Current Status of Malaria Vaccine Development

Chauhan, Virander S.; Bhardwaj, D. K.

doi:10.1007/3-540-36488-9_5

Cited by 8 publications

(7 citation statements)

References 238 publications

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“…The discovery of rodent plasmodia by Vincke and Yoeli (Killick-Kendrick and Peters 1978) resulted in the replacement of the avian by the rodent model for practical reasons, using P. berghei (Vincke and Lips 1948), P. chabaudi (Landau 1965) or P. yoelii (Landau and Killick-Kendrick 1966) as parasite species. However, as still no satisfactory primate model for human P. falciparum malaria has been found yet (Chauhan and Bhardwaj 2003), the question is whether the phylogenetic relationships between the hosts or the parasites are more important for experimental malaria research, and thus, whether an avian or a rodent in vivo model is to be preferred.…”

Section: Discussionmentioning

confidence: 98%

Bayesian analysis of new and old malaria parasite DNA sequence data demonstrates the need for more phylogenetic signal to clarify the descent of Plasmodium falciparum

et al. 2007

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Molecular systematic studies published during the last 15 years to clarify the phylogenetic relationships among the malaria parasites have led to two major hypotheses on the descent of Plasmodium falciparum: One supports an avian origin as a result of a relatively recent host switch, and another one favours the evolutionary development of P. falciparum together with its human host from primate ancestors. In this paper, we present phylogenetic analyses of three different Plasmodium genes, the nuclear 18 small sub-unit (SSU) ribosomal ribonucleic acid (rRNA), the mitochondrial cytochrome b (cyt b) and the plastid caseinolytic protease C (ClpC) gene, using numerous haemosporidian parasite DNA sequences obtained from the GenBank as well as several new sequences for major malaria parasites including the avian one Plasmodium cathemerium, which has never been considered in molecular phylogenetic analyses before. Most modern and sophisticated DNA substitution models based on Bayesian inference analysis were applied to estimate the cyt b and ClpC phylogenetic trees, whereas the 18 SSU rRNA gene was examined with regards to its secondary structure using PHASE software. Our results indicate that the data presently available are generally neither sufficient in number nor in information to solve the problem of the phylogenetic origin of P. falciparum.

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Section: Discussionmentioning

confidence: 98%

Bayesian analysis of new and old malaria parasite DNA sequence data demonstrates the need for more phylogenetic signal to clarify the descent of Plasmodium falciparum

et al. 2007

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“…This vaccine showed great promise in early studies (59), but the results were not reproduced in different settings or when conducted by different investigators (60,61). A number of other studies using recombinant antigens have either failed to proceed or are moving forward slowly, despite oftentimes extremely encouraging data in animal model systems (62)(63)(64)(65)(66)(67)(68)(69). It is clear that the challenges to developing a malaria vaccine are very significant, given that there is no vaccine 21 years after blood-stage antigens were first cloned, and most optimistic predictions would say a vaccine is still at least 10 years away.…”

Section: Vaccine Approaches and Immunological Challengesmentioning

confidence: 99%

The immunological challenge to developing a vaccine to the blood stages of malaria parasites

Good

Stanisic

et al. 2004

Immunological Reviews

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Twenty-one years after malaria antigens were first cloned, a vaccine still appears to be a long way off. There have been periods of great excitement, and in model systems, subunit vaccine homologs can induce robust protection. However, significant challenges exist concerning antigenic variation and polymorphism, immunological non-responsiveness to individual vaccine antigens, parasite-induced apoptosis of immune effector and memory cells, and immune deviation as a result of maternal immunity and alterations of dendritic cell function. Novel approaches will be required. This review addresses some of the approaches that might present malaria antigens in a way designed to induce superior immune responses or that target novel conserved epitopes. Cell-mediated immunity, acting independently of antibody, may exert potent anti-parasite effects, and identification of multiple target antigens/epitopes could lead to the development of vaccines with profound efficacy.

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“…In different model systems (animal models and in vitro human systems), these immune responses have been shown to be capable of killing parasites (4). These observations have provided the foundations for vaccine strategies aimed at sporozoites, liver stage forms, blood stage forms, and sexual forms (5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 95%

DEVELOPMENT AND REGULATION OF CELL-MEDIATED IMMUNE RESPONSES TO THE BLOOD STAGES OF MALARIA: Implications for Vaccine Research

Good

Wykes³

et al. 2005

Annu. Rev. Immunol.

171

133

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The immune response to the malaria parasite is complex and poorly understood. Although antibodies and T cells can control parasite growth in model systems, natural immunity to malaria in regions of high endemicity takes several years to develop. Variation and polymorphism of antibody target antigens are known to impede immune responses, but these factors alone cannot account for the slow acquisition of immunity. In human and animal model systems, cell-mediated responses can control parasite growth effectively, but such responses are regulated by parasite load via direct effects on dendritic cells and possibly on T and B cells as well. Furthermore, high parasite load is associated with pathology, and cell-mediated responses may also harm the host. Inflammatory cytokines have been implicated in the pathogenesis of cerebral malaria, anemia, weight loss, and respiratory distress in malaria. Immunity without pathology requires rapid parasite clearance, effective regulation of the inflammatory anti-parasite effects of cellular responses, and the eventual development of a repertoire of antibodies effective against multiple strains. Data suggest that this may be hastened by exposure to malaria antigens in low dose, leading to augmented cellular immunity and rapid parasite clearance.

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Current Status of Malaria Vaccine Development

Cited by 8 publications

References 238 publications

Bayesian analysis of new and old malaria parasite DNA sequence data demonstrates the need for more phylogenetic signal to clarify the descent of Plasmodium falciparum

Bayesian analysis of new and old malaria parasite DNA sequence data demonstrates the need for more phylogenetic signal to clarify the descent of Plasmodium falciparum

The immunological challenge to developing a vaccine to the blood stages of malaria parasites

DEVELOPMENT AND REGULATION OF CELL-MEDIATED IMMUNE RESPONSES TO THE BLOOD STAGES OF MALARIA: Implications for Vaccine Research

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