The malaria vaccine: anti-parasite or anti-disease?

Playfair, John; Taverne, Janice; Bate, Clive; Souza, J. Brian de

doi:10.1016/0167-5699(90)90007-v

Cited by 152 publications

(59 citation statements)

References 19 publications

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“…IgM antibodies against PI may block parasite-induced TNF secretion [16,17] and may therefore protect against clinical disease [3,18], but IgM reactivities also correlate with the severity of disease [10]. The potential role of these IgM antibodies in protecting against disease was not demonstrated in this study.…”

Section: Discussionmentioning

confidence: 80%

Soluble products of inflammatory reactions are not induced in children with asymptomatic Plasmodium falciparum infections

Jakobsen

Mckay

Njie

et al. 1996

Clinical and Experimental Immunology

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SUMMARYA proportion of children with Plasmodium falciparum infection have a high parasitaemia without accompanying fever, indicative of different clinical thresholds of parasitaemia. Higher levels of IL-10, IL-1Ra and sIL-4R but not sIL-2R were found in children with P. falciparum malaria, compared with levels in children with asymptomatic P. falciparum infections and in healthy children. Concentrations of IL-10 and IL-1Ra were correlated with levels of parasitaemia, but the association of cytokine levels with disease was independent of the association with parasitaemia. Children may tolerate a high parasitaemia by neutralizing the parasite-derived toxins. When studying potential antitoxic molecules we found that children with symptomatic infections had lower concentrations of a phospholipid-binding molecule,¯2-glycoprotein I (¯2-GPI), compared with children with asymptomatic infections or healthy children. In conclusion, cytokines were found in much higher concentrations in children with symptomatic P. falciparum malaria than in children with asymptomatic infections, whilst the former had lower concentrations of¯2-GPI.

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Section: Discussionmentioning

confidence: 80%

Soluble products of inflammatory reactions are not induced in children with asymptomatic Plasmodium falciparum infections

Jakobsen

Mckay

Njie

et al. 1996

Clinical and Experimental Immunology

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“…[3] have discussed the role of "anii-parasiie" lersus "anti-disease" vaccine in relation to malaria. They have cited evidence lo show that soluble antigens (toxins) released from Plasnwdium falcipiirum have properties of baeterial lipopolysaccharides and induce over-produclion of TNF which is responsible for the disease.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore. Ihey have proposed ihc possibility of an "anli-toxic vaccine' thai prevents the serious pathological complications of the disease [3]. CF is a unique cytokine induced by DV which is responsible for the production of most of the pathological lesions which could be prevented by passive immunization [16.17,20].…”

Section: Discussionmentioning

confidence: 99%

Active immunization by a dengue virus-induced cytokine

Chaturvedi¹,

Mukerjee²,

Dhawan³

1994

Clinical and Experimental Immunology

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SUMMARYDengue type 2 virus (DV)-induccd cytotoxic factor (CF) is capable of reproducing various palhological lesions in mice that are seen in human dengue. The present study was undertaken to investigate the protective effect of active immunization of mice with CF, Mice were immunized with 5 //gof CFand prevention ofCF-induced increase in capillary permeability and damage to the bloodbrain barrier were studied at weekly intervals, up to 48 weeks, by challenging with } /(g of CF, Maximum protection against increase in capillary permeability and damage to the blood-brain barrier was observed in week 4 after immunization. A breakthrough in the protection occurred with higher doses of CF in a dose-dependent manner. Challenge with a lethal intraccrcbrat (i.e.) dose of DV showed significantly prolonged mean survival time and delayed onset ofsymptoms of sickness in the immunized mice compared with the normal mice, but the titre ofthe virus in the brain was similar in the two groups. On i,p. challenge with the virus the protection against damage to the blood-brain barrier was 86 + 7",' ;i at week 4 and 17 + 4% at week 26 after immunization. Sera obtained from the immunized mice showed the presenee of CF-sp>eeific antibodies by ELISA, Western blot, and by neutralization of the cytotoxic activity of CF in vitro. The present study describes successful prevention ofa cytokine-induced pathology by speeific aetive immunization.

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“…Further characterization of the molecule(s) involved and elucidation of their mechanism of action are required to increase our understanding of the complications of malaria, and for the development of anti-disease vaccines and therapy [32], and possibly also for defining novel substances to decrease insulin resistance in Type I1 diabetes and other clinical situations.…”

Section: Discussionmentioning

confidence: 99%

Malarial toxic antigens synergistically enhance insulin signalling

et al. 1992

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Hypoglycaemia is a major complication of severe malaria [(1990) Trans. Roy. Sot. Trop. Med. 84 (suppl. 2) l-651, especially cerebral malaria, in which it is associated with increased mortality [( ) Lancet 336. 1039[( -1043 ]. Here we report that TMAs can act synergistically with insulin in both stimulating lipogenesis and inhibiting lipolysis in rat adipocytes in vitro, and, furthermore.that they act synergistically with insulin in the induction of hypoglycaemia in vivo.

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The malaria vaccine: anti-parasite or anti-disease?

Cited by 152 publications

References 19 publications

Soluble products of inflammatory reactions are not induced in children with asymptomatic Plasmodium falciparum infections

Soluble products of inflammatory reactions are not induced in children with asymptomatic Plasmodium falciparum infections

Active immunization by a dengue virus-induced cytokine

Malarial toxic antigens synergistically enhance insulin signalling

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