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circumsporozoite protein

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

February 23, 2021 - 13:06 -- Open Access
Singer M, Frischknecht F
Cell Microbiol. 2021 Feb 18:e13321

The 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. Yet, how CSP facilitates sporozoite formation, oocyst egress and hepatocyte specific invasion is still not fully understood.

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

January 27, 2021 - 10:04 -- Open Access
Jelínková L, Jhun H, Eaton A, Petrovsky N, Zavala F, Chackerian B
NPJ Vaccines. 2021 Jan 21;6(1):13

A 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.

Enhancing durability of CIS43 monoclonal antibody by Fc mutation or AAV delivery for malaria prevention

December 23, 2020 - 08:35 -- Open Access
Kielau Kisalu N, Da Silva Pereira L, Ernste KJ, Flores-Garcia Y, Idris AH, Asokan M, Dillon M, MacDonald S, Shi W, Chen X, Pegu A, Schön A, Zavala F, Balazs AB, Francica JR, Seder RA
JCI Insight. 2020 Dec 17:143958

CIS43 is a potent neutralizing human monoclonal antibody (mAb) that targets a highly conserved 'junctional' epitope in the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP). Enhancing the durability of CIS43 in vivo will be important for clinical translation. Here, two approaches were used to improve the durability of CIS43 in vivo while maintaining potent neutralization.

Structural ordering of the Plasmodium berghei circumsporozoite protein repeats by inhibitory antibody 3D11

December 3, 2020 - 12:17 -- Open Access
Kucharska I, Thai E, Srivastava A, Rubinstein JL, Pomès R, Julien JP
Elife. 2020 Nov 30;9:e59018

Plasmodium sporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, and the partial efficacy of RTS,S/AS01 - the leading malaria vaccine against P. falciparum (Pf) - has been associated with the humoral response against the repeats.

Population genetic analysis of the Plasmodium falciparum circumsporozoite protein in two distinct ecological regions in Ghana

December 2, 2020 - 07:45 -- Open Access
Elikplim A. Amegashie, Lucas Amenga-Etego, Courage Adobor, Peter Ogoti, Kevin Mbogo, Alfred Amambua-Ngwa and Anita Ghansah
Malaria Journal 2020 19:437, 27 November 2020

Extensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/AS01 vaccine. The transmission intensity and rates of recombination within and between populations influence the extent of its genetic diversity. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria-endemic areas such as Ghana.

Genetic polymorphism and natural selection of circumsporozoite protein in Myanmar Plasmodium vivax

September 8, 2020 - 11:46 -- Open Access
Tuấn Cường Võ, Hương Giang Lê, Jung-Mi Kang, Mya Moe, Haung Naw, Moe Kyaw Myint, Jinyoung Lee, Woon-Mok Sohn, Tong-Soo Kim and Byoung-Kuk Na
Malaria Journal 2020 19:303, 4 September 2020

Circumsporozoite surface protein (CSP) of malaria parasites has been recognized as one of the leading vaccine candidates. Clinical trials of vaccines for vivax malaria incorporating Plasmodium vivax CSP (PvCSP) have demonstrated their effectiveness in preventing malaria, at least in part. However, genetic diversity of pvcsp in the natural population remains a major concern.

Recombinant Plasmodium vivax circumsporozoite surface protein allelic variants: antibody recognition by individuals from three communities in the Brazilian Amazon

August 24, 2020 - 15:18 -- Open Access
Soares IF, López-Camacho C, Lima-Junior JDC, et al.
Sci Rep. 2020 Aug 20;10(1):14020

Circumsporozoite protein (CSP) variants of P. vivax, besides having variations in the protein repetitive portion, can differ from each other in aspects such as geographical distribution, intensity of transmission, vectorial competence and immune response. Such aspects must be considered to P. vivax vaccine development. Therefore, we evaluated the immunogenicity of novel recombinant proteins corresponding to each of the three P. vivax allelic variants (VK210, VK247 and P. vivax-like) and of the C-terminal region (shared by all PvCSP variants) in naturally malaria-exposed populations of Brazilian Amazon.

Polymorphism in the IL-1β promoter is associated with IgG antibody response to circumsporozoite protein repeats of Plasmodium vivax

August 10, 2020 - 15:58 -- Open Access
Capobianco MP, Cassiano GC, Machado RLD, et al.
Trans R Soc Trop Med Hyg. 2020 Aug 7:traa055

It is well established that infection by Plasmodium vivax is a result of host-parasite interactions. In the present study, association with the IL1/IL2 cytokine profiles, anticircumsporozoite protein antibody levels and parasitic loads was evaluated in individuals naturally infected with P. vivax in an endemic area of the Brazilian Amazon.

NOT Open Access | The importance of the immunodominant CD8+ T cell epitope of Plasmodium berghei circumsporozoite protein in parasite- and vaccine-induced protection

July 28, 2020 - 14:48 -- NOT Open Access
Gibbins MP, Müller K, Glover M, Liu J, Putrianti ED, Bauza K, Reyes-Sandoval A, Matuschewski K, Silvie O, Hafalla JCR
Infect Immun. 2020 Jul 27:IAI.00383-20

The circumsporozoite protein (CSP) builds up the surface coat of sporozoites and is the leading malaria pre-erythrocytic-stage vaccine candidate. CSP has been shown to induce robust CD8+ T cell responses that are capable of eliminating developing parasites in hepatocytes resulting in protective immunity. In this study, we characterised the importance of the immunodominant CSP-derived epitope, SYIPSAEKI, of Plasmodium berghei in both sporozoite- and vaccine-induced protection in murine infection models.

Genetic polymorphism of Plasmodium falciparum circumsporozoite protein on Bioko Island, Equatorial Guinea and global comparative analysis

July 14, 2020 - 09:34 -- Open Access
Hui-Ying Huang, Xue-Yan Liang, Min Lin, et al.
Malaria Journal 2020 19:245, 13 July 2020

Plasmodium falciparum circumsporozoite protein (PfCSP) is a potential malaria vaccine candidate, but various polymorphisms of the pfcsp gene among global P. falciparum population become the major barrier to the effectiveness of vaccines. This study aimed to investigate the genetic polymorphisms and natural selection of pfcsp in Bioko and the comparison among global P. falciparum population.


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