A universal vaccine candidate against Plasmodium vivax malaria confers protective immunity against the three PvCSP alleles

Autor(es)

Gimenez, Alba Marina ^{[1, 2]} ; Salman, Ahmed M. ^[2] ; Marques, Rodolfo F. ^[1] ; Lopez-Camacho, Cesar ^[2] ; Harrison, Kate ^[2] ; Kim, Young Chan ^[2] ; Janse, Chris J. ^[3] ; Soares, Irene S. ^[1] ; Reyes-Sandoval, Arturo ^{[2, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, SP - Brazil

^[2] Univ Oxford, Jenner Inst, Nuffield Dept Med, Henry Wellcome Bldg Mol Physiol, Roosevelt Dr, Oxford OX3 7BN - England

^[3] Leiden Univ Med Ctr, Dept Parasitol, Leiden Malaria Res Grp, Ctr Infect Dis, L4-Q, Albinusdreef 2, NL-2333 ZA Leiden - Netherlands

^[4] Inst Politecnico Nacl, Unidad Adolfo Lopez Mateos, Ave Luis Enrique Erro S-N, Mexico City 07738, DF - Mexico

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 11, n. 1 SEP 9 2021.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 12/13032-5 - Geração e análise da imunogenicidade de proteínas recombinantes baseadas nas diferentes formas alélicas do antígeno circumsporozoíta de Plasmodium vivax visando o desenvolvimento de uma vacina universal contra malária
• Beneficiário: Irene da Silva Soares
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/26123-0 - Análise da imunidade protetora de formulações vacinais contra Plasmodium vivax após desafio com parasitos trangênicos P. berghei / P. vivax em modelo murino
• Beneficiário: Alba Marina Gimenez
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 14/18102-7 - Testes pré-clínicos de formulações vacinais baseadas em proteínas e adenovírus recombinantes expressando a proteína do circumsporozoíta de Plasmodium vivax
• Beneficiário: Alba Marina Gimenez
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado