Vaccination against malaria: targets, strategies and potentiation of immunity to blood stage parasites

Taylor‐Robinson, Andrew W.

doi:10.2741/robinson

Cited by 9 publications

(7 citation statements)

References 105 publications

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“…The immunological paradigm separating CD4 + T helper (Th) cells has helped in the molecular characterization of antimalarial immune response. 7 Briefly, Th1 cells produce IL-2, IFN-γ, IL-12, and TNF, and mediate macrophage activation, whereas Th2 cells secrete IL-4, IL-6, and IL-10, and help in antibody production. The nature of CD4 + T cell response in mice and humans is apparently similar, if not identical.…”

Section: Immunity To Malariamentioning

confidence: 99%

The dichotomy (generation of MAbs with functional heterogeneity) in antimalarial immune response in vaccinated/protected mice

Singh

Prakash²

2014

Human Vaccines & Immunotherapeutics

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Globally, vaccines have emerged as one of the most effective, safe, and cost-effective public health interventions, and are known to save 2-3 million lives, annually. However, despite various commendable efforts, a suitable human malaria vaccine is yet to see the light of the day. The lack of our complete understanding of the molecular mechanisms of pathogenesis and immune protection in malaria appears to be responsible for this state. Earlier, our laboratory has reported that Swiss mice vaccinated with Plasmodium yoelii nigeriensis-total parasite antigens soluble in culture medium and saponin, following a 100% lethal challenge, showed 60% protection. The monoclonal antibodies (MAbs) generated from the splenocytes of these vaccinated/protected mice, following characterization by in vitro merozoite invasion inhibition assay, ex vivo macrophage phagocytosis assay, and in vivo passive transfer of protection test, belonged to 2 distinct groups-a larger group of MAbs inhibited<58% Mz invasion and transferred 30% passive protection, whereas a smaller group of MAbs inhibited 86% Mz invasion and transferred 60% passive protection. Additionally, the MAbs of the smaller group, as compared with the larger one, mediated nearly 2.4-fold enhanced macrophage phagocytosis of infected-erythrocytes, in vitro. These results thus clearly showed a dichotomy among the generated MAbs. An exploration of the phenomenon of dichotomy in protective immunity in malaria by using various hosts and malaria parasite combinations, especially at the level of antibodies, cells, and cytokines, may add new insights to our understanding of the protective immunity, and help in the identification of biomarkers/biosignatures of immune protection and development of future human malaria vaccines.

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Section: Immunity To Malariamentioning

confidence: 99%

The dichotomy (generation of MAbs with functional heterogeneity) in antimalarial immune response in vaccinated/protected mice

Singh

Prakash²

2014

Human Vaccines & Immunotherapeutics

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“…Se han diseñado vacunas contra P falciparum y P vivax destinadas a: a) prevenir la infección al humano y van dirigidas contra los esporozoitos y las etapas hepáticas; b) encaminadas a detener la propagación del parásito en la sangre del huésped y van enfocadas contra las etapas asexuales intraeritrocíticas; c) destinadas a reducir o interrumpir la transmisión del parásito del huésped humano al mosquito y van dirigidas contra las etapas sexuales del parásito (gametocitos, gametos, zigoto y etapas esporogónicas en el vector), y se conocen como vacunas para el bloqueo de la transmisión (VBT) 49, y d) las vacunas anti-enfermedad, también conocidas como antitóxicas, destinadas a disminuir o inhibir algunas de las manifestaciones clínicas de la enfermedad, como la fiebre, que se originan como consecuencia de la respuesta inflamatoria del huésped (mediada por citocinas como el TNFα e Interleucinas IL-1, IL-4, IL-6) en contra de los exoantígenos y moléculas tóxicas derivadas del metabolismo del parásito. 11,14,[49][50][51] La estrategia actual de las VBT consiste en la inducción de una respuesta humoral en el huésped vertebrado, mediante anticuerpos dirigidos contra antígenos de las proteínas de superficie de los gametocitos o gametos. Estos anticuerpos estarían actuando en el intestino del mosquito de 5 a 10 minutos después de la ingestión de sangre, previniendo con esto la fertilización, inhibiendo el reconocimiento celular entre gametos o bien, destruyendo los gametos o los zigotos recién fertilizados, mediante reacciones mediadas por complemento.…”

Section: Respuesta Celularunclassified

Gametocitos de Plasmodium vivax y Plasmodium falciparum: etapas relegadas en el desarrollo de vacunas

Contreras-Ochoa¹,

Ramsey²

2004

Salud pública Méx

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Plasmodium gametocytes are responsible for transmission from the vertebrate host to the mosquito. Plasmodium gametocytes undergo a complex cycle from asexual stages, through a poorly understood process characterized by expression of stage-specific proteins and adhesion molecules. Gametocytes are capable of inducing specific humoral IgG, and cellular responses, which include induction of TNFalpha, IFNgamma and gammadelta+ lymphocyte proliferation, in addition to immune responses to other stages of the parasite (sporozoite, exo-erythrocytic stages, erythrocytic stages). Although transmission-blocking vaccines against Plasmodium do not currently include components against the gametocytes (rather they focus on gametes, zygotes or ookinetes, stages which occur in the mosquito), further understanding of the mechanisms underlying gametocytogenesis and immune responses against these stages may provide additional strategies for more effective transmission inhibition.

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“…However, the prospects for malaria, after two decades of molecular biological based research, are looking brighter (Good and Doolan 1999;Taylor-Robinson 2000). A central problem in vaccine development in general has been difficulty in generating high levels of antigen-specific T cells, particularly CD8 + T lymphocytes, by immunization with purified antigens.…”

Section: Introductionmentioning

confidence: 98%

“…Furthermore, protein subunit vaccines in combination with a variety of adjuvants, such as alum or mineral oils, generally stimulate very high titre antibody responses, which will neutralise extracellular pathogens but have little effect on intracellular pathogens (Bowersock and Martin 1999;Makela 2000). Many pathogens, notably apicomplexans, are intracellular for large periods in their mammalian host and the key effectors against these are often CD8 + T cells (McKeever et al 1994;Abrahamsen 1998;Khan et al 1999;Preston et al 1999;Doolan and Hoffman 2000;Taylor-Robinson 2000).…”

Section: Introductionmentioning

confidence: 99%

Prime-boost: the way forward for recombinant vaccines against apicomplexan parasites. A Theileria perspective

2002

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A good CD8 + response is required for immunity to many intracellular pathogens. Traditional antigen delivery using isolated sub-units or killed pathogens and adjuvant stimulates strong antibody responses but weak T-cell reactivity. Attenuated vaccines are usually more effective. The prime-boost delivery system based on immunisation with a naked DNA antigen-gene construct followed by boosting with an attenuated vaccinia virus expressing the same antigen is proving to be a powerful way to stimulate antigenspecific CD8 responses. Success using single epitopes is possible in malaria and we believe this approach holds much promise for other apicomplexan parasites such as Theileria spp.

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Vaccination against malaria: targets, strategies and potentiation of immunity to blood stage parasites

Cited by 9 publications

References 105 publications

The dichotomy (generation of MAbs with functional heterogeneity) in antimalarial immune response in vaccinated/protected mice

The dichotomy (generation of MAbs with functional heterogeneity) in antimalarial immune response in vaccinated/protected mice

Gametocitos de Plasmodium vivax y Plasmodium falciparum: etapas relegadas en el desarrollo de vacunas

Prime-boost: the way forward for recombinant vaccines against apicomplexan parasites. A Theileria perspective

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