2016, Number 2
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Biotecnol Apl 2016; 33 (2)
A new tetravalent Dengue vaccine formulation based on four chimeric envelope domain III-capsid proteins induces a functional immune response in mice and non-human primates
Suzarte E, Gil L, Hermida L, Marcos E, Valdés I, Lazo L, Guillén G, Álvarez M, Izquierdo A, Guzmán MG, Pérez Y, García A, Silva JA, Castro J, Brown E, Hernández A, Rodríguez Y, López L, Ramos Y, Falcón V, Ramírez R, Romero Y, Blanco A, Ortega O, Mendez A, Cobas K, González S, Vazquez M
Language: English
References: 12
Page: 2511-2514
PDF size: 228.12 Kb.
ABSTRACT
It is crucial in dengue a tetravalent vaccine candidate effective against the four dengue virus (DENV) serotypes, considering the lack of long lasting cross-protective immunity among infections with either serotype, and the fact that secondary heterotypic infections can led to severe forms of the disease. In this work, it was described for the first time the generation and characterization of the protein chimeric variants domain III-capsid (DIIIC) of DENV serotypes 1, 3 and 4, based on previous evidences of the ability of DIIIC-2 protein aggregated with oligodeoxynucleotide (ODN) 39M to induce a protective immunity in mice and monkeys. The recombinant proteins DIIIC-1, 3 and 4 aggregated with the ODN 39M, independently or combined with DIIIC-2 in a tetravalent formulation were evaluated in mice, demonstrating the induction of a humoral and cellular immune response able to protect against the four viral serotypes. The tetravalent DIIIC formulation was further evaluated in monkeys administered through different routes, demonstrating the induction of functional humoral and cell immune responses, results that opens the doors to clinical trials to this new tetravalent formulation against dengue. This research granted the 2015 Award of the Cuban National Academy of Sciences.
REFERENCES
Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504-7.
Sabchareon A, Wallace D, Sirivichayakul C, Limkittikul K, Chanthavanich P, Suvannadabba S, et al. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet. 2012;380(9853):1559-67.
Capeding MR, Tran NH, Hadinegoro SR, Ismail HI, Chotpitayasunondh T, Chua MN, et al. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. Lancet. 2014;384(9951):1358-65.
Villar L, Dayan GH, Arredondo-Garcia JL, Rivera DM, Cunha R, Deseda C, et al. Efficacy of a tetravalent dengue vaccine in children in Latin America. N Engl J Med. 2015;372(2):113-23.
Gil L, Lopez C, Lazo L, Valdes I, Marcos E, Alonso R, et al. Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice. Int Immunol. 2009;21(10):1175-83.
Gil L, Izquierdo A, Lazo L, Valdes I, Ambala P, Ochola L, et al. Capsid protein: evidences about the partial protective role of neutralizing antibody-independent immunity against dengue in monkeys. Virology 2014;456-457:70-6.
Gil L, Marcos E, Izquierdo A, Lazo L, Valdes I, Ambala P, et al. The protein DIIIC-2, aggregated with a specific oligodeoxynucleotide and adjuvanted in alum, protects mice and monkeys against DENV- 2. Immunol Cell Biol. 2015;93(1):57-66.
Suzarte E, Marcos E, Gil L, Valdes I, Lazo L, Ramos Y, et al. Generation and characterization of potential dengue vaccine candidates based on domain III of the envelope protein and the capsid protein of the four serotypes of dengue virus. Arch Virol. 2014;159(7):1629-40.
Simmons M, Murphy GS, Hayes CG. Short report: Antibody responses of mice immunized with a tetravalent dengue recombinant protein subunit vaccine. Am J Trop Med Hyg. 2001;65(2):159-61.
Konishi E, Kosugi S, Imoto J. Dengue tetravalent DNA vaccine inducing neutralizing antibody and anamnestic responses to four serotypes in mice. Vaccine. 2006;24(12):2200-7.
Clements DE, Coller BA, Lieberman MM, Ogata S, Wang G, Harada KE, et al. Development of a recombinant tetravalent dengue virus vaccine: immunogenicity and efficacy studies in mice and monkeys. Vaccine. 2010;28(15):2705-15.
Suzarte E, Gil L, Valdes I, Marcos E, Lazo L, Izquierdo A, et al. A novel tetravalent formulation combining the four aggregated domain III-capsid proteins from dengue viruses induces a functional immune response in mice and monkeys. Int Immunol. 2015;27(8):367-79.