- Introduction
- Materials and Methods
- Blood samples.
- Peptides.
- Total IgG to long, overlapping, and short peptides within N and C regions.
- IgG isotypes.
- Immunofluorescent antibody test (IFAT).
- Inhibition of sporozoite invasion (ISI) assay.
- Enzyme-linked immunosorbent spot (ELIspot) assay for enumeration of peptide-specific IFN-γ-secreting cells.
- HLA determination.
- Results
- Discussion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
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Mendis K, Sina BJ, Marchesini P, Carter R, 2001. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg 64: 97–106.
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Clyde DF, 1990. Immunity to falciparum and vivax malaria induced by irradiated sporozoites: a review of the University of Maryland studies, 1971–75. Bull World Health Organ 68 (Suppl): 9–12.
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Herrington D, Davis J, Nardin E, Beier M, Cortese J, Eddy H, Losonsky G, Hollingdale M, Sztein M, Levine M, Nussenzweig RS, Clyde D, Edelman R, 1991. Successful immunization of humans with irradiated malaria sporozoites: humoral and cellular responses of the protected individuals. Am J Trop Med Hyg 45: 539–547.
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Sharma S, Pathak S, 2008. Malaria vaccine: a current perspective. J Vector Borne Dis 45: 1–20.
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Nardin E, Zavala F, Nussenzweig V, Nussenzweig RS, 1999. Pre-erythrocytic malaria vaccine: mechanisms of protective immunity and human vaccine trials. Parassitologia 41: 397–402.
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Schofield L, Villaquiran J, Ferreira A, Schellekens H, Nussenzweig R, Nussenzweig V, 1987. Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature 330: 664–666.
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Doolan DL, Martinez-Alier N, 2006. Immune response to pre-erythrocytic stages of malaria parasites. Curr Mol Med 6: 169–185.
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Mellouk S, Green SJ, Nacy CA, Hoffman SL, 1991. IFN-gamma inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocytes by an L-arginine-dependent effector mechanism. J Immunol 146: 3971–3976.
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Egan JE, Weber JL, Ballou WR, Hollingdale MR, Majarian WR, Gordon DM, Maloy WL, Hoffman SL, Wirtz RA, Schneider I, Woollett GR, Young JF, Hockmeyer WT, 1987. Efficacy of murine malaria sporozoite vaccines: implications for human vaccine development. Science 236: 453–456.
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Stoute JA, Kester KE, Krzych U, Wellde BT, Hall T, White K, Glenn G, Ockenhouse CF, Garcon N, Schwenk R, Lanar DE, Sun P, Momin P, Wirtz RA, Golenda C, Slaoui M, Wortmann G, Holland C, Dowler M, Cohen J, Ballou WR, 1998. Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine. J Infect Dis 178: 1139–1144.
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Aponte JJ, Aide P, Renom M, Mandomando I, Bassat Q, Sacarlal J, Manaca MN, Lafuente S, Barbosa A, Leach A, Lievens M, Vekemans J, Sigauque B, Dubois MC, Demoitie MA, Sillman M, Savarese B, McNeil JG, Macete E, Ballou WR, Cohen J, Alonso PL, 2007. Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial. Lancet 370: 1543–1551.
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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
Myriam Arévalo-Herrera
Myriam Arévalo-Herrera
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
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Liliana Soto
Liliana Soto
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
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Blanca Liliana Perlaza
Blanca Liliana Perlaza
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
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Nora Céspedes
Nora Céspedes
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
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Omaira Vera
Omaira Vera
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
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Ana Milena Lenis
Ana Milena Lenis
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
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Anilza Bonelo
Anilza Bonelo
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
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Giampietro Corradin
Giampietro Corradin
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
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Sócrates Herrera
Sócrates Herrera
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
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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
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.
- Introduction
- Materials and Methods
- Blood samples.
- Peptides.
- Total IgG to long, overlapping, and short peptides within N and C regions.
- IgG isotypes.
- Immunofluorescent antibody test (IFAT).
- Inhibition of sporozoite invasion (ISI) assay.
- Enzyme-linked immunosorbent spot (ELIspot) assay for enumeration of peptide-specific IFN-γ-secreting cells.
- HLA determination.
- Results
- Discussion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Mendis K, Sina BJ, Marchesini P, Carter R, 2001. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg 64: 97–106.
