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SAFETY AND ELICITATION OF HUMORAL AND CELLULAR RESPONSES IN COLOMBIAN MALARIA-NAIVE VOLUNTEERS BY A PLASMODIUM VIVAX CIRCUMSPOROZOITE PROTEIN–DERIVED SYNTHETIC VACCINE

Substantial experimental evidence indicates that the Plasmodium circumsporozoite (CS) protein has great potential as a vaccine candidate. We tested the safety and immunogenicity of vaccines composed of P. vivax CS-derived synthetic peptides. Sixty-nine healthy, malaria-naive volunteers were randomized to receive three injections of placebo or synthetic proteins N, R, or C (10, 30, or 100 µg/dose) in a double-blinded fashion. Vaccines were well tolerated and no serious adverse events were observed. Peptides N and R elicited humoral responses at all doses; peptide C elicicted these responses only at doses of 30 and 100 µg. The N peptide at a dose of 100 µg elicited the greatest antibody response. Antibodies to the three peptides recognized P. vivax sporozoites in an immunofluorescent antibody test. Peripheral blood mononuclear cells from most immunized volunteers also produced interferon- upon peptide in vitro stimulation. These vaccines appear safe, well tolerated, and immunogenic in malaria-naive volunteers. Further optimization and development of this vaccine is being attempted to conduct phase II clinical trials.

Received April 12, 2005. Accepted for publication July 7, 2005.

Acknowledgments: We thank the study participants for their invaluable collaboration in the study; Mauricio León, Edna Galindo, Fabián Méndez, and Marisol Badiel for support; Luz Elena García for valuable assistance in the recruitment of volunteers; Antonio José Ramirez for assistance in the administrative management; Vincent Ganne, (Seppic Inc., Paris, France) for supplying the Montanide ISA 720 adjuvant; Luis Rodriguez for peptides synthesis and purification; Gloria Palma (COLCIENCIAS (Bogotá, Colombia) and William Rojas (Corporación de Investigaciones Biológicas, Medellín, Colombia) for participating in the Safety Monitoring Board; Elizabeth T. Robinson (Family Health International, (Research Triangle Park, NC) and Amy Burks for critically reading the manuscript.

Financial support: This work was supported by grants from the Instituto Colombiano Francisco Jose de Caldas para la Ciencia y la Tecnología (COLCIENCIAS), the Health Department of the Valle del Cauca, and the Tropical Medicine Research Center (TMRC-Cali) (National Institute of Allergy and Infectious Diseases contract no. 49486). The UNDP/World Bank/World Health Organization Special Program for Research, and Training in Tropical Diseases provided valuable advice and clinical monitoring. Ricardo Palacios is supported by a studentship grant from the Brazilian Conselho Nacional de Desenvolvimento Ceientifico e Tecnológico – CNPq. Mario Chen-Mok is supported by the National Institutes of Health (NIH contract no. NIH/NO1-AI-05403).

^* Address correspondence to Sócrates Herrera, Malaria Vaccine and Drug Development Center, Carrera 35 No. 4A-53, A.A. 25574, Cali, Colombia. E-mail: sherrera{at}inmuno.org

Authors’ addresses: Sócrates Herrera, Anilza Bonelo, Blanca Liliana Perlaza, Olga Fernández, Leonardo Victoria, Ana Milena Lenis, Liliana Soto, Hugo Hurtado, Lina Maria Acuña, and Myriam Arévalo-Herrera, Instituto de Inmunología, Universidad del Valle, Calle 4B No. 36-00, Facultad de Salud, A.A. 25574, Cali, Colombia, Telephone: 57-2-558-1931, Fax: 57-2-557-0449, and Malaria Vaccine and Drug Development Center, Carrera 35 No. 4A-53, A.A. 25574, Cali, Colombia, Telephone: 57-2-5583937, Fax: 57-2-5560141, E-mail: sherrera{at}inmuno.org. Juan Diego Vélez, Fundación Clínica Valle del Lili, Autopista Simón Bolivar, Carrera 98 No. 18-48, A.A. 020338, Cali, Colombia, Telephone: 57-2-331-9090. Ricardo Palacios, Division of Infectious Diseases, Federal University of Sao Paulo, Rua Napoleao de Barros, 715, Sao Paulo, CEP 040024-002, Brazil, Telephone: 55-11-55764357, Fax: 55-11-557745071. Mario Chen-Mok, Family Health International, Durham, NC 27713. Giampietro Corradin, Biochemistry Institute, University of Lausanne, 155 Ch. des Boveresses, 1066 Epalinges, Lausanne, Switzerland, Telephone: 41-21-6925701, Fax: 41-21-6925705.

Reprint requests: Sócrates Herrera, Malaria Vaccine and Drug Development Center, Carrera 35 No 4A-53, Cali, Colombia.

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