Polymorphisms in Plasmodium vivax Circumsporozoite Protein (CSP) Influence Parasite Burden and Cytokine Balance in a Pre-Amazon Endemic Area from Brazil

Ribeiro, Bruno de Paulo; Cassiano, Gustavo Capatti; Souza, Rodrigo Medeiros de; Cysne, Dalila Nunes; Grisotto, Marcos Augusto Grigolin; Santos, Ana Paula; Marinho, Cláudio Romero Farias; Machado, Ricardo Luiz Dantas; Nascimento, Flávia R.F.

doi:10.1371/journal.pntd.0004479

Cited by 19 publications

(23 citation statements)

References 31 publications

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“…Moreover, CSP is highly immunogenic and one of the most studied epitope of Plasmodium . Particularly in P. vivax the VK247 and VK210 variants are present woodwind and are highly conserved [ 32 ] which make the use of a chimeric protein joining these two variations extremely attractive for vaccine development.…”

Section: Resultsmentioning

confidence: 99%

Microcrystalline Tyrosine (MCT®): A Depot Adjuvant in Licensed Allergy Immunotherapy Offers New Opportunities in Malaria

et al. 2017

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Microcrystalline Tyrosine (MCT ® ) is a widely used proprietary depot excipient in specific immunotherapy for allergy. In the current study we assessed the potential of MCT to serve as an adjuvant in the development of a vaccine against malaria. To this end, we formulated the circumsporozoite protein (CSP) of P. vivax in MCT and compared the induced immune responses to CSP formulated in PBS or Alum. Both MCT and Alum strongly increased immunogenicity of CSP compared to PBS in both C57BL/6 and BALB/c mice. Challenge studies in mice using a chimeric P. bergei expressing CSP of P. vivax demonstrated clinically improved symptoms of malaria with CSP formulated in both MCT and Alum; protection was, however, more pronounced if CSP was formulated in MCT. Hence, MCT may be an attractive biodegradable adjuvant useful for the development of novel prophylactic vaccines.

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Section: Resultsmentioning

confidence: 99%

Microcrystalline Tyrosine (MCT®): A Depot Adjuvant in Licensed Allergy Immunotherapy Offers New Opportunities in Malaria

et al. 2017

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“…Understanding the Th1/Th2 response pattern is of great importance for understanding the host's defense, and these antagonistic responses allow for the homeostasis of the immune system, which is important for parasite containment [ 70 ]. In cases in which an inflammatory pattern is prevalent, the disease tends to be more severe [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Enteroparasite and vivax malaria co-infection on the Brazil-French Guiana border: Epidemiological, haematological and immunological aspects

et al. 2018

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Malaria-enteroparasitic co-infections are known for their endemicity. Although they are prevalent, little is known about their epidemiology and effect on the immune response. This study evaluated the effect of enteroparasite co-infections with malaria caused by Plasmodium vivax in a border area between Brazil and French Guiana. The cross sectional study took place in Oiapoque, a municipality of Amapá, on the Amazon border. Malaria was diagnosed using thick blood smears, haemoglobin dosage by an automated method and coproparasitology by the Hoffman and Faust methods. The anti-PvMSP-119 IgG antibodies in the plasma were evaluated using ELISA and Th1 (IFN-γ, TNF-α and IL-2), and Th2 (IL-4, IL-5 and IL-10) cytokine counts were performed by flow cytometry. The participants were grouped into those that were monoinfected with vivax malaria (M), vivax malaria-enteroparasite co-infected (CI), monoinfected with enteroparasite (E) and endemic controls (EC), who were negative for both diseases. 441 individuals were included and grouped according to their infection status: [M 6.9% (30/441)], [Cl 26.5% (117/441)], [E 32.4% (143/441)] and [EC 34.2% (151/441)]. Males prevailed among the (M) 77% (23/30) and (CI) 60% (70/117) groups. There was a difference in haemoglobin levels among the different groups under study for [EC-E], [EC-Cl], [E-M] and [Cl-M], with (p < 0.01). Anaemia was expressed as a percentage between individuals [CI-EC (p < 0.05)]. In terms of parasitaemia, there were differences for the groups [CI-M (p < 0.05)]. Anti-PvMSP-119 antibodies were detected in 51.2% (226/441) of the population. The level of cytokines evaluation revealed a large variation in TNF-α and IL-10 concentrations in the co-infected group. In this study we did not observe any influence of coinfection on the acquisition of IgG antibodies against PvMSP119, as well as on the profile of the cytokines that characterize the Th1 and Th2 patterns. However, co-infection increased TNF-α and IL-10 levels.