-
2.
Clyde DF, 1990. Immunity to falciparum and vivax malaria induced by irradiated sporozoites: a review of the University of Maryland studies, 1971–75. Bull World Health Organ 68 (Suppl): 9–12.
-
3.
Herrington D, Davis J, Nardin E, Beier M, Cortese J, Eddy H, Losonsky G, Hollingdale M, Sztein M, Levine M, Nussenzweig RS, Clyde D, Edelman R, 1991. Successful immunization of humans with irradiated malaria sporozoites: humoral and cellular responses of the protected individuals. Am J Trop Med Hyg 45: 539–547.
-
4.
Hoffman SL, Goh LM, Luke TC, Schneider I, Le TP, Doolan DL, Sacci J, de la Vega P, Dowler M, Paul C, Gordon DM, Stoute JA, Church LW, Sedegah M, Heppner DG, Ballou WR, Richie TL, 2002. Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites. J Infect Dis 185: 1155–1164.
-
5.
Hollingdale MR, Nardin EH, Tharavanij S, Schwartz AL, Nussenzweig RS, 1984. Inhibition of entry of Plasmodium falciparum and P. vivax sporozoites into cultured cells; an in vitro assay of protective antibodies. J Immunol 132: 909–913.
-
6.
Herrera S, Corradin G, Arévalo-Herrera M, 2007. An update on the search for a Plasmodium vivax vaccine. Trends Parasitol 23: 122–128.
-
7.
Sharma S, Pathak S, 2008. Malaria vaccine: a current perspective. J Vector Borne Dis 45: 1–20.
-
8.
Nardin E, Zavala F, Nussenzweig V, Nussenzweig RS, 1999. Pre-erythrocytic malaria vaccine: mechanisms of protective immunity and human vaccine trials. Parassitologia 41: 397–402.
-
9.
Schofield L, Villaquiran J, Ferreira A, Schellekens H, Nussenzweig R, Nussenzweig V, 1987. Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature 330: 664–666.
-
10.
Doolan DL, Martinez-Alier N, 2006. Immune response to pre-erythrocytic stages of malaria parasites. Curr Mol Med 6: 169–185.
-
11.
Mellouk S, Green SJ, Nacy CA, Hoffman SL, 1991. IFN-gamma inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocytes by an L-arginine-dependent effector mechanism. J Immunol 146: 3971–3976.
-
12.
Mellouk S, Maheshwari RK, Rhodes-Feuillette A, Beaudoin RL, Berbiguier N, Matile H, Miltgen F, Landau I, Pied S, Chigot JP, Friedman RM, Mazier D, 1987. Inhibitory activity of interferons and interleukin 1 on the development of Plasmodium falciparum in human hepatocyte cultures. J Immunol 139: 4192–4195.
-
13.
Egan JE, Weber JL, Ballou WR, Hollingdale MR, Majarian WR, Gordon DM, Maloy WL, Hoffman SL, Wirtz RA, Schneider I, Woollett GR, Young JF, Hockmeyer WT, 1987. Efficacy of murine malaria sporozoite vaccines: implications for human vaccine development. Science 236: 453–456.
-
14.
Graves P, Gelband H, 2003. Vaccines for preventing malaria. Cochrane Database Syst Rev CD000129.
-
15.
Moorthy V, Smith PG, Kieny MP, 2009. A vaccine against malaria: a substantial step forward. Lancet 373: 1411–1412.
-
16.
Stoute JA, Kester KE, Krzych U, Wellde BT, Hall T, White K, Glenn G, Ockenhouse CF, Garcon N, Schwenk R, Lanar DE, Sun P, Momin P, Wirtz RA, Golenda C, Slaoui M, Wortmann G, Holland C, Dowler M, Cohen J, Ballou WR, 1998. Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine. J Infect Dis 178: 1139–1144.
-
17.
Bojang KA, Milligan PJ, Pinder M, Vigneron L, Alloueche A, Kester KE, Ballou WR, Conway DJ, Reece WH, Gothard P, Yamuah L, Delchambre M, Voss G, Greenwood BM, Hill A, McAdam KP, Tornieporth N, Cohen JD, Doherty T, 2001. Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet 358: 1927–1934.
-
18.
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