Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus.

Two molecularly engineered, live-attenuated West Nile virus (WN) vaccine candidates were highly attenuated and protective in rhesus monkeys. The vaccine candidates are chimeric viruses (designated WN/DEN4) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue 4 virus (DEN4) with or without a deletion of 30 nucleotides (Delta 30) in the 3' noncoding region of DEN4. Viremia in WN/DEN4- infected monkeys was reduced 100-fold compared to that in WN- or DEN4-infected monkeys. WN/DEN4-3'Delta 30 did not cause detectable viremia, indicating that it is even more attenuated for monkeys. These findings indicate that chimerization itself and the presence of the Delta 30 mutation independently contribute to the attenuation phenotype for nonhuman primates. Despite their high level of attenuation in monkeys, the chimeras induced a moderate-to-high titer of neutralizing antibodies and prevented viremia in monkeys challenged with WN. The more attenuated vaccine candidate, WN/DEN4-3'Delta 30, will be evaluated first in our initial clinical studies.

• Publication year

  2003

• Venue

  Virology

• Publication date

  2003-09-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/S0042-6822(03)00450-1PMID 14517072
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A Live, Attenuated Dengue Virus Type 1 Vaccine Candidate with a 30-Nucleotide Deletion in the 3′ Untranslated Region Is Highly Attenuated and Immunogenic in Monkeys

  2003cited by this paper
• B Cells and Antibody Play Critical Roles in the Immediate Defense of Disseminated Infection by West Nile Encephalitis Virus

  2003cited by this paper
• West Nile virus/dengue type 4 virus chimeras that are reduced in neurovirulence and peripheral virulence without loss of immunogenicity or protective efficacy

  2002influential reference
• Provisional surveillance summary of the West Nile virus epidemic--United States, January-November 2002.

  2002cited by this paper
• West Nile Virus

  2002cited by this paper
• Genetic basis of attenuation of dengue virus type 4 small plaque mutants with restricted replication in suckling mice and in SCID mice transplanted with human liver cells.

  2002cited by this paper
• Provisional surveillance summary of the West Nile virus epidemic--United States, January-November 2002.

  2002cited by this paper
• Paired Charge-to-Alanine Mutagenesis of Dengue Virus Type 4 NS5 Generates Mutants with Temperature-Sensitive, Host Range, and Mouse Attenuation Phenotypes

  2002influential reference
• Chemical Mutagenesis of Dengue Virus Type 4 Yields Mutant Viruses Which Are Temperature Sensitive in Vero Cells or Human Liver Cells and Attenuated in Mice

  2001cited by this paper
• Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3'-untranslated region.

  2001influential reference
• Prospects for Development of a Vaccine against the West Nile Virus

  2001influential reference
• Yellow fever vector live-virus vaccines: West Nile virus vaccine development

  2001cited by this paper
• Tick-Borne Langat/Mosquito-Borne Dengue Flavivirus Chimera, a Candidate Live Attenuated Vaccine for Protection against Disease Caused by Members of the Tick-Borne Encephalitis Virus Complex: Evaluation in Rhesus Monkeys and in Mosquitoes

  2001influential reference
• A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission from vaccinees to mosquitoes.

  2001influential reference
• Chimeric Langat/Dengue viruses protect mice from heterologous challenge with the highly virulent strains of tick-borne encephalitis virus.

  2000influential reference
• Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States.

  1999cited by this paper
• Attenuation of the Langat tick-borne flavivirus by chimerization with mosquito-borne flavivirus dengue type 4.

  1998influential reference
• Monkeys immunized with intertypic chimeric dengue viruses are protected against wild-type virus challenge

  1996cited by this paper
• Chimeric tick-borne encephalitis and dengue type 4 viruses: effects of mutations on neurovirulence in mice

  1993cited by this paper
• Construction and characterization of chimeric tick-borne encephalitis/dengue type 4 viruses.

  1992influential reference
• West Nile fever.

  1989cited by this paper
• Genetic factors associated with loss of the temperature-sensitive phenotype of the influenza A/Alaska/77-ts-1A2 recombinant during growth in vivo.

  1981cited by this paper
• Treatment of carcinoma of the rectosigmoid region.

  1947cited by this paper

• West Nile Virus: Epidemiology, Surveillance, and Prophylaxis with a Comparative Insight from Italy and Iran

  2026cites this paper
• Subgenomic flavivirus RNA as key target for live-attenuated vaccine development

  2024cites this paper
• A chimeric classical insect-specific flavivirus provides complete protection against West Nile virus lethal challenge in mice.

