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IMMUNOGENICITY AND PROTECTIVE EFFICACY OF RECOMBINANT VACCINE BASED ON THE RECEPTOR-BINDING DOMAIN OF THE PLASMODIUM VIVAX DUFFY BINDING PROTEIN IN AOTUS MONKEYS

Invasion of human erythrocytes by Plasmodium vivax requires interaction between Duffy binding protein (PvDBP) and the Duffy blood group antigen. The receptor-binding domain of PvDBP lies in a conserved N-terminal, cysteine-rich region, region II (PvRII). PvRII is a valuable malaria subunit vaccine candidate for asexual blood stages. We have evaluated in Aotus monkeys the immunogenicity and protective efficacy of recombinant PvRII formulated in Freund’s and Montanide ISA720 adjuvants. Specific antibody titers were determined by an enzyme-linked immunosorbent assay after each of three doses of 50 µg of protein administered by the subcutaneous route. Immunization with PvRII formulated in Freund’s adjuvant yielded higher antibody titers than immunization with the Montanide ISA720 formulation and offered partial protection. Although the Montanide ISA720 formulation was immunogenic, it did not provide any protection. Given the immunogenicity and partial protection observed, further studies are needed to optimize the PvRII vaccine formulation with adjuvants suitable for human use.

Received April 12, 2005. Accepted for publication August 10, 2005.

Acknowledgments: We thank Claudia Salas (Fundación Centro de Primates) for technical support, Mario Chen (Family Health International) for assistance in statistical analyses, and Elisabeth Robinson for critically reading the manuscript. Chetan E. Chitnis is an International Research Scholar of the Howard Hughes Medical Institute and International Senior Research Fellow of The Wellcome Trust, United Kingdom.

Financial support: This work was supported by the National Institute of Allergy and Infections Diseases (Tropical Medicine Research Centers contract no. AI49486-02, Family Health International Contract NIH/NO1-AI-05403, and a grant to Chetan E. Chitnis from the World Health Organization Special Program in Tropical Diseases Research.

^* Address correspondence to Myriam Arévalo-Herrera, Malaria Vaccine and Drug Testing Center, Cra 35 No. 4A-53, Cali, Colombia. E-mail: marevalo{at}immuno.org

Authors’ addresses: Myriam Arévalo-Herrera, Angélica Castellanos, and Socrates Herrera, Instituto de Inmunología de la Universidad del Valle, Calle 4B 36-00, Edificio de Microbiología, Tercer Piso, Facultad de Salud, Universidad del Valle Sede San Fernado, AA 25574, Cali, Colombia, Telephone: 57-2-558-1931, Fax: 57-2-557-0449 and Malaria Vaccine Development Center, AA 26020, Cali, Colombia, Telephone: 57-2-558-3937, Fax: 57-2-556-0141, E-mail: marevalo{at}inmuno.org. Syed S. Yazdani, Ahmad Rushdi Shakri, Chetan E. Chitnis, Malaria Research Group, International Centre for Genetic Engineering and Biotechnology, Campus Aruna Asaf Ali Marg, 110067, New Delhi, India, Telephone: 91-11-2619-5007, Fax: 91-11-2616-2316. Rosalie Dominik, Family Health International, 2224 E. NC Highway 54, Durham, NC 27713, Telephone: 919-544-7040, Fax: 1-919-544-7261.

Reprint requests: Myriam Arévalo-Herrera, Malaria Vaccine and Drug Testing Center, Cra 35 No. 4A-53, Cali, Colombia, E-mail: marevalo{at}inmuno.org