scholarly journals A chimeric Plasmodium vivax Merozoite Surface Protein Antibody Recognises and Blocks Erythrocytic P. cynomolgi Berok Merozoites In Vitro

2020 ◽  
Author(s):  
Fei-hu Shen ◽  
Jessica Jie Ying Ong ◽  
Yi-fan Sun ◽  
Yao Lei ◽  
Rui-lin Chu ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Plasmodium Vivax ◽  
Vaccine Candidate ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Surface Proteins ◽  
Vaccine Candidates ◽  
Long Term Culture

Research on erythrocytic Plasmodium vivax merozoite antigens is critical for identifying potential vaccine candidates in reducing vivax disease. However, many P. vivax studies are constrained by its inability to undergo long-term culture in vitro. Conserved across all Plasmodium spp, merozoite surface proteins are essential for invasion into erythrocytes and highly expressed on erythrocytic merozoites, thus making it an ideal vaccine candidate. In clinical trials, the P. vivax merozoite surface protein 1 (PvMSP1-19) vaccine candidate alone has shown to have limited immunogenicity in patients, hence we incorporate the highly conserved and immunogenic C-terminus of both P. vivax merozoite surface protein 8 (PvMSP8) and PvMSP1-19 to develop a multicomponent chimeric protein rPvMSP8+1 for immunization into mice. The resulted chimeric rPvMSP8+1 antibody was shown to recognize native protein MSP8 and MSP1-19 of mature P. vivax schizonts. In the immunized mice, elevated antibody response was observed in the rPvMSP8+1-immunized group as compared to that immunized with single antigen components. In addition, we examined the growth inhibition of these antibodies against P. cynomolgi (Berok strain) parasites, which is phylogenetically close to P. vivax and sustains long term culture in vitro. Similarly, the chimeric anti-rPvMSP8+1 antibodies recognises P. cynomolgi MSP8 and MSP1-19 on mature schizonts, and showed strong inhibition in vitro via growth inhibition assay. This study provides support for a new multi-antigen-based paradigm rPvMSP8+1 to explore potential chimeric vaccine candidates against P. vivax malaria using sister species, P. cynomolgi.

scholarly journals The Plasmodium vivax Merozoite Surface Protein 1 Paralog Is a Novel Erythrocyte-Binding Ligand of P. vivax

2013 ◽  
Vol 81 (5) ◽  
pp. 1585-1595 ◽  
Author(s):  
Yang Cheng ◽  
Yue Wang ◽  
Daisuke Ito ◽  
Deok-Hoon Kong ◽  
Kwon-Soo Ha ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vaccine Candidate ◽  
Structural Characteristics ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Open Reading Frames ◽  
Content Type ◽  
Merozoite Surface Protein 1 ◽  
Human Sera

ABSTRACTMerozoite surface protein 1 ofPlasmodium vivax(PvMSP1), a glycosylphosphatidylinositol-anchored protein (GPI-AP), is a malaria vaccine candidate forP. vivax. The paralog of PvMSP1, namedP. vivaxmerozoite surface protein 1 paralog (PvMSP1P; PlasmoDB PVX_099975), was recently identified and predicted as a GPI-AP. The similarities in genetic structural characteristics between PvMSP1 and PvMSP1P (e.g., size of open reading frames, two epidermal growth factor-like domains, and GPI anchor motif in the C terminus) led us to study this protein. In the present study, different regions of the PvMSP1P protein, demarcated based on the processed forms of PvMSP1, were expressed successfully as recombinant proteins [i.e., 83 (A, B, and C), 30, 38, 42, 33, and 19 fragments]. We studied the naturally acquired immune response against each fragment of recombinant PvMSP1P and the potential ability of each fragment to bind erythrocytes. The N-terminal fragment (83A) and two C-terminal fragments (33 and 19) reacted strongly with sera fromP. vivax-infected patients, with 50 to 68% sensitivity and 95 to 96% specificity, respectively. Due to colocalization of PvMSP1P with PvMSP1, we supposed that PvMSP1P plays a similar role as PvMSP1 during erythrocyte invasion. Anin vitrocytoadherence assay showed that PvMSP1P, especially the 19-kDa C-terminal region, could bind to erythrocytes. We also found that human sera from populations naturally exposed to vivax malaria and antisera obtained by immunization using the recombinant molecule PvMSP1P-19 inhibitedin vitrobinding of human erythrocytes to PvMSP1P-19. These results provide further evidence that the PvMSP1P might be an essential parasite adhesion molecule in theP. vivaxmerozoite and is a potential vaccine candidate againstP. vivax.

