Genetic variation in the T-helper cell epitopic regions (Th2R and Th3R) of circumsporozoite protein of 135 Plasmodium falciparum isolates collected from different epidemic and endemic regions of India was studied. Variation in the Th2R and Th3R regions was found to exhibit restricted polymorphism and can be grouped. The variations were not regionally biased, as different isolates collected from different regions were found to belong to the same group. The Th2R and Th3R sequences were found to be linked in each isolate. Since the variations are regionally unbiased and restricted, the prototype variant from the groups could be included in a subunit polyvalent vaccine against sporozoites.
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http://dx.doi.org/10.1016/j.trstmh.2005.07.012 | DOI Listing |
Front Parasitol
April 2024
Centre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, Kenya.
The Circumsporozoite Protein (PfCSP) has been used in developing the RTS,S, and R21 malaria vaccines. However, genetic polymorphisms within compromise the effectiveness of the vaccine. Thus, it is essential to continuously assess the genetic diversity of , especially when deploying it across different geographical regions.
View Article and Find Full Text PDFmedRxiv
January 2024
National Institute for Medical Research, Dar es Salaam, Tanzania.
Background: In 2021 and 2023, the World Health Organization approved RTS, S/AS01 and R21/Matrix M malaria vaccines, respectively, for routine immunization of children in African countries with moderate to high transmission. These vaccines are made of circumsporozoite protein ( but polymorphisms in this gene raises concerns regarding strain-specific responses and the long-term efficacy of these vaccines. This study assessed the genetic diversity, population structure and signatures of selection among parasites from areas of different malaria transmission in mainland Tanzania, to generate baseline data before the introduction of the malaria vaccines in the country.
View Article and Find Full Text PDFPLoS Pathog
June 2023
Duke Global Health Institute, Duke University, Durham, North Carolina, United States of America.
A signature remains elusive of naturally-acquired immunity against Plasmodium falciparum. We identified P. falciparum in a 14-month cohort of 239 people in Kenya, genotyped at immunogenic parasite targets expressed in the pre-erythrocytic (circumsporozoite protein, CSP) and blood (apical membrane antigen 1, AMA-1) stages, and classified into epitope type based on variants in the DV10, Th2R, and Th3R epitopes in CSP and the c1L region of AMA-1.
View Article and Find Full Text PDFEMBO Mol Med
June 2023
B Cell Immunology, German Cancer Research Center, Heidelberg, Germany.
Human monoclonal antibodies (mAbs) against the central repeat and junction domain of Plasmodium falciparum circumsporozoite protein (PfCSP) have been studied extensively to guide malaria vaccine design compared to antibodies against the PfCSP C terminus. Here, we describe the molecular characteristics and protective potential of 73 germline and mutated human mAbs against the highly immunogenic PfCSP C-terminal domain. Two mAbs recognized linear epitopes in the C-terminal linker with sequence similarity to repeat and junction motifs, whereas all others targeted conformational epitopes in the α-thrombospondin repeat (α-TSR) domain.
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