A universal vaccine candidate against Plasmodium vivax malaria confers protective immunity against the three PvCSP alleles.
Alba Marina Gimenez, Ahmed M Salman, Rodolfo F Marques, César López-Camacho, Kate Harrison, Young Chan Kim, Chris J Janse, Irene S Soares, Arturo Reyes-Sandoval
Author Information
Alba Marina Gimenez: Nuffield Department of Medicine, The Jenner Institute, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford, OX3 7BN, UK.
Ahmed M Salman: Nuffield Department of Medicine, The Jenner Institute, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford, OX3 7BN, UK.
Rodolfo F Marques: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
César López-Camacho: Nuffield Department of Medicine, The Jenner Institute, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford, OX3 7BN, UK.
Kate Harrison: Nuffield Department of Medicine, The Jenner Institute, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford, OX3 7BN, UK.
Young Chan Kim: Nuffield Department of Medicine, The Jenner Institute, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford, OX3 7BN, UK.
Chris J Janse: Department of Parasitology, Leiden Malaria Research Group, Center of Infectious Diseases, Leiden University Medical Center, (LUMC, L4-Q), Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Irene S Soares: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil. isoares@usp.br.
Arturo Reyes-Sandoval: Nuffield Department of Medicine, The Jenner Institute, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford, OX3 7BN, UK. arturo.reyes@ndm.ox.ac.uk.
Malaria is a highly prevalent parasitic disease in regions with tropical and subtropical climates worldwide. Among the species of Plasmodium causing human Malaria, P. vivax is the second most prevalent and the most geographically widespread species. A major target of a pre-erythrocytic vaccine is the P. vivax circumsporozoite protein (PvCSP). In previous studies, we fused two recombinant proteins representing three allelic variants of PvCSP (VK210, VK247 and P. vivax-like) to the mumps virus nucleocapsid protein to enhance immune responses against PvCSP. The objective of the present study was to evaluate the protective efficacy of these recombinants in mice challenged with transgenic P. berghei parasites expressing PvCSP allelic variants. Formulations containing Poly (I:C) or Montanide ISA720 as adjuvants elicited high and long-lasting IgG antibody titers specific to each PvCSP allelic variant. Immunized mice were challenged with two existing chimeric P. berghei parasite lines expressing PvCSP-VK210 and PvCSP-VK247. We also developed a novel chimeric line expressing the third allelic variant, PvCSP-P. vivax-like, as a new murine immunization-challenge model. Our formulations conferred partial protection (significant delay in the time to reach 1% parasitemia) against challenge with the three chimeric parasites. Our results provide insights into the development of a vaccine targeting multiple strains of P. vivax.