  2023cites this paper
• A Perspective on Current Flavivirus Vaccine Development: A Brief Review

  2023cites this paper
• Chimeric Vaccines Based on Novel Insect-Specific Flaviviruses

  2021cites this paper
• Current Progress of Avian Vaccines Against West Nile Virus

  2019cites this paper
• West Nile virus: an overview of current information

  2019cites this paper
• West Nile Encephalitis

  2018cites this paper
• A Live Attenuated Chimeric West Nile Virus Vaccine, rWN/DEN4&Dgr;30, Is Well Tolerated and Immunogenic in Flavivirus-Naive Older Adult Volunteers

  2017cites this paper
• West Nile Virus

  2016cites this paper
• West Nile Virus Infection

  2016cites this paper
• Batı Nil Virüs Enfeksiyonu

  2016cites this paper
• An Overview of Current Approaches Toward the Treatment and Prevention of West Nile Virus Infection

  2016cites this paper
• A Novel Synthetic TLR-4 Agonist Adjuvant Increases the Protective Response to a Clinical-Stage West Nile Virus Vaccine Antigen in Multiple Formulations

  2016cites this paper
• In vitro and in vivo characterization of chimeric duck Tembusu virus based on Japanese encephalitis live vaccine strain SA14-14-2.

  2016cites this paper
• Pathogenesis of West Nile Virus in Humans

  2015cites this paper
• Cloning and Expression of the E Protein from West

  2014cites this paper
• Experimental Infection of Rhesus Macaques and Common Marmosets with a European Strain of West Nile Virus

  2014cites this paper
• Current trends in West Nile virus vaccine development

  2014influential citation
• Assurance of neuroattenuation of a live vaccine against West Nile virus: a comprehensive study of neuropathogenesis after infection with chimeric WN/DEN4Δ30 vaccine in comparison to two parental viruses and a surrogate flavivirus reference vaccine.

  2014cites this paper
• West Nile Virus (Flaviviridae)

  2014cites this paper
• Cloning and Expression of the E Protein from West Nile Virus

  2014cites this paper
• Viral Infections of the Human Nervous System

  2013cites this paper
• Animal Models of Human Viral Diseases

  2013cites this paper
• The live attenuated chimeric vaccine rWN/DEN4Δ30 is well-tolerated and immunogenic in healthy flavivirus-naïve adult volunteers.

  2013cites this paper
• Development of chimaeric West Nile virus attenuated vaccine candidate based on the Japanese encephalitis vaccine strain SA14-14-2.

  2013cites this paper
• West Nile Fever

  2013cites this paper
• A Review of Vaccine Approaches for West Nile Virus

  2013cites this paper
• Immunization of West Nile recombinant envelope Domain III with equine CD40 ligand protein vaccine induced specific immune response in rabbits and horses

  2012cites this paper
• Phase II, dose ranging study of the safety and immunogenicity of single dose West Nile vaccine in healthy adults ≥ 50 years of age.

  2012cites this paper
• Research advances in plant-made flavivirus antigens.

  2012cites this paper
• 1 Encephalitic Flaviviruses

  2012cites this paper
• Towards a West Nile Virus Vaccine

  2012cites this paper
• Nucleic Acid-Based Infectious and Pseudo-Infectious Flavivirus Vaccines

  2011cites this paper
• Vaccines and immunotherapeutics for the prevention and treatment of infections with West Nile virus.

  2011cites this paper
• Phase II, randomized, double-blind, placebo-controlled, multicenter study to investigate the immunogenicity and safety of a West Nile virus vaccine in healthy adults.

  2011cites this paper
• Recombinant, Chimeric, Live, Attenuated Vaccines Against Flaviviruses and Alphaviruses

  2011cites this paper
• Characterization of the markers of blood-brain barrier disruption in West Nile virus infected mice

  2011influential citation
• Microarray hybridization for assessment of the genetic stability of chimeric west nile/dengue 4 virus

  2011cites this paper
• Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice

  2010cites this paper
• West Nile virus.

  2010cites this paper
• The development of flavivirus vaccines

  2010cites this paper
• Flavivirus Encephalitis

  2010cites this paper
• Evaluation of RepliVAX WN, a single-cycle flavivirus vaccine, in a non-human primate model of West Nile virus infection.

  2010cites this paper
• A recombinant West Nile virus envelope protein vaccine candidate produced in Spodoptera frugiperda expresSF+ cells.

  2009cites this paper
• Vaccine Development Against West Nile Virus

  2009cites this paper
• LABORATORY PRIMATE NEWSLETTER

  2009cites this paper
• Construction and characterization of a second-generation pseudoinfectious West Nile virus vaccine propagated using a new cultivation system.

  2008cites this paper
• Virus chimériques antigéniques de type 4 de l'encéphalite de saint-louis (sle)/la dengue

  2008cites this paper
• West Nile virus in the Americas.

  2008cites this paper
• Research and Development of Chimeric Flavivirus Vaccines

  2008cites this paper
• Third-generation flavivirus vaccines based on single-cycle, encapsidation-defective viruses.

  2008cites this paper
• Identification of Mutated Cyclization Sequences That Permit Efficient Replication of West Nile Virus Genomes: Use in Safer Propagation of a Novel Vaccine Candidate

  2008cites this paper
• Evaluation of St. Louis encephalitis virus/dengue virus type 4 antigenic chimeric viruses in mice and rhesus monkeys.

