Malaria Vaccine: Candidate Antigens, Mechanisms, Constraints and Prospects

Carvalho, Leonardo J. M.; Daniel-Ribeiro, Cláudio Tadeu; Goto, Hiro

doi:10.1046/j.1365-3083.2002.01160.x

Cited by 64 publications

(55 citation statements)

References 124 publications

(147 reference statements)

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“…Other mechanisms implicated in protection are cytotoxicity by activated cytotoxic T lymphocytes through the release of perforin and granzyme B and the induction of apoptosis by the cross-linking of Fas molecules expressed on the infected hepatocytes (8,44). These findings emphasize the importance of developing preerythrocytic malaria vaccines and vaccination strategies that are able to induce not only antibody response but also a strong T-cell immunity.…”

Section: Discussionmentioning

confidence: 95%

“…While antibodies have been correlated with protection from infection with the malaria parasite (25,27), T cells are believed to play a critical role in the elimination of liver-stage parasites and protection against the disease (29,36). Studies with mice indicate that a major mechanism of protection against liver-stage malaria is the production of IFN-␥ by activated CD8 ϩ T cells, which induces infected hepatocytes to synthesize nitric oxide, a molecule with a potent antiparasitic activity (8,13,50,51).…”

Section: Discussionmentioning

confidence: 99%

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Impact of Recombinant Adenovirus Serotype 35 Priming versus Boosting of aPlasmodium falciparumProtein: Characterization of T- and B-Cell Responses to Liver-Stage Antigen 1

et al. 2008

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Prime-boost vaccination regimens with heterologous antigen delivery systems have indicated that redirection of the immune response is feasible. We showed earlier that T-cell responses to circumsporozoite (CS) protein improved significantly when the protein is primed with recombinant adenovirus serotype 35 coding for CS (rAd35.CS). The current study was designed to answer the question whether such an effect can be extended to liver-stage antigens (

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Impact of Recombinant Adenovirus Serotype 35 Priming versus Boosting of aPlasmodium falciparumProtein: Characterization of T- and B-Cell Responses to Liver-Stage Antigen 1

et al. 2008

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“…Development of an effective malaria vaccine has been so far a disappointing enterprise, and one of the main reasons for the failure is the limited knowledge on the mechanisms of immunity (Carvalho et al 2002). Therefore, understanding the implications of thymus atrophy and thymocyte depletion on the acquisition of immunity to malaria is an important issue.…”

Section: Discussionmentioning

confidence: 99%

Plasmodium berghei ANKA infection induces thymocyte apoptosis and thymocyte depletion in CBA mice

