A live, attenuated recombinant West Nile virus vaccine

Monath, Thomas P.; Liu, Jian; Kanesa-thasan, Niranjan; Myers, Gene; Nichols, Richard A.; Deary, Alison; McCarthy, Karen; Johnson, Casey; Ermak, Thomas H.; Shin, Sunheang; Arroyo, Juan; Guirakhoo, Farshad; Kennedy, Jennifer; Ennis, Francis A.; Green, Sharone; Bedford, Philip

doi:10.1073/pnas.0601932103

Cited by 208 publications

(131 citation statements)

References 31 publications

(29 reference statements)

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“…Recent clinical studies have indicated that antigenic chimeric flaviviruses are attenuated and immunogenic in human volunteers and may serve as live attenuated virus vaccines for protection against disease caused by DEN, JE, WN, and TBE viruses [27][28][29][30][31]. These positive results observed in several clinical trials support the further development and study of antigenic chimeric flaviviruses.…”

Section: Discussionmentioning

confidence: 87%

Evaluation of St. Louis encephalitis virus/dengue virus type 4 antigenic chimeric viruses in mice and rhesus monkeys

Blaney

Speicher

Hanson

et al. 2008

Vaccine

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SummaryTo develop a live attenuated virus vaccine against St. Louis encephalitis virus (SLE), two antigenic chimeric viruses were generated by replacing the membrane precursor and envelope protein genes of dengue virus type 4 (DEN4) with those from SLE with or without a 30 nucleotide deletion in the DEN4 3′ untranslated region of the chimeric genome. Chimeric viruses were compared with parental wild-type SLE for level of neurovirulence and neuroinvasiveness in mice and for safety, immunogenicity, and protective efficacy in rhesus monkeys. The resulting viruses, SLE/DEN4 and SLE/DEN4Δ30, had greatly reduced neuroinvasiveness in immunodeficient mice but retained neurovirulence in suckling mice. Chimerization of SLE with DEN4 resulted in only moderate restriction in replication in rhesus monkeys, whereas the presence of the Δ30 mutation led to overattenuation. Introduction of previously described attenuating paired charge-to-alanine mutations in the DEN4 NS5 protein of SLE/DEN4 reduced neurovirulence in mice and replication in rhesus monkeys. Two modified SLE/DEN4 viruses, SLE/DEN4-436,437 clone 41 and SLE/DEN4-654,655 clone 46, have significantly reduced neurovirulence in mice and conferred protective immunity in monkeys against SLE challenge. These viruses may be considered for use as SLE vaccine candidates and for use as diagnostic reagents with reduced virulence.

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Section: Discussionmentioning

confidence: 87%

Evaluation of St. Louis encephalitis virus/dengue virus type 4 antigenic chimeric viruses in mice and rhesus monkeys

Blaney

Speicher

Hanson

et al. 2008

Vaccine

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“…An effective dose is determined by several parameters, including how efficiently a vaccine virus replicates in infected cells in vivo in a given model. For instance, the live ChimeriVax-WN vaccine was more immunogenic in humans than in mice and monkeys (27,28). Based on recent epidemiological data for WN virus in North America, the WN backbone of RV-WN/TBE should enable efficient (single-cycle) replication in humans, and therefore an appropriate immunizing dose will need to be determined in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Single-dose vaccine against tick-borne encephalitis

Rumyantsev¹,

Goncalvez²,

Giel–Moloney³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Tick-borne encephalitis (TBE) virus is the most important human pathogen transmitted by ticks in Eurasia. Inactivated vaccines are available but require multiple doses and frequent boosters to induce and maintain immunity. Thus far, the goal of developing a safe, live attenuated vaccine effective after a single dose has remained elusive. Here we used a replication-defective (single-cycle) flavivirus platform, RepliVax, to generate a safe, single-dose TBE vaccine. Several RepliVax-TBE candidates attenuated by a deletion in the capsid gene were constructed using different flavivirus backbones containing the envelope genes of TBE virus. RepliVax-TBE based on a West Nile virus backbone (RV-WN/TBE) grew more efficiently in helper cells than candidates based on Langat E5, TBE, and yellow fever 17D backbones, and was found to be highly immunogenic and efficacious in mice. Live chimeric yellow fever 17D/TBE, Dengue 2/TBE, and Langat E5/TBE candidates were also constructed but were found to be underattenuated. RV-WN/TBE was demonstrated to be highly immunogenic in Rhesus macaques after a single dose, inducing a significantly more durable humoral immune response compared with three doses of a licensed, adjuvanted human inactivated vaccine. Its immunogenicity was not significantly affected by preexisting immunity against WN. Immunized monkeys were protected from a stringent surrogate challenge. These results support the identification of a single-cycle TBE vaccine with a superior product profile to existing inactivated vaccines, which could lead to improved vaccine coverage and control of the disease.flavivirus vaccine | prophylaxis | preclinical | nonhuman primate

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“…Attenuation of YFV-17D has been attributed to mutations in the YFV-17D envelope protein, which may hinder spread of the virus to visceral tissues, and was recently linked to reduced quasispecies diversity (Beck et al, 2014;Hahn et al, 1987;Lee & Lobigs, 2008). Considering that YFV-17D is currently being used in chimeric vaccines to JEV, and for the development of vaccines to WNV and DENV, a better understanding of its attenuation is imperative (Guirakhoo et al, 2006;Guy et al, 2010;Monath et al, , 2006Pugachev et al, 2005).…”

Section: Introductionmentioning

confidence: 99%