But in retrospect, what it did was highlight the importance of travel and trade,” Petersen said in an interview. Vaccine was prepared under current good manufacturing practice conditions by Vical. The T cell immune response and neutralizing antibody elicited by this WNV DNA vaccine further suggests that needle-free immunization of DNA plasmids can reproducibly elicit significant cellular and humoral immune responses and merits further clinical investigation. Data were analyzed by curve fitting and nonlinear regression in order to describe the shape of the dose response and calculate an EC50. Subjects were followed for a total of 32 weeks, and the study was completed in July 2006. A live attenuated WNV vaccine based on chimeric flavivirus technology (ChimeriVax-West Nile; Acambis) has completed phase 1 and is currently in phase 2 trials [21]. The plasmid encodes for a single polypeptide encompassing a modified signal sequence from JEV fused upstream of the WNV prM and E coding sequences cloned into the expression vector VR-1012 (CMV backbone). Here, we use a selection protocol to identify a set of conserved prevalidated immunogenic T cell epitopes comprising a putative WNV vaccine.
West Nile virus (WNV) is a mosquitoborne flavivirus that can cause severe meningitis and encephalitis in infected individuals. Data are presented as the reciprocal dilution of serum corresponding to the EC50 and are adjusted to consider the final 300-µL volume of the neutralization reaction. 3 CD8+ T cell epitopes (ITYTDVLRY, TLARGFPFV, and SYHDRRWCF) and 1 CD4+ epitope (VTVNPFVSVATANAKVLI) were selected as a putative WNV vaccine, with an estimated PPC of 97.14%. A Review of Vaccine Approaches for West Nile Virus.
| The postvaccination titers 3 weeks after a single 1-mg dose of the WNV DNA vaccine in horses was similar to the titers elicited in humans in this clinical trial after 2 or 3 doses of vaccine (figure 2). Overall, our work provides a promising starting point for the exploration of next-generation WNV vaccines. The subject population was 67% male, with a mean age of 28.5 years. The principal form of transmission to humans is from the bite of an infected mosquito.
ChimeriVax-West Nile virus live-attenuated vaccine: preclinical evaluation of safety, immunogenicity, and efficacy. All CTL 9mer epitopes were entered into EPISOPT to estimate the PCC for the five US ethnic groups (see Table 1). 2013; 10(9):4200-4223. Antibody responses. While infection from other lineages is known, major human outbreaks arise solely from lineages 1, 2, and 5 [6]. Twelve of 15 subjects completed the vaccination schedule.
The virus has spread across North and Central America and into South America since its emergence in New York in 1999. Growth characteristics of the veterinary vaccine candidate ChimeriVax-West Nile (WN) virus in Aedes and Culex mosquitoes. In this review, the rationale for a human and veterinary vaccine is presented and a novel approach for rapid development of a molecularly-defined, live, attenuated vaccine is described. YTM9, SLF9, and KNM9 were eliminated as they lacked ≥50% sequence identity to the viral reference.
Even before West Nile was confirmed as the cause, the outbreak provoked an effective public health response. Variability across the genome is uneven, with the structural proteins being the least variable [29].
The ensemble identified is a viable starting point for further in vitro characterization or phase 0 trials, since we can assume that this epitope selection is likely both safe and immunogenic in the majority of most populations. Healio.com. All major human lineages were present; 5 sequences were generated with two representing lineage 2: AJW59217 (USA, 2002), AJR27898 (Italy, 2014), AHB37632 (Italy, 2013/08), AMZ00438 (India, 1988/02/12), and ALK02494 (Australia, 1991). Phylogenetic analysis suggests that there are at least seven distinct WNV lineages [8]. It took him 8 or 9 days to recover. Only visits after 24 November 2015 are recorded. To generate a truly universal vaccine, crossprotection against all WNV lineages and strains should be investigated. A Review of Vaccine Approaches for West Nile Virus. Data are shown for the entire study (weeks 0–32). Conclusions. This backbone encoding the CMV promoter and 5′ intron A was also used to construct a 4-plasmid HIV multiclade DNA vaccine previously shown to be safe and immunogenic in healthy adults [23]. ClinicalTrials.gov identifier: NCT00106769.
