Construction and characterization of a second-generation pseudoinfectious West Nile virus vaccine propagated using a new cultivation system

Widman, Douglas G.; Ishikawa, Takahiro; Fayzulin, Rafik; Bourne, Nigel; Mason, Peter W.

doi:10.1016/j.vaccine.2008.03.009

Cited by 61 publications

(97 citation statements)

References 46 publications

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“…To enumerate the concentration of virus, we modified a protocol described previously (52). Briefly, Vero cells were inoculated with 50 l of sequential 10-fold dilutions of infectious supernatants.…”

Section: Methodsmentioning

confidence: 99%

Spleen Tyrosine Kinase (Syk) Mediates IL-1β Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection

Callaway

Smith

McKinnon

et al. 2015

Journal of Biological Chemistry

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Background: Insights into the mechanisms of elevated cytokine production during severe dengue disease are needed. Results: Dengue virus immune complexes induce inflammatory cytokine expression by activating spleen tyrosine kinase (Syk) during antibody-dependent enhancement of infection. Conclusion: Syk-mediated activation of ERK1/2 elevates cytokine production during antibody-enhanced dengue infection. Significance: Targeting Syk and ERK1/2 has therapeutic potential during antibody-enhanced dengue infection.

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Section: Methodsmentioning

confidence: 99%

Spleen Tyrosine Kinase (Syk) Mediates IL-1β Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection

Callaway

Smith

McKinnon

et al. 2015

Journal of Biological Chemistry

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“…Vero cells were maintained at 37°C in MEM containing 6% FBS and antibiotics. BHK(VEErep/C*-E/Pac) packaging cells expressing the WNV CprM-E proteins were propagated at 37°C in Dulbecco's MEM supplemented with 10% FBS and 10 g/ml puromycin as previously described (14,44). C7/10 mosquito cells were maintained at 30°C in Leibovitz's L15 medium supplemented with 10% FBS, 10% tryptose phosphate broth, and antibiotics.…”

Section: Methodsmentioning

confidence: 99%

“…A BAC-propagated cDNA derivative of our previously described single-cycle WNV lacking a functional C gene (28), designated RepliVAX WN.2, has been described (44). For the construction of the helper genome for our two-component genome system, we inserted a cassette consisting of the gene for the foot-and-mouth disease virus (FMDV)-2A autoproteinase and a codonoptimized WNV C gene between the truncated C and NS1 coding sequences in WNR-CNS1-5.…”

Section: Methodsmentioning

confidence: 99%

“…Identification of mutated CS that permitted the efficient replication of WNV genome encouraged us to examine their use in producing a two-component LAV based on our single-cycle WNV, named RepliVAX WN. The RepliVAX WN genome has a large deletion in the C-coding sequence so that it can be packaged only in C-expressing cell lines (28,44). Recently we reported that a C-expressing flavivirus replicon can also complement RepliVAX genomes (39).…”

Section: Vol 82 2008 Mutated Cs That Support Efficient Wnv Replicatmentioning

confidence: 99%

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Identification of Mutated Cyclization Sequences That Permit Efficient Replication of West Nile Virus Genomes: Use in Safer Propagation of a Novel Vaccine Candidate

Suzuki

Fayzulin²,

Frolov³

et al. 2008

J Virol

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“…By removing the ability of a virus to spread after initial infection, bona fide immune stimulation could be elicited without causing the pathogenesis that is associated with nascent virus production. This method has been used for developing several single-cycle replicating viruses, such as herpes simplex virus, simian immunodeficiency virus, West Nile virus, rabies virus, lymphocytic choriomeningitis virus, and murine cytomegalovirus (11)(12)(13)(14)(15)(16). One advantage of the single-cycle replicating virus is that it can trigger effective CD8 T cell responses (14,16,17).…”

mentioning

confidence: 99%

Induction of CD8 T Cell Heterologous Protection by a Single Dose of Single-Cycle Infectious Influenza Virus

Guo

Baker

Martínez-Sobrido

et al. 2014

J Virol

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The effector functions of specific CD8 T cells are crucial in mediating influenza heterologous protection. However, new approaches for influenza vaccines that can trigger effective CD8 T cell responses have not been extensively explored. We report here the generation of single-cycle infectious influenza virus that lacks a functional hemagglutinin (HA) gene on an X31 genetic background and demonstrate its potential for triggering protective CD8 T cell immunity against heterologous influenza virus challenge. In vitro, X31-sciIV can infect MDCK cells, but infectious virions are not produced unless HA is transcomplemented. In vivo, intranasal immunization with X31-sciIV does not cause any clinical symptoms in mice but generates influenza-specific CD8 T cells in lymphoid (mediastinal lymph nodes and spleen) and nonlymphoid tissues, including lung and bronchoalveolar lavage fluid, as measured by H2-Db NP366 and PA224 tetramer staining. In addition, a significant proportion of X31-sciIV-induced antigen-specific respiratory CD8 T cells expressed VLA-1, a marker that is associated with heterologous influenza protection. Further, these influenza-specific CD8 T cells produce antiviral cytokines when stimulated with NP366 and PA224 peptides, indicating that CD8 T cells triggered by X31-sciIV are functional. When challenged with a lethal dose of heterologous PR8 virus, X31-sciIV-primed mice were fully protected from death. However, when CD8 T cells were depleted after priming or before priming, mice could not effectively control virus replication or survive the lethal challenge, indicating that X31-sciIV-induced memory CD8 T cells mediate the heterologous protection. Thus, our results demonstrate the potential for sciIV as a CD8 T cell-inducing vaccine. IMPORTANCEOne of the challenges for influenza prevention is the existence of multiple influenza virus subtypes and variants and the fact that new strains can emerge yearly. Numerous studies have indicated that the effector functions of specific CD8 T cells are crucial in mediating influenza heterologous protection. However, influenza vaccines that can trigger effective CD8 T cell responses for heterologous protection have not been developed. We report here the generation of an X31 (H3N2) virus-derived single-cycle infectious influenza virus, X31-sciIV. A one-dose immunization with X31-sciIV is capable of inducing functional influenza virusspecific CD8 T cells that can be recruited into respiratory tissues and provide protection against lethal heterologous challenge. Without these cells, protection against lethal challenge was essentially lost. Our data indicate that an influenza vaccine that primarily relies on CD8 T cells for protection could be developed.

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Construction and characterization of a second-generation pseudoinfectious West Nile virus vaccine propagated using a new cultivation system

Cited by 61 publications

References 46 publications

Spleen Tyrosine Kinase (Syk) Mediates IL-1β Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection

Spleen Tyrosine Kinase (Syk) Mediates IL-1β Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection

Identification of Mutated Cyclization Sequences That Permit Efficient Replication of West Nile Virus Genomes: Use in Safer Propagation of a Novel Vaccine Candidate

Induction of CD8 T Cell Heterologous Protection by a Single Dose of Single-Cycle Infectious Influenza Virus

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