scholarly journals Extent of polymorphism and selection pressure on the Trypanosoma cruzi vaccine candidate antigen Tc24

2020 ◽  
Vol 13 (10) ◽  
pp. 2663-2672
Author(s):  
Audrey Arnal ◽  
Liliana Villanueva‐Lizama ◽  
Christian Teh‐Poot ◽  
Claudia Herrera ◽  
Eric Dumonteil
Cytokine ◽  
2015 ◽  
Vol 74 (2) ◽  
pp. 273-278 ◽  
Author(s):  
Franciele Maira Moreira Batista Tomaz ◽  
Adriana Antônia da Cruz Furini ◽  
Marcela Petrolini Capobianco ◽  
Marinete Marins Póvoa ◽  
Pamella Cristina Alves Trindade ◽  
...  

2014 ◽  
Vol 9 (11) ◽  
pp. 1435-1445 ◽  
Author(s):  
Nadja Voepel ◽  
Alexander Boes ◽  
Güven Edgue ◽  
Veronique Beiss ◽  
Stephanie Kapelski ◽  
...  

2013 ◽  
Vol 81 (11) ◽  
pp. 4290-4298 ◽  
Author(s):  
Daisuke Ito ◽  
Tomoyuki Hasegawa ◽  
Kazutoyo Miura ◽  
Tsutomu Yamasaki ◽  
Thangavelu U. Arumugam ◽  
...  

ABSTRACTErythrocyte invasion by merozoites is an obligatory stage ofPlasmodiuminfection and is essential to disease progression. Proteins in the apical organelles of merozoites mediate the invasion of erythrocytes and are potential malaria vaccine candidates. Rhoptry-associated, leucine zipper-like protein 1 (RALP1) ofPlasmodium falciparumwas previously found to be specifically expressed in schizont stages and localized to the rhoptries of merozoites by immunofluorescence assay (IFA). Also, RALP1 has been refractory to gene knockout attempts, suggesting that it is essential for blood-stage parasite survival. These characteristics suggest that RALP1 can be a potential blood-stage vaccine candidate antigen, and here we assessed its potential in this regard. Antibodies were raised against recombinant RALP1 proteins synthesized by using the wheat germ cell-free system. Immunoelectron microscopy demonstrated for the first time that RALP1 is a rhoptry neck protein of merozoites. Moreover, our IFA data showed that RALP1 translocates from the rhoptry neck to the moving junction during merozoite invasion. Growth and invasion inhibition assays revealed that anti-RALP1 antibodies inhibit the invasion of erythrocytes by merozoites. The findings that RALP1 possesses an erythrocyte-binding epitope in the C-terminal region and that anti-RALP1 antibodies disrupt tight-junction formation, are evidence that RALP1 plays an important role during merozoite invasion of erythrocytes. In addition, human sera collected from areas in Thailand and Mali where malaria is endemic recognized this protein. Overall, our findings indicate that RALP1 is a rhoptry neck erythrocyte-binding protein and that it qualifies as a potential blood-stage vaccine candidate.


2001 ◽  
Vol 69 (9) ◽  
pp. 5464-5470 ◽  
Author(s):  
Sheetij Dutta ◽  
Lisa A. Ware ◽  
Arnoldo Barbosa ◽  
Christian F. Ockenhouse ◽  
David E. Lanar

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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