Oxford University Press is a department of the University of Oxford. Vaccine. The clinical trial will test the safety of the vaccine as well as its ability to produce an immune response.
Company: Merial West Nile Virus Vaccine, Live Canarypox Vector Description: Contents: RECOMBITEK ® Equine West Nile Virus contains a lyophilized recombinant canarypox vectored West Nile Virus vaccine plus a sterile liquid diluent. There are no licensed therapeutics against WNV, limiting effective infection control. Subjects G and H received 2 doses of vaccine. West Nile virus (WNV) is a vectorborne member of the Flavivirus genus, which includes several clinically and economically important human pathogens, such as yellow fever virus, 4 serotypes of dengue virus, and Japanese encephalitis virus (JEV). The city established a telephone hotline to answer questions and warned the public with leaflets and public messages on the radio and TV to take precautions against mosquitoes. Ann N Y Acad Sci. SAS (version 9.0; SAS Institute) and S-plus (version 6.2; Insightful) were used for analyses. “The fact that it showed up in a place like New York City makes perfect sense. 2014 Apr;108(3):148-57. doi: 10.1179/2047773214Y.0000000137. Subset of epitopes that represent all HLA-II alleles by elimination of repetitive binding profiles. Responding to her tip, investigators identified a local cluster of six more patients with similar symptoms, including five with “profound muscle weakness,” as their condition was later described in an MMWR report. None of the protective binding alleles suggested by Sarri et al. The equine DNA vaccine, pCBWN (Fort Dodge Animal Health in collaboration with the Centers for Disease Control and Prevention [CDC]), also encodes for the prM and E proteins from WNV and, in WNV challenge studies in both mice and horses, elicits neutralizing antibody and confers protection against viremia [19]. Background. Other approaches to vaccine development are briefly reviewed. For more information about NIH and its programs, visit www.nih.gov.
West Nile virus (a mosquito-borne flavivirus) has flourished in the North American ecosystem and is expected to expand its geographic range. The dose and route studied in this trial were based on clinical trials ofVRCDNAvaccines for other pathogens [23–25]. Layton said Asnis, who died in 2015, demonstrated how crucial it is for physicians to astutely report unusual findings to public health officials.
those of the individual authors and contributors and not of the publisher and the editor(s). According to Layton, the CDC’s finding was unexpected. Gray and C. E. Webb, “A review of the epidemiological and clinical aspects of West Nile virus,”, S. Ulbert and S. E. Magnusson, “Technologies for the development of West Nile virus vaccines,”, K. L. Tyler, “Current developments in understanding of West Nile virus central nervous system disease,”, M. C. Lanteri, J. W. Heitman, R. E. Owen et al., “Comprehensive analysis of West Nile virus-specific T cell responses in humans,”, A. V. Iyer and K. G. Kousoulas, “A review of vaccine approaches for West Nile virus,”, S. Brandler and F. Tangy, “Vaccines in development against West Nile virus,”, M. Molero-Abraham, E. M. Lafuente, D. R. Flower, and P. A. Reche, “Selection of conserved epitopes from hepatitis C virus for pan-populational stimulation of T-cell responses,”, Q. M. Sheikh, D. Gatherer, P. A. Reche, and D. R. Flower, “Towards the knowledge-based design of universal influenza epitope ensemble vaccines,”, S. A. Damfo, P. Reche, D. Gatherer, and D. R. Flower, “, J. Alonso-Padilla, E. M. Lafuente, and P. A. Reche, “Computer-aided design of an epitope-based vaccine against Epstein-Barr virus,”, J. Mistry and D. R. Flower, “Designing epitope ensemble vaccines against