scholarly journals Merozoite Surface Protein 1 of Plasmodium vivax Induces a Protective Response against Plasmodium cynomolgi Challenge in Rhesus Monkeys

2005 ◽  
Vol 73 (9) ◽  
pp. 5936-5944 ◽  
Author(s):  
Sheetij Dutta ◽  
Deep C. Kaushal ◽  
Lisa A. Ware ◽  
Sunil K. Puri ◽  
Nuzhat A. Kaushal ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Protective Efficacy ◽  
High Titer ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Control Group ◽  
Merozoite Surface Protein 1 ◽  
Significant Difference ◽  
Peak Parasitemia

ABSTRACT The 42-kDa fragment of the merozoite surface protein 1 (MSP-142) is a leading candidate for the development of a vaccine to control malaria. We previously reported a method for the production of Plasmodium vivax MSP-142 (PvMSP-142) as a soluble protein (S. Dutta, L. W. Ware, A. Barbosa, C. F. Ockenhouse, and D. E. Lanar, Infect. Immun. 69:5464-5470, 2001). We report here a process to manufacture the same PvMSP-142 protein but as an insoluble inclusion body-derived protein which was then refolded in vitro. We compared the immunogenicity and protective efficacy of the soluble and refolded forms of PvMSP-142 protein by using a heterologous but closely related P. cynomolgi-rhesus monkey challenge model. As comparative controls we also expressed, purified, and immunized rhesus with the soluble and refolded forms of the P. cynomolgi MSP-142 (PcMSP-142) proteins. All proteins induced equally high-titer, cross-reacting antibodies. Upon challenge with P. cynomolgi, none of the MSP-142-vaccinated groups demonstrated sterile protection or a delay in the prepatent period. However, following an initial rise in parasitemia, all MSP-1-vaccinated animals had significantly lower parasite burdens as indicated by lower cumulative parasitemia, lower peak parasitemia, lower secondary peak parasitemia, and lower average daily parasitemia compared to the adjuvant control group (P < 0.05). Except the soluble PcMSP-142 group, monkeys in all other groups had fewer numbers of days with parasitemia of >10,000 parasites mm−3. Interestingly, there was no significant difference in the level of partial protection observed in the homologous and heterologous groups in this challenge model. The soluble and refolded forms of PcMSP-142 and PvMSP-142 proteins also appeared to have a similar partially protective effect.

The carboxy-terminus of merozoite surface protein 1: structure, specific antibodies and immunity to malaria

Parasitology ◽  
2009 ◽  
Vol 136 (12) ◽  
pp. 1445-1456 ◽  
Author(s):  
A. A. HOLDER
Keyword(s):  
Protective Immunity ◽  
First Generation ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Carboxy Terminus ◽  
Vaccine Candidates ◽  
Merozoite Surface Protein 1 ◽  
Early Results ◽  
Experimental Approaches

SUMMARYOver the last 30 years, evidence has been gathered suggesting that merozoite surface protein 1 (MSP1) is a target of protective immunity against malaria. In a variety of experimental approaches usingin vitromethodology, animal models and sero-epidemiological techniques, the importance of antibody against MSP1 has been established but we are still finding out what are the mechanisms involved. Now that clinical trials of MSP1 vaccines are underway and the early results have been disappointing, it is increasingly clear that we need to know more about the mechanisms of immunity, because a better understanding will highlight the limitations of our current assays and identify the improvements required. Understanding the structure of MSP1 will help us design and engineer better antigens that are more effective than the first generation of vaccine candidates. This review is focused on the carboxy-terminus of MSP1.

