Phase I Safety and Immunogenicity Trial of Plasmodium vivax CS Derived Long Synthetic Peptides Adjuvanted with Montanide ISA 720 or Montanide ISA 51

Sócrates Herrera Instituto de Inmunología, Facultad de Salud, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia; Centro Médico Imbanaco, Cali, Colombia; Instituto de Investigaciones, Fundación Clínica Valle del Lili, Cali, Colombia; Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, Brazil; Family Health International, Durham, North Carolina; Biochemistry Institute, University of Lausanne, Epalinges, Switzerland

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Olga Lucía Fernández Instituto de Inmunología, Facultad de Salud, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia; Centro Médico Imbanaco, Cali, Colombia; Instituto de Investigaciones, Fundación Clínica Valle del Lili, Cali, Colombia; Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, Brazil; Family Health International, Durham, North Carolina; Biochemistry Institute, University of Lausanne, Epalinges, Switzerland

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Omaira Vera Instituto de Inmunología, Facultad de Salud, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia; Centro Médico Imbanaco, Cali, Colombia; Instituto de Investigaciones, Fundación Clínica Valle del Lili, Cali, Colombia; Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, Brazil; Family Health International, Durham, North Carolina; Biochemistry Institute, University of Lausanne, Epalinges, Switzerland

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William Cárdenas Instituto de Inmunología, Facultad de Salud, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia; Centro Médico Imbanaco, Cali, Colombia; Instituto de Investigaciones, Fundación Clínica Valle del Lili, Cali, Colombia; Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, Brazil; Family Health International, Durham, North Carolina; Biochemistry Institute, University of Lausanne, Epalinges, Switzerland

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Oscar Ramírez Instituto de Inmunología, Facultad de Salud, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia; Centro Médico Imbanaco, Cali, Colombia; Instituto de Investigaciones, Fundación Clínica Valle del Lili, Cali, Colombia; Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, Brazil; Family Health International, Durham, North Carolina; Biochemistry Institute, University of Lausanne, Epalinges, Switzerland

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Ricardo Palacios Instituto de Inmunología, Facultad de Salud, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia; Centro Médico Imbanaco, Cali, Colombia; Instituto de Investigaciones, Fundación Clínica Valle del Lili, Cali, Colombia; Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, Brazil; Family Health International, Durham, North Carolina; Biochemistry Institute, University of Lausanne, Epalinges, Switzerland

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Mario Chen-Mok Instituto de Inmunología, Facultad de Salud, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia; Centro Médico Imbanaco, Cali, Colombia; Instituto de Investigaciones, Fundación Clínica Valle del Lili, Cali, Colombia; Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, Brazil; Family Health International, Durham, North Carolina; Biochemistry Institute, University of Lausanne, Epalinges, Switzerland

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Giampietro Corradin Instituto de Inmunología, Facultad de Salud, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia; Centro Médico Imbanaco, Cali, Colombia; Instituto de Investigaciones, Fundación Clínica Valle del Lili, Cali, Colombia; Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, Brazil; Family Health International, Durham, North Carolina; Biochemistry Institute, University of Lausanne, Epalinges, Switzerland

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Myriam Arévalo-Herrera Instituto de Inmunología, Facultad de Salud, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia; Centro Médico Imbanaco, Cali, Colombia; Instituto de Investigaciones, Fundación Clínica Valle del Lili, Cali, Colombia; Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, Brazil; Family Health International, Durham, North Carolina; Biochemistry Institute, University of Lausanne, Epalinges, Switzerland

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We assessed the safety, tolerability, and immunogenicity of a mixture of three synthetic peptides derived from the Plasmodium vivax circumsporozoite protein formulated in Montanide ISA 720 or Montanide ISA 51. Forty healthy malaria-naive volunteers were allocated to five experimental groups (A–E): four groups (A–D) were immunized intramuscularly with 50 and 100 μg/dose injections of a mixture of N, R, and C peptides formulated in the two different adjuvants at 0, 2, and 4 months and one group was administered placebo. Vaccines were immunogenic, safe, well tolerated, and no serious adverse events related to the vaccine occurred. Seroconversion occurred in > 90% of the vaccines and antibodies recognized the sporozoite protein on immunofluorescent antibody test. Vaccines in Montanide ISA 51 showed a higher sporozoite protein recognition and interferon production. Results encourage further testing of the vaccine protective efficacy.

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 World Health Organization Initiative for Vaccine Research (grant no. LA35735G), National Institute of Allergy and Infectious Diseases (NIAID grant no. 49486/TMRC), Colombian National Research Council, COLCIENCIAS (contract no. 487-2003), the Colombian Ministry for Social Protection (conv. 255-2004), and the Malaria Vaccine and Drug Development Center Foundation. Ricardo Palacios was supported by a studentship grant from the Brazilian Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq and Mario Chen-Mok by the National Institutes of Health (NIH contract no. NIH/NO1-AI-05403).

Authors' addresses: Sócrates Herrera, Olga Lucía Fernández, Omaira Vera, and Myriam Arévalo-Herrera, Instituto de Inmunología, Facultad de Salud, Universidad del Valle, Cali, Colombia and Malaria Vaccine and Drug Development Center, Cali, Colombia, E-mails: sherrera@inmuno.org, olgalufe@yahoo.com, ovlizcano@gmail.com, and marevalo@inmuno.org. William Cárdenas, Centro Médico Imbanaco, Unidad de Medicina Interna y de Epidemiología Clínica, Cali, Colombia, E-mail: cardenasnino@gmail.com. Oscar Ramírez, Fundación Clínica Valle del Lili, Cali, Colombia, E-mail: oramirez@fcvl.org. Ricardo Palacios, Division of Infectious Diseases, Federal University of São Paulo, Rua Napoleao de Barros, São Paulo, Brazil, E-mail: ricardopalacios@gmx.net. Mario Chen-Mok, Family Health International, Durham, NC, E-mail: mchen@fhi.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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