Construction, characterization and immunogenicity of recombinant yellow fever 17D-dengue type 2 viruses

Caufour, Philippe; Motta, Mario; Yamamura, Anna Maya Yoshida; Vázquez, Susana; Ferreira, I.I; Jabor, A.V.; Bonaldo, Myrna C.; Freire, Marcos S.; Galler, Ricardo

doi:10.1016/s0168-1702(01)00273-8

Cited by 64 publications

(62 citation statements)

References 32 publications

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“…challenge the majority of pre-clinical development of vaccines is performed in young mice, no older than 6 weeks and neutralizing antibodies is correlated with protection. [21][22][23] Immunocompetent mice inoculated with wild type dengue virus (wtDENV) through i.p. or i.m.…”

Section: Discussionmentioning

confidence: 99%

“…22 Another CYD vaccine constructed with prM/E of DENV-2 NGC strain, developed by Caufour et al, 23 demonstrated that Swiss mice immunized with an IP dose of 10 5 PFU in a three dose schedule developed high titers of NAb (PRNT 50 D 1:426 to 1:4265) against homologous DENV-2 NCG, two weeks after the last dose and 85% the animals were protected against challenge with 220LD 50 . By the time of challenge, immunization with our recombinant VSV-DENV-2 induced NAb titers of PRNT 50 D 100 and protected 80% of the animals challenged with 50LD 50 of TR1751 DENV-2 strain.…”

Section: Discussionmentioning

confidence: 99%

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Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection

Lauretti

Chattopadhyay

França

et al. 2016

Human Vaccines & Immunotherapeutics

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Dengue is the most important arbovirus disease throughout the world and it is responsible for more than 500,000 dengue hemorrhagic cases and 22,000 deaths every year. One vaccine was recently licensed for human use in Brazil, Mexico and Philippines and although at least seven candidates have been in clinical trials the results of the most developed CYD vaccine have demonstrated immunization problems, such as uneven protection and interference between serotypes. We constructed a vaccine candidate based on vesicular stomatitis virus (VSV) expression of pre-membrane (prM) and envelope (E) proteins of dengue-2 virus (DENV-2) and tested it in mice to evaluate immunogenicity and protection against DENV-2 infection. VSV has been successfully used as vaccine vectors for several viruses to induce strong humoral and cellular immune responses. The VSV-DENV-2 recombinant was constructed by inserting the DENV-2 structural proteins into a VSV plasmid DNA for recombinant VSV-DENV-2 recovery. Infectious recombinant VSV viruses were plaque purified and prM and E expression were confirmed by immunofluorescence and radiolabeling of proteins of infected cells. Forty Balb/C mice were inoculated through subcutaneous (s.c.) route with VSV-DENV-2 vaccine in a two doses schedule 15 d apart and 29 d after first inoculation, sera were collected and the mice were challenged with 50 lethal doses (LD 50 ) of a neurovirulent DENV-2. The VSV-DENV-2 induced anti-DENV-2 antibodies and protected animals in the challenge experiment comparable to DENV-2 immunization control group. We conclude that VSV is a promising platform to test as a DENV vaccine and perhaps against others Flaviviridae.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection

Lauretti

Chattopadhyay

França

et al. 2016

Human Vaccines & Immunotherapeutics

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“…Protection against encephalitis or viremia reflects efficacy in the mouse and monkey models, respectively. In our efforts to develop a live attenuated dengue vaccine based on chimeric yellow fever 17D viruses (Caufour et al 2001, Mateu et al 2007) and in the unavailability of wild type dengue viruses well characterized for viremia in rhesus monkeys, we have aimed at establishing a nonhuman primate model to test the protective capability of the recombinant viruses.…”

Section: Discussionmentioning

confidence: 99%

“…Although some hallmarks of dengue severe syndromes have been described (Halstead et al 1973a,b), it is widely accepted that the main parameters to be considered are neutralizing antibodies induced by the vaccine candidate and the magnitude and duration of peripheral viremia upon challenge of previously immunized animals (Halstead & Marchette 2003, Raviprakash et al 2003, Hanley et al 2004, Guirakhoo et al 2004, Blaney et al 2005, Sun et al 2006). In our efforts to develop a live attenuated dengue vaccine based on chimeric VF 17D viruses (Caufour et al 2001, Mateu et al 2007 we needed to establish a nonhuman primate model to test the protective capability of the recombinant viruses. Here, we describe the infectivity of wild-type dengue types 1, 2, and 3 viruses to rhesus monkeys and discuss their use in testing the efficacy of dengue vaccines in general.…”

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confidence: 99%

<![CDATA[<B>Wild dengue virus types 1, 2 and 3 viremia in rhesus monkeys</B>]]>

Freire¹,

Marchevsky²,

Almeida³

et al. 2007

Mem. Inst. Oswaldo Cruz

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“…We selected a pathogenic strain of dengue virus (DENV) 2 (16681) originated from a DHF SE Asian case and the Brazilian YF17DD, which is known for its protective properties with minimal deleterious effects. A chimeric YF17D/DENV2 vaccine virus (Caufour et al 2001) was assayed as well. We report for the first time that flaviviruses induce the expression of the DC maturation marker CD38 and downregulate OX40L, suggesting that a Th-1 response has been generated.…”

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confidence: 99%

Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles

Gandini

Reis

Torrentes-Carvalho

et al. 2011

Mem. Inst. Oswaldo Cruz

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Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs) are targets for dengue virus (DENV) and yellow fever virus (YF) replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681), a YF vaccine (YF17DD) and a chimeric YF17D/DENV2 vaccine in monocytederived DCs in vitro with regard to cell maturation, activation and cytokine production. Higher viral antigen positive cell frequencies were observed for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures exhibited dendritic cell activation and maturation molecules. CD38 expression on DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was decreased as compared to mock-stimulated cells, suggesting that a T helper 1 profile is favoured. Tumor necrosis factor (TNF)-α production in cell cultures was significantly higher in DENV2-infected cultures than in cultures infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN-α levels than DENV2. The differential cytokine production indicates that DENV2 results in TNF induction, which discriminates it from vaccine viruses that preferentially stimulate interferon expression. These differential response profiles may influence the pathogenic infection outcome.Key words: cytokines -dendritic cells -dengue virus -yellow fever vaccine -flavivirus dendritic cell activation by flavivirus • Mariana Gandini et al.

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Construction, characterization and immunogenicity of recombinant yellow fever 17D-dengue type 2 viruses

Cited by 64 publications

References 32 publications

Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection

Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection

<![CDATA[<B>Wild dengue virus types 1, 2 and 3 viremia in rhesus monkeys</B>]]>

Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles

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