scholarly journals Efficacy of a Plasmodium vivax Malaria Vaccine Using ChAd63 and Modified Vaccinia Ankara Expressing Thrombospondin-Related Anonymous Protein as Assessed with Transgenic Plasmodium berghei Parasites

2013 ◽  
Vol 82 (3) ◽  
pp. 1277-1286 ◽  
Author(s):  
Karolis Bauza ◽  
Tomas Malinauskas ◽  
Claudia Pfander ◽  
Burcu Anar ◽  
E. Yvonne Jones ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Plasmodium Berghei ◽  
Malaria Vaccine ◽  
Protective Mechanisms ◽  
Content Type ◽  
Cell Responses ◽  
Malaria Vaccines ◽  
Modified Vaccinia Virus Ankara ◽  
Plasmodium Vivax Malaria ◽  
Antibody Titers

ABSTRACTPlasmodium vivaxis the world's most widely distributed malaria parasite and a potential cause of morbidity and mortality for approximately 2.85 billion people living mainly in Southeast Asia and Latin America. Despite this dramatic burden, very few vaccines have been assessed in humans. The clinically relevant vectors modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAd63 are promising delivery systems for malaria vaccines due to their safety profiles and proven ability to induce protective immune responses againstPlasmodium falciparumthrombospondin-related anonymous protein (TRAP) in clinical trials. Here, we describe the development of new recombinant ChAd63 and MVA vectors expressingP. vivaxTRAP (PvTRAP) and show their ability to induce high antibody titers and T cell responses in mice. In addition, we report a novel way of assessing the efficacy of new candidate vaccines againstP. vivaxusing a fully infectious transgenicPlasmodium bergheiparasite expressingP. vivaxTRAP to allow studies of vaccine efficacy and protective mechanisms in rodents. Using this model, we found that both CD8+T cells and antibodies mediated protection against malaria using virus-vectored vaccines. Our data indicate that ChAd63 and MVA expressing PvTRAP are good preerythrocytic-stage vaccine candidates with potential for future clinical application.

scholarly journals Evaluation of Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites as a Preerythrocytic P. vivax Vaccine

2017 ◽  
Vol 24 (4) ◽  
Author(s):  
Eduardo Alves ◽  
Ahmed M. Salman ◽  
Fabiana Leoratti ◽  
Cesar Lopez-Camacho ◽  
Martha Eva Viveros-Sandoval ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Protective Efficacy ◽  
Necrosis Factor Alpha ◽  
Human Malaria Parasite ◽  
Content Type ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Factor Alpha ◽  
Protein Immunization ◽  
Necrosis Factor

ABSTRACT Four different vaccine platforms, each targeting the human malaria parasite Plasmodium vivax cell-traversal protein for ookinetes and sporozoites (PvCelTOS), were generated and assessed for protective efficacy. These platforms consisted of a recombinant chimpanzee adenoviral vector 63 (ChAd63) expressing PvCelTOS (Ad), a recombinant modified vaccinia virus Ankara expressing PvCelTOS (MVA), PvCelTOS conjugated to bacteriophage Qβ virus-like particles (VLPs), and a recombinant PvCelTOS protein expressed in eukaryotic HEK293T cells (protein). Inbred BALB/c mice and outbred CD-1 mice were immunized using the following prime-boost regimens: Ad-MVA, Ad-VLPs, and Ad-protein. Protective efficacy against sporozoite challenge was assessed after immunization using a novel chimeric rodent Plasmodium berghei parasite (Pb-PvCelTOS). This chimeric parasite expresses P. vivax CelTOS in place of the endogenous P. berghei CelTOS and produces fully infectious sporozoites. A single Ad immunization in BALB/c and CD-1 mice induced anti-PvCelTOS antibodies which were boosted efficiently using MVA, VLP, or protein immunization. PvCelTOS-specific gamma interferon- and tumor necrosis factor alpha-producing CD8+ T cells were induced at high frequencies by all prime-boost regimens in BALB/c mice but not in CD-1 mice; in CD-1 mice, they were only marginally increased after boosting with MVA. Despite the induction of anti-PvCelTOS antibodies and PvCelTOS-specific CD8+ T-cell responses, only low levels of protective efficacy against challenge with Pb-PvCelTOS sporozoites were obtained using any immunization strategy. In BALB/c mice, no immunization regimens provided significant protection against a Pb-PvCelTOS chimeric sporozoite challenge. In CD-1 mice, modest protective efficacy against challenge with chimeric P. berghei sporozoites expressing either PvCelTOS or P. falciparum CelTOS was observed using the Ad-protein vaccination regimen.