  2008cites this paper
• [West Nile Virus infection in perinatology].

  2007cites this paper
• Induction of Epitope-Specific Neutralizing Antibodies against West Nile Virus

  2007cites this paper
• Induction of Epitope-Specific Neutralizing Antibodies against

  2007cites this paper
• West Nile virus: recent trends in diagnosis and vaccine development.

  2007cites this paper
• West Nile virus: epidemiology and clinical features of an emerging epidemic in the United States.

  2006cites this paper
• rDEN2/4Δ30(ME), a Live Attenuated Chimeric Dengue Serotype 2 Vaccine, is Safe and Highly Immunogenic in Healthy Dengue-Naïve Adults

  2006cites this paper
• Clinical manifestations , diagnosis , and treatment of West Nile virus infection

  2006cites this paper
• Non-structural proteins of dengue 2 virus offer limited protection to interferon-deficient mice after dengue 2 virus challenge.

  2006cites this paper
• Monoclonal Antibody-Based Competitive Enzyme-Linked Immunosorbent Assay for Detecting and Quantifying West Nile Virus-Neutralizing Antibodies in Horse Sera

  2006cites this paper
• West Nile virus meningoencephalitis

  2006cites this paper
• Comparison of live and inactivated tick-borne encephalitis virus vaccines for safety, immunogenicity and efficacy in rhesus monkeys.

  2006cites this paper
• Baboon model for West Nile virus infection and vaccine evaluation.

  2006cites this paper
• Chimeric West Nile/dengue virus vaccine candidate: preclinical evaluation in mice, geese and monkeys for safety and immunogenicity.

  2006influential citation
• West Nile virus neuroinvasive disease

  2006cites this paper
• 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

  2006cites this paper
• Determining genetic stabilities of chimeric dengue vaccine candidates based on dengue 2 PDK-53 virus by sequencing and quantitative TaqMAMA.

  2006cites this paper
• Immunoglobulins and Immunoglobulin Fc Receptors in Nonhuman Primates Commonly Used in Biomedical Research

  2006cites this paper
• rDEN4Δ30, a Live Attenuated Dengue Virus Type 4 Vaccine Candidate, Is Safe, Immunogenic, and Highly Infectious in Healthy Adult Volunteers

  2005cites this paper
• New developments in flavivirus vaccines with special attention to yellow fever

  2005cites this paper
• Infectivity of West Nile/Dengue Chimeric Viruses for West Nile and Dengue Mosquito Vectors

  2005cites this paper
• rDEN4delta30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers.

  2005cites this paper
• West Nile premembrane-envelope genetic vaccine encoded as a chimera containing the transmembrane and cytoplasmic domains of a lysosome-associated membrane protein: increased cellular concentration of the transgene product, targeting to the MHC II compartment, and enhanced neutralizing antibody respo

  2005cites this paper
• A recombinant envelope protein vaccine against West Nile virus.

  2005cites this paper
• Live measles vaccine expressing the secreted form of the West Nile virus envelope glycoprotein protects against West Nile virus encephalitis.

  2005cites this paper
• Chemiluminescent optical fiber immunosensor for the detection of anti-West Nile virus IgG.

  2005cites this paper
• The suitability of yellow fever and Japanese encephalitis vaccines for immunization against West Nile virus.

  2005cites this paper
• Chimeric Dengue 2 PDK-53/West Nile NY99 Viruses Retain the Phenotypic Attenuation Markers of the Candidate PDK-53 Vaccine Virus and Protect Mice against Lethal Challenge with West Nile Virus

  2005cites this paper
• West Nile Virus Infection of the Nervous System

  2005cites this paper
• Risk assessment on severe hazards to China caused by West Nile virus

  2004cites this paper
• West Nile virus infection: a pediatric perspective.

  2004cites this paper
• The West Nile Virus: A Lesson in Emerging Infections

  2004cites this paper
• West Nile virus: a growing concern?

  2004cites this paper
• ChimeriVax-West Nile Virus Live-Attenuated Vaccine: Preclinical Evaluation of Safety, Immunogenicity, and Efficacy

  2004cites this paper
• West Nile virus vaccines

  2004cites this paper
• Live flavivirus vaccines: reasons for caution.

  2004cites this paper
• Desarrollo de vacunas frente a las infecciones por dengue

  2004cites this paper
• West Nile virus infection in the United States.

  2004cites this paper
• Recent advancement in flavivirus vaccine development

  2004cites this paper
• Genetically modified, live attenuated dengue virus type 3 vaccine candidates.

  2004cites this paper
• A review of licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines

  2004cites this paper
• West Nile virus: where are we now?

  2004cites this paper
• A young man with rectal polyps

  2004cites this paper
• Unhappy neighbourhood: spatial genome organisation and lymphomagenesis in B cells.

  2003cites this paper
• The West Nile season.

  2003cites this paper
• CHIMERIC SLE / DENGUE TYPE 4 ANTIGENIC VIRUSES Sequence

  year unknowncites this paper