Further Studies on the Immunization of Saimiri sciureus boliviensis with Recombinant Vaccines Based on the Circumsporozoite Protein of Plasmodium vivax

William E. Collins Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Ruth S. Nussenzweig Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Trenton K. Ruebush II Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Ian C. Bathurst Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Elizabeth H. Nardin Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Helen L. Gibson Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Gary H. Campbell Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Philip J. Barr Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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J. Roger Broderson Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Jimmie C. Skinner Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Valerie K. Filipski Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Peggy S. Stanfill Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Jacquelin M. Roberts Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Carla L. Wilson Division of Parasitic Diseases and Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, New York University Medical Center, Chiron Corporation, Atlanta, Georgia

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Reported are the results of a trial in squirrel monkeys of 2 Plasmodium vivax malaria vaccine candidates based on the circumsporozoite (CS) protein, namely, rPvCs-2 and rPvCS-3. Compared with an earlier recombinant P. vivax CS construct, rPvCS-1, rPvCS-2 has an additional 24 amino acids at the C-terminal, which includes the thrombospondin region of homology and a putative T cell epitope. The rPvCS-3 was generated from a chemically synthesized gene that contained an additional 54 amino acids at the amino terminus and terminates at the same carboxy-terminal amino acid as rPvCS-2. In addition, rPvCS-3 contained only 1 each of the repeat sequences DRADGQPAG and DRAAGQPAG. Both antigens were administered with alum as adjuvant. Neither formulation caused toxic side effects and both recombinant molecules induced high antibody titers. Two monkeys were protected against sporozoite challenge by immunization with rPvCS-2 antigen, while none of the rPvCS-3 immunized animals displayed any degree of protection. While there was no correlation between protection and antibody titer or the in vitro proliferation of lymphocytes in response to the antigens, this is further evidence to support the role of the repeating epitopes in generating protective immunity.

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