scholarly journals Pharmacokinetics of Amodiaquine and Desethylamodiaquine in Pregnant and Postpartum Women with Plasmodium vivax Malaria

2011 ◽  
Vol 55 (9) ◽  
pp. 4338-4342 ◽  
Author(s):  
Marcus J. Rijken ◽  
Rose McGready ◽  
Vincent Jullien ◽  
Joel Tarning ◽  
Niklas Lindegardh ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Dosing Regimen ◽  
Noncompartmental Analysis ◽  
Time Data ◽  
Content Type ◽  
Concentration Time ◽  
Chromatography Tandem Mass Spectrometry ◽  
Pharmacokinetic Properties ◽  
Plasmodium Vivax Malaria ◽  
Liquid Chromatography Tandem Mass

ABSTRACTIn order to study the pharmacokinetic properties of amodiaquine and desethylamodiaquine during pregnancy, 24 pregnant women in the second and third trimesters of pregnancy and withPlasmodium vivaxmalaria were treated with amodiaquine (10 mg/kg of body weight/day) for 3 days. The same women were studied again at 3 months postpartum. Plasma was analyzed for amodiaquine and desethylamodiaquine by use of a liquid chromatography-tandem mass spectrometry method. Individual concentration-time data were evaluated using noncompartmental analysis. There were no clinically relevant differences in the pharmacokinetics of amodiaquine and desethylamodiaquine between pregnant (n= 24) and postpartum (n= 18) women. The results suggest that the current amodiaquine dosing regimen is adequate for the treatment ofP. vivaxinfections during pregnancy.

scholarly journals Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia

2016 ◽  
Vol 60 (8) ◽  
pp. 4610-4619 ◽  
Author(s):  
Lina Zuluaga-Idárraga ◽  
Silvia Blair ◽  
Sheila Akinyi Okoth ◽  
Venkatachalam Udhayakumar ◽  
Paula L. Marcet ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Standard Regimen ◽  
High Genetic Diversity ◽  
Content Type ◽  
Longitudinal Observational Study ◽  
High Incidence ◽  
Plasmodium Vivax Malaria ◽  
Previous Infection ◽  
First Recurrence ◽  
Infection Episode

ABSTRACTPlasmodium vivaxrecurrences help maintain malaria transmission. They are caused by recrudescence, reinfection, or relapse, which are not easily differentiated. A longitudinal observational study took place in Turbo municipality, Colombia. Participants with uncomplicatedP. vivaxinfection received supervised treatment concomitantly with 25 mg/kg chloroquine and 0.25 mg/kg/day primaquine for 14 days. Incidence of recurrence was assessed over 180 days. Samples were genotyped, and origins of recurrences were established. A total of 134 participants were enrolled between February 2012 and July 2013, and 87 were followed for 180 days, during which 29 recurrences were detected. The cumulative incidence of first recurrence was 24.1% (21/87) (95% confidence interval [CI], 14.6 to 33.7%), and 86% (18/21) of these events occurred between days 51 and 110. High genetic diversity ofP. vivaxstrains was found, and 12.5% (16/128) of the infections were polyclonal. Among detected recurrences, 93.1% (27/29) of strains were genotyped as genetically identical to the strain from the previous infection episode, and 65.5% (19/29) of infections were classified as relapses. Our results indicate that there is a high incidence ofP. vivaxmalaria recurrence after treatment in Turbo municipality, Colombia, and that a large majority of these episodes are likely relapses from the previous infection. We attribute this to the primaquine regimen currently used in Colombia, which may be insufficient to eliminate hypnozoites.

scholarly journals What Is Known about the Immune Response Induced by Plasmodium vivax Malaria Vaccine Candidates?

