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

López, Carolina; Yepes-Pérez, Yoelis; Hincapié-Escobar, Natalia; Díaz-Arévalo, Diana; Patarroyo, Manuel A.

doi:10.3389/fimmu.2017.00126

Cited by 42 publications

(33 citation statements)

References 249 publications

(288 reference statements)

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“…Plasmodium vivax has previously been considered benign; however, during the last few years, P. vivax is estimated to have been responsible for 3100 deaths [ 1 ]. Due to some specific characteristics that make it distinct from P. falciparum, such as the fact that the P. vivax hypnozoite can become reactivated, cause repeated clinical malaria attacks, and undergo onward transmission, emerging data indicate that P. vivax is very often associated with severe symptoms [ 2 , 3 ]. Developing a vaccine is considered to be one of several strategies to control and eradicate vivax malaria.…”

Section: Introductionmentioning

confidence: 99%

“…The glycosylphosphatidylinositol-anchored proteins (GPI-APs) are one type of protein antigen important for parasite invasion [ 10 ]. Several GPI-APs have been discovered and characterized as blood-stage vaccine candidates against P. vivax infection; these include PvMSP-1, PvMSP-3, PvMSP-4, PvMSP-8, PvMSP-9, PvMSP-10, Pv12, Pv34, Pv38 and PvMSP1P [ 3 , 11 ]. A new erythrocyte-binding protein named GPI-anchored micronemal antigen (GAMA) was first identified in P. falciparum [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Immunogenicity of glycosylphosphatidylinositol-anchored micronemal antigen in natural Plasmodium vivax exposure

Changrob

Han

et al. 2017

Malar J

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Background Plasmodium vivax is the most geographically widespread malaria species and codominates with Plasmodium falciparum, the deadliest form of the malaria parasite. For the last few years, the number of vivax malaria cases has increased, but vivax malaria is still considered a neglected disease. During the blood stages of their life cycle, P. vivax parasites export several hundred proteins into host red blood cells. Some of these exported proteins have been discovered and studied for use as a blood-stage malaria vaccine. The P. vivax glycosylphosphatidylinositol (GPI)-anchored micronemal antigen (PvGAMA) was identified in previous study, which plays an important role in parasite invasion. To support the hypothesis that PvGAMA can induce an immune response in natural exposure, the antibody responses and cellular immunity against this antigen was demonstrated during and post-infection.MethodsThe recombinant protein PvGAMA was expressed and purified by wheat germ cell-free (WGCF) system. The analysis of humoral and cellular immune responses to the PvGAMA antigen during infection and post-infection with the P. vivax parasite were done by enzyme-linked immunosorbent assay (ELISA) techniques.ResultsDuring P. vivax infection, 95% of patients showed significant antibody responses to PvGAMA antigen. The cytophilic IgG1 and IgG3 isotypes were the major isotypes produced in response to PvGAMA. A cross-sectional study of anti-PvGAMA responses during and post-infection with P. vivax found that the majority of individuals, approximately 54% of patients, were shown to maintain a positive anti-PvGAMA titre at 3 months post-infection, and some patients had the ability to maintain an antibody response for up to 12 months post-infection. Moreover, PvGAMA had the ability to stimulate a cellular immune response that was characterized by the production of the cytokines IL-2, IFN-γ and IL-10. The levels of the cytokines IFN-γ and IL-10 were significantly increased in PvGAMA-stimulated lymphocyte cultures.ConclusionsTaken together, PvGAMA had potential to induce an immune response both humoral and cellular immunity in naturally acquired P. vivax infection individuals during infection and post-infection. Therefore, PvGAMA could be as a vaccine candidate to stimulate immune response against P. vivax infection.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunogenicity of glycosylphosphatidylinositol-anchored micronemal antigen in natural Plasmodium vivax exposure

Changrob

Han

et al. 2017

Malar J

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“…Developing countries desperately need strategies aimed at preventing malaria (especially that caused by P. vivax ), such as approaches for developing specific drugs and protective vaccines which are currently unavailable. Although there are P. vivax vaccines in phases I and IIa (López et al, 2017 ), they have not induced sterile protection (Bennett et al, 2016 ). Developing a P. vivax vaccine requires studies analyzing naturally-infected patients' immune response regarding proteins involved in erythrocyte invasion.…”

Section: Discussionmentioning

confidence: 99%

The in Vitro Antigenicity of Plasmodium vivax Rhoptry Neck Protein 2 (PvRON2) B- and T-Epitopes Selected by HLA-DRB1 Binding Profile

López

Yepes-Pérez

Díaz-Arévalo

et al. 2018

Front. Cell. Infect. Microbiol.

