scholarly journals Fluorescent tagging of Plasmodium circumsporozoite protein allows imaging of sporozoite formation but blocks egress from oocysts

2021 ◽  
Vol 23 (5) ◽  
Author(s):  
Mirko Singer ◽  
Friedrich Frischknecht
Keyword(s):  
Circumsporozoite Protein ◽  
Fluorescent Tagging

scholarly journals Fluorescent tagging of Plasmodium circumsporozoite protein allows imaging of sporozoite formation but blocks egress from oocysts

2020 ◽  
Author(s):  
Mirko Singer ◽  
Friedrich Frischknecht
Keyword(s):  
Fluorescent Protein ◽  
Surface Protein ◽  
Dominant Negative ◽  
Circumsporozoite Protein ◽  
Negative Function ◽  
Mammalian Liver ◽  
Parasite Replication ◽  
Fluorescent Tagging ◽  
Green Fluorescent ◽  
Major Surface

AbstractThe circumsporozoite protein, CSP is the major surface protein of Plasmodium sporozoites, the form of malaria parasites transmitted by mosquitoes. CSP is involved in sporozoite formation within and egress from oocysts, entry into mosquito salivary glands and mammalian liver as well as migration in the skin. Antibodies against CSP can stop infection prior to the first round of parasite replication in the liver. CSP consists of different domains and is proteolytically cleaved prior to hepatocyte invasion. Part of CSP has been developed into a licensed vaccine against malaria. Yet, how CSP facilitates sporozoite formation, oocyst egress and hepatocyte specific invasion is still not fully understood. Here, we generated a series of parasites expressing full-length versions of CSP as fusion proteins with the green fluorescent protein. This enabled the investigation of sporozoite formation in living oocysts and revealed a dominant negative function of some GFP-CSP fusions during sporozoite egress.

scholarly journals Diverse Antibody Responses to Conserved Structural Motifs in Plasmodium falciparum Circumsporozoite Protein

2020 ◽  
Vol 432 (4) ◽  
pp. 1048-1063 ◽  
Author(s):  
Tossapol Pholcharee ◽  
David Oyen ◽  
Jonathan L. Torres ◽  
Yevel Flores-Garcia ◽  
Gregory M. Martin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antibody Responses ◽  
Circumsporozoite Protein ◽  
Structural Motifs

scholarly journals In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Merricka C. Livingstone ◽  
Alexis A. Bitzer ◽  
Alish Giri ◽  
Kun Luo ◽  
Rajeshwer S. Sankhala ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Monoclonal Antibodies ◽  
Disease Burden ◽  
Vaccine Candidate ◽  
Specific Binding ◽  
Circumsporozoite Protein ◽  
Target Epitope ◽  
Selection Of

AbstractPlasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)n repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)n epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)n. In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.

scholarly journals An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lucie Jelínková ◽  
Hugo Jhun ◽  
Allison Eaton ◽  
Nikolai Petrovsky ◽  
Fidel Zavala ◽  
...  
Keyword(s):  
Mouse Model ◽  
Malaria Vaccine ◽  
High Titer ◽  
Circumsporozoite Protein ◽  
Infection Model ◽  
Vaccine Platform ◽  
Junctional Region ◽  
Mouse Infection Model ◽  
Virus Like Particle ◽  
Major Surface

AbstractA malaria vaccine that elicits long-lasting protection and is suitable for use in endemic areas remains urgently needed. Here, we assessed the immunogenicity and prophylactic efficacy of a vaccine targeting a recently described epitope on the major surface antigen on Plasmodium falciparum sporozoites, circumsporozoite protein (CSP). Using a virus-like particle (VLP)-based vaccine platform technology, we developed a vaccine that targets the junctional region between the N-terminal and central repeat regions of CSP. This region is recognized by monoclonal antibodies, including mAb CIS43, that have been shown to potently prevent liver invasion in animal models. We show that CIS43 VLPs elicit high-titer and long-lived anti-CSP antibody responses in mice and is immunogenic in non-human primates. In mice, vaccine immunogenicity was enhanced by using mixed adjuvant formulations. Immunization with CIS43 VLPs conferred partial protection from malaria infection in a mouse model, and passive transfer of serum from immunized macaques also inhibited parasite liver invasion in the mouse infection model. Our findings demonstrate that a Qβ VLP-based vaccine targeting the CIS43 epitope combined with various adjuvants is highly immunogenic in mice and macaques, elicits long-lasting anti-CSP antibodies, and inhibits parasite infection in a mouse model. Thus, the CIS43 VLP vaccine is a promising pre-erythrocytic malaria vaccine candidate.

Cytotoxic T cell reactivity and HLA-B35 binding of the variantPlasmodium falciparum circumsporozoite protein CD8+ CTL epitope in naturally exposed Kenyan adults

1997 ◽  
Vol 27 (8) ◽  
pp. 1952-1957 ◽  
Author(s):  
Venkatachalam Udhayakumar ◽  
John M. Ongecha ◽  
Ya-Ping Shi ◽  
Michael Aidoo ◽  
A. S. S. Orago ◽  
...  
Keyword(s):  
T Cell ◽  
Circumsporozoite Protein ◽  
Cytotoxic T Cell ◽  
Cell Reactivity ◽  
Ctl Epitope ◽  
T Cell Reactivity

scholarly journals Comparative population structure of Plasmodium falciparum circumsporozoite protein NANP repeat lengths in Lilongwe, Malawi

2013 ◽  
Vol 3 (1) ◽  
Author(s):  
Natalie M. Bowman ◽  
Seth Congdon ◽  
Tisungane Mvalo ◽  
Jaymin C. Patel ◽  
Veronica Escamilla ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Population Structure ◽  
Circumsporozoite Protein ◽  
Comparative Population

scholarly journals Antibodies to Plasmodium circumsporozoite protein (CSP) inhibit sporozoite's cell traversal activity

2012 ◽  
Vol 377 (1-2) ◽  
pp. 47-52 ◽  
Author(s):  
Satish Mishra ◽  
Ruth S. Nussenzweig ◽  
Victor Nussenzweig
Keyword(s):  
Circumsporozoite Protein
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