2017 ◽  
Vol 8 ◽  
Author(s):  
Carolina López ◽  
Yoelis Yepes-Pérez ◽  
Natalia Hincapié-Escobar ◽  
Diana Díaz-Arévalo ◽  
Manuel A. Patarroyo
Keyword(s):  
Immune Response ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Malaria Vaccine ◽  
Vaccine Candidates ◽  
Plasmodium Vivax Malaria

scholarly journals A chimeric protein-based malaria vaccine candidate induces robust T cell responses against Plasmodium vivax MSP119

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jairo Andres Fonseca ◽  
Monica Cabrera-Mora ◽  
Balwan Singh ◽  
Joseli Oliveira-Ferreira ◽  
Josué da Costa Lima-Junior ◽  
...  
Keyword(s):  
T Cell ◽  
Plasmodium Vivax ◽  
Malaria Vaccine ◽  
Vaccine Candidate ◽  
Chimeric Protein ◽  
T Cell Responses ◽  
Cell Responses ◽  
Malaria Vaccine Candidate

scholarly journals Antibodies to a Single, Conserved Epitope in Anopheles APN1 Inhibit Universal Transmission of Plasmodium falciparum and Plasmodium vivax Malaria

2013 ◽  
Vol 82 (2) ◽  
pp. 818-829 ◽  
Author(s):  
Jennifer S. Armistead ◽  
Isabelle Morlais ◽  
Derrick K. Mathias ◽  
Juliette G. Jardim ◽  
Jaimy Joy ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Content Type ◽  
Block Transmission ◽  
Antibody Recognition ◽  
Protective Epitope ◽  
Product Profile ◽  
Plasmodium Vivax Malaria ◽  
Transmission Blocking Vaccines ◽  
Conserved Epitope

ABSTRACTMalaria transmission-blocking vaccines (TBVs) represent a promising approach for the elimination and eradication of this disease. AnAPN1 is a lead TBV candidate that targets a surface antigen on the midgut of the obligate vector of thePlasmodiumparasite, theAnophelesmosquito. In this study, we demonstrated that antibodies targeting AnAPN1 block transmission ofPlasmodium falciparumandPlasmodium vivaxacross distantly related anopheline species in countries to which malaria is endemic. Using a biochemical and immunological approach, we determined that the mechanism of action for this phenomenon stems from antibody recognition of a single protective epitope on AnAPN1, which we found to be immunogenic in murine and nonhuman primate models and highly conserved among anophelines. These data indicate that AnAPN1 meets the established target product profile for TBVs and suggest a potential key role for an AnAPN1-based panmalaria TBV in the effort to eradicate malaria.

scholarly journals Tailoring a Combination Preerythrocytic Malaria Vaccine

2015 ◽  
Vol 84 (3) ◽  
pp. 622-634 ◽  
Author(s):  
Karolis Bauza ◽  
Erwan Atcheson ◽  
Tomas Malinauskas ◽  
Andrew M. Blagborough ◽  
Arturo Reyes-Sandoval
Keyword(s):  
Viral Vectors ◽  
Malaria Vaccine ◽  
Subunit Vaccines ◽  
Content Type ◽  
Adhesive Protein ◽  
Order Of Magnitude ◽  
Antibody Titers ◽  
Malaria Vaccine Candidate ◽  
Low Levels ◽  
Combined Trap

The leading malaria vaccine candidate, RTS,S, based on thePlasmodium falciparumcircumsporozoite protein (CSP), will likely be the first publicly adopted malaria vaccine. However, this and other subunit vaccines, such as virus-vectored thrombospondin-related adhesive protein (TRAP), provide only intermediate to low levels of protection. In this study, thePlasmodium bergheihomologues of antigens CSP and TRAP are combined. TRAP is delivered using adenovirus- and vaccinia virus-based vectors in a prime-boost regime. Initially, CSP is also delivered using these viral vectors; however, a reduction of anti-CSP antibodies is seen when combined with virus-vectored TRAP, and the combination is no more protective than either subunit vaccine alone. Using an adenovirus-CSP prime, protein-CSP boost regime, however, increases anti-CSP antibody titers by an order of magnitude, which is maintained when combined with virus-vectored TRAP. This combination regime using protein CSP provided 100% protection in C57BL/6 mice compared to no protection using virus-vectored TRAP alone and 40% protection using adenovirus-CSP prime and protein-CSP boost alone. This suggests that a combination of CSP and TRAP subunit vaccines could enhance protection against malaria.

scholarly journals Population Pharmacokinetic and Pharmacodynamic Modeling of Amodiaquine and Desethylamodiaquine in Women with Plasmodium vivax Malaria during and after Pregnancy

2012 ◽  
Vol 56 (11) ◽  
pp. 5764-5773 ◽  
Author(s):  
Joel Tarning ◽  
Palang Chotsiri ◽  
Vincent Jullien ◽  
Marcus J. Rijken ◽  
Martin Bergstrand ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Plasmodium Vivax ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Biologically Active ◽  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Content Type ◽  
Plasmodium Vivax Malaria

