2018, Number 1
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Biotecnol Apl 2018; 35 (1)
Nucleocapsid-like particles, an alternative and safe vaccine strategy against Dengue virus based on the induction of cell-mediated alone adaptive immune responses
Gil L, Lazo L, Cobas K, Hermida L, Suzarte E, Marcos E, Izquierdo A, Valdés I, Guillén G, Guzman MG, Hernández L
Language: English
References: 16
Page: 1511-1514
PDF size: 411.40 Kb.
ABSTRACT
The development of an effective and safe vaccine against the Dengue virus has been limited by the absence of a
definite correlate of protection, together with the possibility of amplification of the viral infection by the neutralizing
antibody response of low affinity and concentration. However, the cellular immune response offers possibilities
to develop protection safely, and may be able to prevent the development of the severe form of the
disease. The present work focused on the capsid protein, which is the main target of the CD4+ T cell response,
and against which the CD8+ T cell response is generated during the natural infection in the absence of its recognition
by antibodies in the native virus. The capsid protein of serotype 2 was obtained recombinant and it was
observed that it formed nucleocapsid-like particles (NLPs-2) when incubated with oligodeoxynucleotides (ODN).
These NLPs-2 induced a functional and protective cellular immune response in BALB mice. Subsequently, proteins
were obtained for the remaining serotypes and their corresponding NLP. The tetravalent formulation of the
NLPs was evaluated immunologically in BALB mice and monkeys. It was possible to induce an immune response
mediated by IFN gamma-secreting cells after viral stimulus in vitro, in addition to controlling the viral load after
the challenge. This work received the Annual Award of the Cuban Academy of Sciences for the year 2017.
REFERENCES
Halstead SB, Suaya JA, Shepard DS. The burden of dengue infection. Lancet. 2007;369(9571):1410-1.
Halstead SB, Scanlon JE, Umpaivit P, Udomsakdi S. Dengue and chikungunya virus infection in man in Thailand, 1962- 1964. IV. Epidemiologic studies in the Bangkok metropolitan area. Am J Trop Med Hyg. 1969;18(6):997-1021.
Goncalvez AP, Engle RE, St Claire M, Purcell RH, Lai CJ. Monoclonal antibodymediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention. Proc Natl Acad Sci U S A. 2007;104(22):9422-7.
Yauch LE, Zellweger RM, Kotturi MF, Qutubuddin A, Sidney J, Peters B, et al. A protective role for dengue virus-specific CD8+ T cells. J Immunol. 2009;182(8):4865-73.
Yauch LE, Prestwood TR, May MM, Morar MM, Zellweger RM, Peters B, et al. CD4(+) T cells are not required for the induction of dengue virus-specific CD8(+) T cell or antibody responses but contribute to protection after vaccination. J Immunol. 2010;185(9):5405-16.
Zellweger RM, Miller R, Eddy WE, White LJ, Johnston RE, Shresta S. Role of humoral versus cellular responses induced by a protective dengue vaccine candidate. Plos Pathogens. 2013;9(10):e1003723.
Zellweger RM, Eddy WE, Tang WW, Miller R, Shresta S. CD8+ T cells prevent antigen-induced antibody-dependent enhancement of dengue disease in mice. J Immunol. 2014;193(8):4117-24.
Weiskopf D, Angelo MA, de Azeredo EL, Sidney J, Greenbaum JA, Fernando AN, et al. Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells. Proc Natl Acad Sci U S A. 2013;110(22):E2046-53.
Kuhn RJ, Zhang W, Rossmann MG, Pletnev SV, Corver J, Lenches E, et al. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell. 2002;108(5):717-25.
Mukhopadhyay S, Kuhn RJ, Rossmann MG. A structural perspective of the flavivirus life cycle. Nat Rev Microbiol. 2005;3(1):13-22.
Wengler G, Wengler G, Boege U, Wahn K. Establishment and analysis of a system which allows assembly and disassembly of alphavirus core-like particles under physiological conditions in vitro. Virology. 1984 Jan 30;132(2):401-12.
Gil L, Bernardo L, Pavon A, Izquierdo A, Valdes I, Lazo L, et al. Recombinant nucleocapsid-like particles from dengue-2 induce functional serotype-specific cellmediated immunity in mice. J Gen Virol. 2012;93:1204-14.
Lopez C, Gil L, Lazo L, Menendez I, Marcos E, Sanchez J, et al. In vitro assembly of nucleocapsid-like particles from purified recombinant capsid protein of dengue-2 virus. Arch Virol. 2009;154(4):695-8.
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.
Gil L, Cobas K, Lazo L, Marcos E, Hernandez L, Suzarte E, et al. A tetravalent formulation based on recombinant nucleocapsid-like particles from dengue viruses induces a functional immune response in mice and monkeys. J Immunol. 2016;197(9):3597-606.
Guzman MG, Alvarez M, Halstead SB. Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection. Arch Virol. 2013;158(7):1445-59.