scholarly journals Purification, Characterization, and Immunogenicity of a Disulfide Cross-Linked Plasmodium vivax Vaccine Candidate Antigen, Merozoite Surface Protein 1, Expressed in Escherichia coli

2001 ◽  
Vol 69 (9) ◽  
pp. 5464-5470 ◽  
Author(s):  
Sheetij Dutta ◽  
Lisa A. Ware ◽  
Arnoldo Barbosa ◽  
Christian F. Ockenhouse ◽  
David E. Lanar
Keyword(s):  
Escherichia Coli ◽  
Plasmodium Vivax ◽  
Vaccine Candidate ◽  
Interleukin 2 ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Malarial Parasite ◽  
Merozoite Surface Protein 1 ◽  
Vaccine Candidate Antigen ◽  
Candidate Antigen

ABSTRACT The Plasmodium vivax merozoite surface protein 1 (MSP-1) 42-kDa fragment (PvMSP-1 p42) is a promising vaccine candidate antigen against the blood stage of the malarial parasite. We have developed a process for the production of this vaccine target, keeping in mind its use in human volunteers. A novel strain, Origami(DE3), of Escherichia coli with mutations in the glutathione and thioredoxin reductase genes yielded 60% more soluble PvMSP-1 p42 than the conventional E. coliBL21(DE3) strain. Recombinant PvMSP-1 p42 was purified to ≥99% purity with a rapid two-step protocol designed for easy scaling up. The final product had a low endotoxin content and was stable in its lyophilized form. PvMSP-1 p42 was found to have the predicted primary and tertiary structures and consisted of a single conformer containing one free cysteine, as predicted. The product was recognized by conformational monoclonal antibodies against P. vivax MSP-1. Immunogenicity studies of PvMSP-1 p42 were carried out with two strains of mice and the adjuvants Montanide ISA51 and Montanide ISA720. Both formulations were found to induce high levels of immunoglobulin G1 (IgG1), IgG2b, and IgG2a antibodies along with low levels of IgG3. Lymphocytes from animals in all the PvMSP-1 p42-immunized groups showed proliferative responses upon stimulation with PvMSP-1 p42; the cytokines interleukin 2 (IL-2), gamma interferon, IL-4, and IL-10 were detected in the culture supernatants. These results indicate that PvMSP-1 p42 in combination with both of the adjuvants elicited cellular and humoral responses in mice.

Plasmodium vivax merozoite surface proteins-3β and-3γ share structural similarities with P. vivax merozoite surface protein-3α and define a new gene family

2001 ◽  
Vol 115 (1) ◽  
pp. 41-53 ◽  
Author(s):  
Mary R Galinski ◽  
Paul Ingravallo ◽  
Claudia Corredor-Medina ◽  
Basima Al-Khedery ◽  
Marinette Povoa ◽  
...  
Keyword(s):  
Gene Family ◽  
Plasmodium Vivax ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Surface Proteins ◽  
New Gene

scholarly journals Antibody responses within two leading Plasmodium vivax vaccine candidate antigens in three geographically diverse malaria-endemic regions of India

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Sonal Kale ◽  
Chander P. Yadav ◽  
Pavitra N. Rao ◽  
Sneh Shalini ◽  
Alex Eapen ◽  
...  
Keyword(s):  
Antibody Response ◽  
Plasmodium Vivax ◽  
Malaria Vaccine ◽  
Vaccine Candidate ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Antibody Responses ◽  
Blood Stage ◽  
The Difference ◽  
Study Sites

