Nora Céspedes1, Eliécer Jiménez2, Mary Lopez-Perez3, Kelly Rubiano4, Ingrid Felger5, Pedro Alonso6, Myriam Arévalo-Herrera1, Giampietro Corradin7, Sócrates Herrera8. 1. Malaria Vaccine and Drug Development Center (MVDC), Carrera 37 2Bis No. 5E-08, A.A. 25574, Cali, Colombia; Faculty of Health, University of Valle, Calle 4B # 36-00, Cali, Colombia. 2. Malaria Vaccine and Drug Development Center (MVDC), Carrera 37 2Bis No. 5E-08, A.A. 25574, Cali, Colombia. 3. Malaria Vaccine and Drug Development Center (MVDC), Carrera 37 2Bis No. 5E-08, A.A. 25574, Cali, Colombia; Caucaseco Scientific Research Centre, A.A. 760042, Cali, Colombia. 4. Malaria Vaccine and Drug Development Center (MVDC), Carrera 37 2Bis No. 5E-08, A.A. 25574, Cali, Colombia; Fundación Centro de Primates, AA 26020 Cali, Colombia. 5. Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel, Switzerland. 6. Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain. 7. Biochemistry Department, University of Lausanne, 155 Ch. des Boveresses, 1066 Epalinges, Lausanne, Switzerland. 8. Malaria Vaccine and Drug Development Center (MVDC), Carrera 37 2Bis No. 5E-08, A.A. 25574, Cali, Colombia; Faculty of Health, University of Valle, Calle 4B # 36-00, Cali, Colombia. Electronic address: sherrera@inmuno.org.
Abstract
BACKGROUND: The circumsporozoite (CS) protein is a major malaria sporozoite surface antigen currently being considered as vaccine candidate. Plasmodium vivax CS (PvCS) protein comprises a dimorphic central repeat fragment flanked by conserved regions that contain functional domains involved in parasite invasion of host cells. The protein amino (N-terminal) flank has a cleavage region (region I), essential for proteolytic processing prior to parasite invasion of liver cells. METHODS: We have developed a 131-mer long synthetic polypeptide (LSP) named PvNR1R2 that includes the N-terminal flank and the two natural repeat variant regions known as VK210 and VK247. We studied the natural immune response to this region in human sera from different malaria-endemic areas and its immunogenicity in mice. RESULTS: PvNR1R2 was more frequently recognized by sera from Papua New Guinea (PNG) (83%) than by samples from Colombia (24%) when tested by ELISA. The polypeptide formulated in Montanide ISA51 adjuvant elicited strong antibody responses in both C3H and CB6F1 mice strains. Antibodies from immunized mice as well as affinity-purified human IgG reacted with native protein by IFA test. Moreover, mouse immune sera induced strong (90%) in vitro inhibition of sporozoite invasion (ISI) of hepatoma cell lines. CONCLUSIONS: These results encourage further studies in non-human primates to confirm the elicitation of sporozoite invasion blocking antibodies, to assess cell mediated immune responses and the protective efficacy of this polypeptide.
BACKGROUND: The circumsporozoite (CS) protein is a major malaria sporozoite surface antigen currently being considered as vaccine candidate. Plasmodium vivax CS (PvCS) protein comprises a dimorphic central repeat fragment flanked by conserved regions that contain functional domains involved in parasite invasion of host cells. The protein amino (N-terminal) flank has a cleavage region (region I), essential for proteolytic processing prior to parasite invasion of liver cells. METHODS: We have developed a 131-mer long synthetic polypeptide (LSP) named PvNR1R2 that includes the N-terminal flank and the two natural repeat variant regions known as VK210 and VK247. We studied the natural immune response to this region in human sera from different malaria-endemic areas and its immunogenicity in mice. RESULTS: PvNR1R2 was more frequently recognized by sera from Papua New Guinea (PNG) (83%) than by samples from Colombia (24%) when tested by ELISA. The polypeptide formulated in Montanide ISA51 adjuvant elicited strong antibody responses in both C3H and CB6F1 mice strains. Antibodies from immunized mice as well as affinity-purified human IgG reacted with native protein by IFA test. Moreover, mouse immune sera induced strong (90%) in vitro inhibition of sporozoite invasion (ISI) of hepatoma cell lines. CONCLUSIONS: These results encourage further studies in non-human primates to confirm the elicitation of sporozoite invasion blocking antibodies, to assess cell mediated immune responses and the protective efficacy of this polypeptide.
Authors: Rodrigo Nunes Rodrigues-da-Silva; João Hermínio Martins da Silva; Balwan Singh; Jianlin Jiang; Esmeralda V S Meyer; Fátima Santos; Dalma Maria Banic; Alberto Moreno; Mary R Galinski; Joseli Oliveira-Ferreira; Josué da Costa Lima-Junior Journal: PLoS One Date: 2016-01-20 Impact factor: 3.240
Authors: Lei Zhu; Sachel Mok; Mallika Imwong; Anchalee Jaidee; Bruce Russell; Francois Nosten; Nicholas P Day; Nicholas J White; Peter R Preiser; Zbynek Bozdech Journal: Sci Rep Date: 2016-02-09 Impact factor: 4.379
Authors: Ahmed M Salman; Eduardo Montoya-Díaz; Heather West; Amar Lall; Erwan Atcheson; Cesar Lopez-Camacho; Jai Ramesar; Karolis Bauza; Katharine A Collins; Florian Brod; Fernando Reis; Leontios Pappas; Lilia González-Cerón; Chris J Janse; Adrian V S Hill; Shahid M Khan; Arturo Reyes-Sandoval Journal: Sci Rep Date: 2017-04-18 Impact factor: 4.379