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Antibody-Mediated and Cellular Immune Responses Induced in Naive Volunteers by Vaccination with Long Synthetic Peptides Derived from the Plasmodium vivax Circumsporozoite Protein

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  • Instituto de Inmunología, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia; Bio-Medical Parasitology Unit, Institut Pasteur, Paris, France; Biochemistry Institute, University of Lausanne, Lausanne, Switzerland

Plasmodium vivax circumsporozoite (CS) protein is a leading malaria vaccine candidate. We describe the characterization of specific immune responses induced in 21 malaria-naive volunteers vaccinated with long synthetic peptides derived from the CS protein formulated in Montanide ISA 720. Both antibody- and cell-mediated immune responses were analyzed. Antibodies were predominantly of IgG1 and IgG3 isotypes, recognized parasite proteins on the immunofluorescent antibody test, and partially blocked sporozoite invasion of hepatoma cell lines in vitro. Peripheral blood mononuclear cells from most volunteers (94%) showed IFN-γ production in vitro upon stimulation with both long signal peptide and short peptides containing CD8+ T-cell epitopes. The relatively limited sample size did not allow conclusions about HLA associations with the immune responses observed. In summary, the inherent safety and tolerability together with strong antibody responses, invasion blocking activity, and the IFN-γ production induced by these vaccine candidates warrants further testing in a phase II clinical trial.

Author Notes

*Address correspondence to Sócrates Herrera, Malaria Vaccine and Drug Development Center, Carrera 37 - 2Bis No. 5E - 08, Cali, Colombia. E-mail: sherrera@inmuno.org

Financial support: This work was supported by grants from the Instituto Colombiano “Francisco José de Caldas” para la Ciencia y la Tecnología COLCIENCIAS, the Colombian Ministry for Social Protection (contract no. 216-2006) and the Health Department of the Valle del Cauca, Cali, Colombia. The UNDP/World Bank/World Health Organization, Special Programme for Research and Training in Tropical Diseases (WHO/TDR) provided us with valuable advice and clinical monitoring. This study was supported by the provision of facilities by the Tropical Medicine Research Center (TMRC-Cali) (NIAID contract no. 49486-01). R. Palacios was supported by a student grant from the Brazilian Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Authors' addresses: Myriam Arévalo-Herrera, Liliana Soto, Blanca Liliana Perlaza, Nora Céspedes, Omaira Vera, Ana Milena Lenis, Anilza Bonelo, and Sócrates Herrera, Instituto de Inmunología, Edificio de Microbiología, Facultad de Salud, Universidad del Valle and Centro Internacional de Vacunas, Cali, Colombia, E-mails: marevalo@inmuno.org, lsoto@inmuno.org, bperlaza@inmuno.org, ncespedes@inmuno.org, ovlizcano@gmail.com, ana_lenis@yahoo.com, anbonelo@yahoo.com, and sherrera@inmuno.org. Giampietro Corradin, Biochemistry Institute, University of Lausanne, Lausanne, Switzerland, E-mail: giampietro.corradin@unil.ch.

Reprint requests: Sócrates Herrera, Malaria Vaccine and Drug Development Center, Carrera 37 - 2Bis No. 5E - 08, Cali, Colombia, E-mail: sherrera@inmuno.org.

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