Carvalho

Ferreira-da-Cruz

Daniel-Ribeiro

et al. 2006

Mem. Inst. Oswaldo Cruz

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Immune responses to malaria infections are characterized by strong T and B cell activation, which, in Key words: malaria -thymus -Plasmodium berghei -mice Malaria infections are characterized by defective immune responses, with poor efficacy and, in some cases, with the occurrence of immunopathology. The major lifethreatening malaria-related complications -cerebral malaria and severe anemia -have a strong immunological component in humans (Mackintosh et al. 2004) as well as in experimental models (De Souza & Riley 2002, Carvalho et al. 2003.The Plasmodium berghei ANKA infection in CBA mouse is an established model of malaria with neurological involvement (the so-called experimental cerebral malaria), and infection with blood stage parasites leads to 100% lethality. The immune response in this model is not only ineffective against parasite growth but also responsible for the 60-90% incidence of cerebral malaria (CM), mainly characterized by strong Th1 T cell responses (Hunt & Grau 2003), macrophage hyperactivation (Carvalho et al. 2000) and also CD8 + T cell cytotoxicity (Belnoue et al. 2002). T lymphocytes are central in CM pathogenesis. Early thymectomized CBA mice become resistant to CM development (Grau et al. 1986). Treatment of adult mice with anti-CD4 or anti-CD8 monoclonal antibodies also abrogate CM development, depending on the moment they are administered -early in infection for anti-CD4 and late in the infection for anti-CD8 (Grau et al. 1986 al. 2002). CM seems to be mediated by cells bearing αβ T cell receptors (TCR), since mice lacking T cells of the αβ lineage (TCR αβ -/-), but not of the γδ lineage (TCR γδ -/-), were resistant to CM development (Boubou et al. 1999). In addition, these authors showed that expression of CM was associated with an increase in T cells bearing the Vβ8.1 and Vβ8.2 segments, and CM expression was reduced in mice rendered deficient in cells bearing these segments.Although all the events concerning the participation of T cells in CM physiopathogenesis are related to peripheral responses, events occurring in the thymus cannot be disregarded. Indeed, infection by other protozoan parasites can potentially affect thymic function and then modulate T cell responses. In Trypanosoma cruzi infection in Balb/c mouse, intense thymic atrophy is reported, with loss of double positive immature thymocytes and appearance of such immature cells in secondary lymphoid organs (Mendes-da-Cruz et al. 2003). In addition, lymphocytes carrying normally forbidden TCR Vβ families are also exported from the thymus. According to these authors such cells could play a role in the autoimmune responses commonly observed during T. cruzi infections. Therefore, infection can affect thymic function resulting in pathological consequences or altering the efficacy of the immune response. In malaria, the consequences of malaria infection on thymus structure and function have been overlooked, with few works on the subject (Krettli & Nussenzweig 1974). In the present work, we evaluated the sequential histologica...

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“…As yet, no protective vaccine against the pathogenic blood stages of malaria exists, although trials in humans with candidate antigens encourage the view that such a vaccine is achievable (1). Most recently, a malaria vaccine based on a sporozoite and preerythrocytic stage antigen, the circumsporozoite protein, has shown convincing efficacy in a field trial (2).…”

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confidence: 99%

A genetic approach to thede novoidentification of targets of strain-specific immunity in malaria parasites

Martinelli

Cheesman

Hunt

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Vaccine research in malaria has a high priority. However, identification of specific antigens as candidates for vaccines against asexual blood stages of malaria parasites has been based on largely circumstantial evidence. We describe here how genes encoding target antigens of strain-specific immunity in malaria can be directly located in the parasite's genome without prior information concerning their identity, by the method we call linkage group selection. Two genetically distinct clones of the rodent malaria parasite Plasmodium chabaudi chabaudi, each of which induces an immunity in laboratory mice that is more protective against challenge with itself than with the heterologous strain, were genetically crossed, and the uncloned cross progeny selected in mice that had been made partially immune by infection and drug cure with one or the other parental strain. Proportions of parental alleles in the selected and unselected cross progeny were compared by using quantitative genome-wide molecular markers. A small number, including groups of linked markers forming socalled selection valleys, were markedly reduced under strainspecific immune pressure. A very prominent selection valley was found to contain the gene for merozoite surface protein-1, a major candidate antigen for malaria vaccine development, at the locus at which the strongest reduction under strain-specific immune selection was detected. Closely linked to the merozoite surface protein-1 gene was a gene containing the signature motif of the ring-infected erythrocyte surface antigen family. Another affected locus, unlinked to this selection valley, contained a member of the serine repeat antigen gene family.amplified fragment length polymorphism ͉ merozoite surface protein

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Malaria Vaccine: Candidate Antigens, Mechanisms, Constraints and Prospects

Cited by 64 publications

References 124 publications

Impact of Recombinant Adenovirus Serotype 35 Priming versus Boosting of aPlasmodium falciparumProtein: Characterization of T- and B-Cell Responses to Liver-Stage Antigen 1

Impact of Recombinant Adenovirus Serotype 35 Priming versus Boosting of aPlasmodium falciparumProtein: Characterization of T- and B-Cell Responses to Liver-Stage Antigen 1

Plasmodium berghei ANKA infection induces thymocyte apoptosis and thymocyte depletion in CBA mice

A genetic approach to thede novoidentification of targets of strain-specific immunity in malaria parasites

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