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Malaria caused by Plasmodium vivax is a neglected disease which is responsible for the highest morbidity in both Americas and Asia. Despite continuous public health efforts to prevent malarial infection, an effective antimalarial vaccine is still urgently needed. P. vivax vaccine development involves analyzing naturally-infected patients' immune response to the specific proteins involved in red blood cell invasion. The P. vivax rhoptry neck protein 2 (PvRON2) is a highly conserved protein which is expressed in late schizont rhoptries; it interacts directly with AMA-1 and might be involved in moving-junction formation. Bioinformatics approaches were used here to select B- and T-cell epitopes. Eleven high-affinity binding peptides were selected using the NetMHCIIpan-3.0 in silico prediction tool; their in vitro binding to HLA-DRB1*0401, HLA-DRB1*0701, HLA-DRB1*1101 or HLA-DRB1*1302 was experimentally assessed. Four peptides (39152 (HLA-DRB1*04 and 11), 39047 (HLA-DRB1*07), 39154 (HLADRB1*13) and universal peptide 39153) evoked a naturally-acquired T-cell immune response in P. vivax-exposed individuals from two endemic areas in Colombia. All four peptides had an SI greater than 2 in proliferation assays; however, only peptides 39154 and 39153 had significant differences compared to the control group. Peptide 39047 was able to significantly stimulate TNF and IL-10 production while 39154 stimulated TNF production. Allele-specific peptides (but not the universal one) were able to stimulate IL-6 production; however, none induced IFN-γ production. The Bepipred 1.0 tool was used for selecting four B-cell epitopes in silico regarding humoral response. Peptide 39041 was the only one recognized by P. vivax-exposed individuals' sera and had significant differences concerning IgG subclasses; an IgG2 > IgG4 profile was observed for this peptide, agreeing with a protection-inducing role against P. falciparum and P. vivax as previously described for antigens such as RESA and MSP2. The bioinformatics results and in vitro evaluation reported here highlighted two T-cell epitopes (39047 and 39154) being recognized by memory cells and a B-cell epitope (39041) identified by P. vivax-exposed individuals' sera which could be used as potential candidates when designing a subunit-based vaccine.

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“…MSP1 is the major MSP and has been implicated in many P. falciparum receptor–ligand (glycophorin A, B and 3 and heparin) and protein–protein interactions (MSP6-MSP7-RhopH3-RAPs) [ 7 , 8 , 11 ]. It has been the object of significant antigenic and immunological studies highlighting its importance as P. falciparum and P. vivax vaccine antigen candidate [ 60 , 61 ]. The other surface antigen group selected here included the Plasmodium -specific 6-Cys family containing a cysteine-rich domain, the 6-cysteine or s48/45 domain [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Self-assembling functional programmable protein array for studying protein–protein interactions in malaria parasites

Arévalo-Pinzón

González‐González

Suárez

et al. 2018

Malar J

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BackgroundPlasmodium vivax is the most widespread malarial species, causing significant morbidity worldwide. Knowledge is limited regarding the molecular mechanism of invasion due to the lack of a continuous in vitro culture system for these species. Since protein–protein and host–cell interactions play an essential role in the microorganism’s invasion and replication, elucidating protein function during invasion is critical when developing more effective control methods. Nucleic acid programmable protein array (NAPPA) has thus become a suitable technology for studying protein–protein and host–protein interactions since producing proteins through the in vitro transcription/translation (IVTT) method overcomes most of the drawbacks encountered to date, such as heterologous protein production, stability and purification.ResultsTwenty P. vivax proteins on merozoite surface or in secretory organelles were selected and successfully cloned using gateway technology. Most constructs were displayed in the array expressed in situ, using the IVTT method. The Pv12 protein was used as bait for evaluating array functionality and co-expressed with P. vivax cDNA display in the array. It was found that Pv12 interacted with Pv41 (as previously described), as well as PvMSP142kDa, PvRBP1a, PvMSP8 and PvRAP1.ConclusionsNAPPA is a high-performance technique enabling co-expression of bait and query in situ, thereby enabling interactions to be analysed rapidly and reproducibly. It offers a fresh alternative for studying protein–protein and ligand–receptor interactions regarding a parasite which is difficult to cultivate (i.e. P. vivax).Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2414-2) contains supplementary material, which is available to authorized users.

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

Cited by 42 publications

References 249 publications

Immunogenicity of glycosylphosphatidylinositol-anchored micronemal antigen in natural Plasmodium vivax exposure

Immunogenicity of glycosylphosphatidylinositol-anchored micronemal antigen in natural Plasmodium vivax exposure

The in Vitro Antigenicity of Plasmodium vivax Rhoptry Neck Protein 2 (PvRON2) B- and T-Epitopes Selected by HLA-DRB1 Binding Profile

Self-assembling functional programmable protein array for studying protein–protein interactions in malaria parasites

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