Clinical expression and antigenic profiles of a Plasmodium vivax vaccine candidate: merozoite surface protein 7 (PvMSP-7)

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.

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

Infection and Immunity ◽

10.1128/iai.00645-20 ◽

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.

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The evolution and diversity of a low complexity vaccine candidate, merozoite surface protein 9 (MSP-9), in Plasmodium vivax and closely related species

Infection Genetics and Evolution ◽

10.1016/j.meegid.2013.09.011 ◽

2013 ◽

Vol 20 ◽

pp. 239-248 ◽

Cited By ~ 10

Author(s):

Stella M. Chenet ◽

M. Andreína Pacheco ◽

David J. Bacon ◽

William E. Collins ◽

John W. Barnwell ◽

...

Keyword(s):

Plasmodium Vivax ◽

Related Species ◽

Vaccine Candidate ◽

Surface Protein ◽

Low Complexity ◽

Merozoite Surface Protein ◽

Closely Related Species

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

Malaria Journal ◽

10.1186/s12936-019-3066-6 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 2

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.

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

Infection and Immunity ◽

10.1128/iai.01117-12 ◽

2013 ◽

Vol 81 (5) ◽

pp. 1585-1595 ◽

Cited By ~ 33

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.

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Genetic diversity of the malaria vaccine candidate merozoite surface protein 1 gene of Plasmodium vivax field isolates in Republic of Korea

Parasitology Research ◽

10.1007/s00436-011-2413-5 ◽

2011 ◽

Vol 109 (6) ◽

pp. 1571-1576 ◽

Cited By ~ 9

Author(s):

Eun-Taek Han ◽

Yue Wang ◽

Chae Seung Lim ◽

Jun Hwi Cho ◽

Jong-Yil Chai

Keyword(s):

Genetic Diversity ◽

Plasmodium Vivax ◽

Malaria Vaccine ◽

Vaccine Candidate ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Republic Of Korea ◽

Field Isolates ◽

Merozoite Surface Protein 1 ◽

Malaria Vaccine Candidate

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PvMSP8 as a Novel Plasmodium vivax Malaria Sero-Marker for the Peruvian Amazon

Pathogens ◽

10.3390/pathogens10030282 ◽

2021 ◽

Vol 10 (3) ◽

pp. 282

Author(s):

Elizabeth Villasis ◽

Katherine Garro ◽

Angel Rosas-Aguirre ◽

Pamela Rodriguez ◽

Jason Rosado ◽

...

Keyword(s):

Plasmodium Vivax ◽

Area Under The Curve ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Population Based ◽

Peruvian Amazon ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Malaria Exposure ◽

Plasmodium Vivax Malaria

The measurement of recent malaria exposure can support malaria control efforts. This study evaluated serological responses to an in-house Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) expressed in a Baculovirus system as sero-marker of recent exposure to P. vivax (Pv) in the Peruvian Amazon. In a first evaluation, IgGs against PvMSP8 and PvMSP10 proteins were measured by Luminex in a cohort of 422 Amazonian individuals with known history of Pv exposure (monthly data of infection status by qPCR and/or microscopy over five months). Both serological responses were able to discriminate between exposed and non-exposed individuals in a good manner, with slightly higher performance of anti-PvMSP10 IgGs (area under the curve AUC = 0.78 [95% CI = 0.72–0.83]) than anti-PvMSP8 IgGs (AUC = 0.72 [95% CI = 0.67–0.78]) (p = 0.01). In a second evaluation, the analysis by ELISA of 1251 plasma samples, collected during a population-based cross-sectional survey, confirmed the good performance of anti-PvMSP8 IgGs for discriminating between individuals with Pv infection at the time of survey and/or with antecedent of Pv in the past month (AUC = 0.79 [95% CI = 0.74–0.83]). Anti-PvMSP8 IgG antibodies can be considered as a good biomarker of recent Pv exposure in low-moderate transmission settings of the Peruvian Amazon.

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