

Protein–DNA Complex Is the Exclusive Malaria Parasite Component That Activates Dendritic Cells and Triggers Innate Immune Responses

Mathematical Model for Hepatocytic-Erythrocytic Dynamics of Malaria

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