Abstract Background Identifying highly immunogenic blood stage antigens which can work as target for naturally acquired antibodies in different eco-epidemiological settings is an important step for designing malaria vaccine. Blood stage proteins of Plasmodium vivax, apical membrane antigen-1 (PvAMA-1) and 19 kDa fragment of merozoite surface protein (PvMSP-119) are such promising vaccine candidate antigens. This study determined the naturally-acquired antibody response to PvAMA-1 and PvMSP-119 antigens in individuals living in three geographically diverse malaria endemic regions of India. Methods A total of 234 blood samples were collected from individuals living in three different eco-epidemiological settings, Chennai, Nadiad, and Rourkela of India. Indirect ELISA was performed to measure human IgG antibodies against recombinant PvAMA-1 and PvMSP-119 antigens. The difference in seroprevalence and factors associated with antibody responses at each site was statistically analysed. Results The overall seroprevalence was 40.6% for PvAMA-1 and 62.4% for PvMSP-119. Seroprevalence to PvAMA-1 was higher in Chennai (47%) followed by Nadiad (46.7%) and Rourkela (27.6%). For PvMSP-119, seroprevalence was higher in Chennai (80.3%) as compared to Nadiad (53.3%) and Rourkela (57.9%). Seroprevalence for both the antigens were found to be higher in Chennai where P. vivax is the dominant malaria species. In addition, heterogeneous antibody response was observed for PvAMA-1 and PvMSP-119 antigens at each of the study sites. Two factors, age and malaria positivity were significantly associated with seropositivity for both the antigens PvAMA-1 and PvMSP-119. Conclusion These data suggest that natural acquired antibody response is higher for PvMSP-119 antigen as compared to PvAMA-1 antigen in individuals living in three geographically diverse malaria endemic regions in India. PvMSP-119 appears to be highly immunogenic in Indian population and has great potential as a malaria vaccine candidate. The differences in immune response against vaccine candidate antigens in different endemic settings should be taken into account for development of asexual stage based P. vivax malaria vaccine, which in turn can enhance malaria control efforts.

New malaria vaccine candidates based on the Plasmodium vivax Merozoite Surface Protein-1 and the TLR-5 agonist Salmonella Typhimurium FliC flagellin

Vaccine ◽  
2008 ◽  
Vol 26 (48) ◽  
pp. 6132-6142 ◽  
Author(s):  
Daniel Y. Bargieri ◽  
Daniela S. Rosa ◽  
Catarina J.M. Braga ◽  
Bruna O. Carvalho ◽  
Fabio T.M. Costa ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Plasmodium Vivax ◽  
Malaria Vaccine ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Vaccine Candidates ◽  
Merozoite Surface Protein 1

scholarly journals Production and Preclinical Evaluation of Plasmodium falciparum MSP-119and MSP-311Chimeric Protein, PfMSP-Fu24

2014 ◽  
Vol 21 (6) ◽  
pp. 886-897 ◽  
Author(s):  
Puneet K. Gupta ◽  
Paushali Mukherjee ◽  
Shikha Dhawan ◽  
Alok K. Pandey ◽  
Suman Mazumdar ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Vaccine ◽  
Chimeric Protein ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Surface Proteins ◽  
Content Type ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

ABSTRACTAPlasmodium falciparumchimeric protein, PfMSP-Fu24, was constructed by genetically coupling immunodominant, conserved regions of two merozoite surface proteins, the 19-kDa region C-terminal region of merozoite surface protein 1 (PfMSP-119) and an 11-kDa conserved region of merozoite surface protein 3 (PfMSP-311), to augment the immunogenicity potential of these blood-stage malaria vaccine candidates. Here we describe an improved, efficient, and scalable process to produce high-quality PfMSP-Fu24. The chimeric protein was produced inEscherichia coliSHuffle T7 ExpresslysYcells that express disulfide isomerase DsbC. A two-step purification process comprising metal affinity followed by cation exchange chromatography was developed, and we were able to obtain PfMSP-Fu24with purity above 99% and with a considerable yield of 23 mg/liter. Immunogenicity of PfMSP-Fu24formulated with several adjuvants, including Adjuplex, Alhydrogel, Adjuphos, Alhydrogel plus glucopyranosyl lipid adjuvant, aqueous (GLA-AF), Adjuphos+GLA-AF, glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE), and Freund's adjuvant, was evaluated. PfMSP-Fu24formulated with GLA-SE and Freund's adjuvant in mice and with Alhydrogel and Freund's adjuvant in rabbits produced high titers of PfMSP-119and PfMSP-311-specific functional antibodies. Some of the adjuvant formulations induced inhibitory antibody responses and inhibitedin vitrogrowth ofP. falciparumparasites in the presence as well as in the absence of human monocytes. These results suggest that PfMSP-Fu24can form a constituent of a multistage malaria vaccine.

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