A single immunization with a minute dose of a lentiviral vector-based vaccine is highly effective at eliciting protective humoral immunity against West Nile virus

Maria Candela Iglesias; Marie-Pascale Frenkiel; Karine Mollier; Philippe Souque; Philippe Despres; Pierre Charneau

doi:10.1002/jgm.837

A single immunization with a minute dose of a lentiviral vector-based vaccine is highly effective at eliciting protective humoral immunity against West Nile virus

The Journal of Gene Medicine ◽

10.1002/jgm.837 ◽

2006 ◽

Vol 8 (3) ◽

pp. 265-274 ◽

Cited By ~ 54

Author(s):

Maria Candela Iglesias ◽

Marie-Pascale Frenkiel ◽

Karine Mollier ◽

Philippe Souque ◽

Philippe Despres ◽

...

Keyword(s):

West Nile Virus ◽

Humoral Immunity ◽

Lentiviral Vector ◽

West Nile ◽

Highly Effective ◽

Minute Dose

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Viral RNA-Dependent RNA Polymerase Inhibitor 7-Deaza-2′-C-Methyladenosine Prevents Death in a Mouse Model of West Nile Virus Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02093-18 ◽

2019 ◽

Vol 63 (3) ◽

Cited By ~ 6

Author(s):

Luděk Eyer ◽

Martina Fojtíková ◽

Radim Nencka ◽

Ivo Rudolf ◽

Zdeněk Hubálek ◽

...

Keyword(s):

West Nile Virus ◽

West Nile Virus Infection ◽

Antiviral Effect ◽

Vero Cells ◽

Modified Nucleosides ◽

West Nile ◽

Brain Infection ◽

Highly Effective ◽

Time Of Infection

ABSTRACTWest Nile virus (WNV) is a medically important emerging arbovirus causing serious neuroinfections in humans and against which no approved antiviral therapy is currently available. In this study, we demonstrate that 2′-C-methyl- or 4′-azido-modified nucleosides are highly effective inhibitors of WNV replication, showing nanomolar or low micromolar anti-WNV activity and negligible cytotoxicity in cell culture. One representative ofC2′-methylated nucleosides, 7-deaza-2′-C-methyladenosine, significantly protected WNV-infected mice from disease progression and mortality. Twice daily treatment at 25 mg/kg starting at the time of infection resulted in 100% survival of the mice. This compound was highly effective, even if the treatment was initiated 3 days postinfection, at the time of a peak of viremia, which resulted in a 90% survival rate. However, the antiviral effect of 7-deaza-2′-C-methyladenosine was absent or negligible when the treatment was started 8 days postinfection (i.e., at the time of extensive brain infection). The 4′-azido moiety appears to be another important determinant for highly efficient inhibition of WNV replicationin vitro. However, the strong anti-WNV effect of 4′-azidocytidine and 4′-azido-aracytidine was cell type dependent and observed predominantly in porcine kidney stable (PS) cells. The effect was much less pronounced in Vero cells. Our results indicate that 2′-C-methylated or 4′-azidated nucleosides merit further investigation as potential therapeutic agents for treating WNV infections as well as infections caused by other medically important flaviviruses.

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Viral RNA-dependent RNA polymerase inhibitor 7-deaza-2′-C-methyladenosine prevents death in a mouse model of West Nile virus infection

10.1101/432955 ◽

2018 ◽

Author(s):

Luděk Eyer ◽

Martina Fojtíková ◽

Radim Nencka ◽

Ivo Rudolf ◽

Zdeněk Hubálek ◽

...

Keyword(s):

West Nile Virus ◽

Post Infection ◽

West Nile Virus Infection ◽

Antiviral Effect ◽

Vero Cells ◽

Modified Nucleosides ◽

West Nile ◽

Brain Infection ◽

Highly Effective

AbstractWest Nile virus (WNV) is a medically important emerging arbovirus causing serious neuroinfections in humans against which no approved antiviral therapy is currently available. In this study, we demonstrate that 2′-C- methyl- or 4′-azido-modified nucleosides are highly effective inhibitors of WNV replication, showing nanomolar or low micromolar anti-WNV activity and negligible cytotoxicity in cell culture. One representative ofC2′-methylated nucleosides, 7-deaza-2′-C- methyladenosine, significantly protected WNV-infected mice from disease progression and mortality. Twice daily treatment at 25 mg/kg starting at the time of infection resulted in 100% survival of the mice. This compound was highly effective, even if the treatment was initiated 3 days post-infection, at the time of a peak of viremia, which resulted in a 90% survival rate. However, the antiviral effect of 7-deaza-2′-C- methyladenosine was absent or negligible when the treatment was started 8 days post-infection (i.e., at the time of extensive brain infection). The 4′-azido moiety appears to be another important determinant for highly efficient inhibition of WNV replication in vitro. However, the strong anti-WNV effect of 4′-azidocytidine and 4′-azido-aracytidine was cell type-dependent and observed predominantly in PS cells. The effect was much less pronounced in Vero cells. Our results indicate that 2′-C- methylated or 4′-azidated nucleosides merit further investigation as potential therapeutic agents for treating WNV infections, as well as infections caused by other medically important flaviviruses.

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