ABSTRACTAmodiaquine is effective for the treatment ofPlasmodium vivaxmalaria, but there is little information on the pharmacokinetic and pharmacodynamic properties of amodiaquine in pregnant women with malaria. This study evaluated the population pharmacokinetic and pharmacodynamic properties of amodiaquine and its biologically active metabolite, desethylamodiaquine, in pregnant women withP. vivaxinfection and again after delivery. Twenty-seven pregnant women infected withP. vivaxmalaria on the Thai-Myanmar border were treated with amodiaquine monotherapy (10 mg/kg/day) once daily for 3 days. Nineteen women, with and withoutP. vivaxinfections, returned to receive the same amodiaquine dose postpartum. Nonlinear mixed-effects modeling was used to evaluate the population pharmacokinetic and pharmacodynamic properties of amodiaquine and desethylamodiaquine. Amodiaquine plasma concentrations were described accurately by lagged first-order absorption with a two-compartment disposition model followed by a three-compartment disposition of desethylamodiaquine under the assumption of completein vivoconversion. Body weight was implemented as an allometric function on all clearance and volume parameters. Amodiaquine clearance decreased linearly with age, and absorption lag time was reduced in pregnant patients. Recurrent malaria infections in pregnant women were modeled with a time-to-event model consisting of a constant-hazard function with an inhibitory effect of desethylamodiaquine. Amodiaquine treatment reduced the risk of recurrent infections from 22.2% to 7.4% at day 35. In conclusion, pregnancy did not have a clinically relevant impact on the pharmacokinetic properties of amodiaquine or desethylamodiaquine. No dose adjustments are required in pregnancy.

scholarly journals The Subcellular Location of Ovalbumin in Plasmodium berghei Blood Stages Influences the Magnitude of T-Cell Responses

2014 ◽  
Vol 82 (11) ◽  
pp. 4654-4665 ◽  
Author(s):  
Jing-Wen Lin ◽  
Tovah N. Shaw ◽  
Takeshi Annoura ◽  
Aurélie Fougère ◽  
Pascale Bouchier ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Plasmodium Berghei ◽  
Parasitophorous Vacuole ◽  
T Cell Responses ◽  
Subcellular Location ◽  
Expression Level ◽  
Content Type ◽  
Cell Responses ◽  
And Function

ABSTRACTModel antigens are frequently introduced into pathogens to study determinants that influence T-cell responses to infections. To address whether an antigen's subcellular location influences the nature and magnitude of antigen-specific T-cell responses, we generatedPlasmodium bergheiparasites expressing the model antigen ovalbumin (OVA) either in the parasite cytoplasm or on the parasitophorous vacuole membrane (PVM). For cytosolic expression, OVA alone or conjugated to mCherry was expressed from a strong constitutive promoter (OVAhsp70orOVA::mCherryhsp70); for PVM expression, OVA was fused to HEP17/EXP1 (OVA::Hep17hep17). Unexpectedly, OVA expression inOVAhsp70parasites was very low, but when OVA was fused to mCherry (OVA::mCherryhsp70), it was highly expressed. OVA expression inOVA::Hep17hep17parasites was strong but significantly less than that inOVA::mCherryhsp70parasites. These transgenic parasites were used to examine the effects of antigen subcellular location and expression level on the development of T-cell responses during blood-stage infections. While all OVA-expressing parasites induced activation and proliferation of OVA-specific CD8+T cells (OT-I) and CD4+T cells (OT-II), the level of activation varied:OVA::Hep17hep17parasites induced significantly stronger splenic and intracerebral OT-I and OT-II responses than those ofOVA::mCherryhsp70parasites, butOVA::mCherryhsp70parasites promoted stronger OT-I and OT-II responses than those ofOVAhsp70parasites. Despite lower OVA expression levels,OVA::Hep17hep17parasites induced stronger T-cell responses than those ofOVA::mCherryhsp70parasites. These results indicate that unconjugated cytosolic OVA is not stably expressed inPlasmodiumparasites and, importantly, that its cellular location and expression level influence both the induction and magnitude of parasite-specific T-cell responses. These parasites represent useful tools for studying the development and function of antigen-specific T-cell responses during malaria infection.

Sign in / Sign up

Export Citation Format

Share Document