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“…The P. vivax CSP protein contains a variable central region that is composed of two nanopeptides that repeat in tandem and result in the two major molecular variants of the protein, VK210 and VK247 [ 18 ]. Local and global variations have been reported in the distribution of the two variants [ 19 , 20 ] and also variation in vector susceptibility towards the two forms [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Semi-high-throughput detection of Plasmodium falciparum and Plasmodium vivax oocysts in mosquitoes using bead-beating followed by circumsporozoite ELISA and quantitative PCR

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Tadesse

Andolina

et al. 2017

Malar J

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BackgroundThe malaria infection status of mosquitoes is commonly determined by microscopic detection of oocysts on the dissected mosquito midgut. This method is labour-intensive, does not allow processing of large numbers of mosquitoes and can be challenging in terms of objective classification of oocysts. Here, a semi-high-throughput bead-beating ELISA method is proposed for detection of the circumsporozoite protein (CSP) followed by confirmation by quantitative PCR (qPCR).MethodsCultured Plasmodium falciparum gametocytes were offered to Anopheles stephensi mosquitoes and examined by microscopy. After bead-beating, mosquito homogenate was examined by CSP-ELISA and 18S qPCR. As negative controls, mosquitoes that were offered a heat-inactivated gametocyte blood meal were used. The CSP-ELISA/qPCR methodology was applied to high and low-intensity infections of cultured P. falciparum gametocytes. A similar methodology optimized for P. vivax was used on mosquitoes that were offered blood from Ethiopian donors who were naturally infected with P. vivax.ResultsThere was considerable variation in CSP-ELISA signal and qPCR values in mosquitoes with low oocyst intensities. There was a strong agreement mosquito positivity by CSP-ELISA and by qPCR in mosquitoes that fed on cultured P. falciparum material (agreement 96.9%; kappa = 0.97) and naturally infected P. vivax parasite carriers [agreement 92.4% (kappa = 0.83)].ConclusionsThe proposed bead-beating CSP-ELISA/qPCR methodology considerably increases throughput for the detection of mosquito infection. qPCR remains necessary to confirm infections in mosquitoes with low CSP-ELISA signal. This methodology may prove particularly useful for studies where very low mosquito infection prevalence is expected and study sites where experience with oocyst detection is limited.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-2011-9) contains supplementary material, which is available to authorized users.

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Polymorphisms in Plasmodium vivax Circumsporozoite Protein (CSP) Influence Parasite Burden and Cytokine Balance in a Pre-Amazon Endemic Area from Brazil

Cited by 19 publications

References 31 publications

Microcrystalline Tyrosine (MCT®): A Depot Adjuvant in Licensed Allergy Immunotherapy Offers New Opportunities in Malaria

Microcrystalline Tyrosine (MCT®): A Depot Adjuvant in Licensed Allergy Immunotherapy Offers New Opportunities in Malaria

Enteroparasite and vivax malaria co-infection on the Brazil-French Guiana border: Epidemiological, haematological and immunological aspects

Semi-high-throughput detection of Plasmodium falciparum and Plasmodium vivax oocysts in mosquitoes using bead-beating followed by circumsporozoite ELISA and quantitative PCR

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