TB by selection: prioritizing antigens using predicted immunogenicity,”, P. Shah, J. Mistry, P. A. Reche, D. Gatherer, and D. R. Flower, “In silico design of mycobacterium tuberculosis epitope ensemble vaccines,”, D. Murphy, P. Reche, and D. R. Flower, “Selection-based design of in silico dengue epitope ensemble vaccines,”, M. Garcia-Boronat, C. M. Diez-Rivero, E. L. Reinherz, and P. A. Reche, “PVS: a web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery,”, J. Greenbaum, J. Sidney, J. Chung, C. Brander, B. Peters, and A. Sette, “Functional classification of class II human leukocyte antigen (HLA) molecules reveals seven different supertypes and a surprising degree of repertoire sharing across supertypes,”, V. Jaravine, S. Raffegerst, D. J. Schendel, and D. Frishman, “Assessment of cancer and virus antigens for cross-reactivity in human tissues,”, C. P. McMurtrey, A. Lelic, P. Piazza et al., “Epitope discovery in West Nile virus infection: identification and immune recognition of viral epitopes,”, S. Kaabinejadian, C. P. McMurtrey, S. Kim et al., “Immunodominant West Nile virus T cell epitopes are fewer in number and fashionably late,”, P. Oyarzun and B. Kobe, “Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production,”, D. Fenoglio, A. Parodi, R. Lavieri et al., “Immunogenicity of GX301 cancer vaccine: four (telomerase peptides) are better than one,”, M. V. Larsen, A. Lelic, R. Parsons et al., “Identification of CD8, C. M. Diez-Rivero and P. A. Reche, “CD8 T cell epitope distribution in viruses reveals patterns of protein biosynthesis,”, Q. Y. Koo, A. M. Khan, K. O. Jung et al., “Conservation and variability of West Nile virus proteins,”, A. Schneeweiss, S. Chabierski, M. Salomo et al., “A DNA vaccine encoding the E protein of West Nile virus is protective and can be boosted by recombinant domain DIII,”, C. A. Sarri, M. Markantoni, C. Stamatis et al., “Genetic contribution of MHC class II genes in susceptibility to West Nile virus infection,”, K. Ramakrishnan and D. R. Flower, “Discriminating antigen and non-antigen using proteome dissimilarity II: viral and fungal antigens,”, K. Ramakrishnan and D. R. Flower, “Discriminating antigen and non-antigen using proteome dissimilarity III: tumour and parasite antigens,”, K. Ramakrishnan and D. R. Flower, “Discriminating antigen and non-antigen using proteome dissimilarity: bacterial antigens,”.
9: 4200-4223. Addition of computational CR prediction to our design-by-selection protocol is a key advance over previous work [14–20] and should accelerate the early selection of safe vaccines. News releases, fact sheets and other NIAID-related materials are available on the NIAID website. To create a potential ‘universal’ vaccine candidate CD8+ and CD4+ epitopes were combined and PPC calculated using IEDB as above.
doi: 10.1016/j.vaccine.2005.03.052.
We evaluated serum from a sample of these horses by the RVP neutralizing antibody assay. The plasmid was based on an analogous construct shown to protect mice and horses from virus challenge [19]. Vaccine-induced humoral immune responses were assessed at weeks 8, 12, and 32. Humans do not carry enough virus to efficiently infect mosquitoes and are unlikely to be the original source, according to Lyle R. Petersen, MD, MPH,Infectious Disease News Editorial Board member and director of the CDC’s Division of Vector-Borne Diseases. Complete West Nile Virus genome sequences for all human variants and lineages were obtained from the National Centre for Biotechnology Information (NCBI) West Nile Virus Variation Database Resource (URL: https://www.ncbi.nlm.nih.gov/genome/viruses/variation/WestNile/). No vaccine or specific antiviral treatments for West Nile virus infection are available. “It is the most significant mosquito-borne illness in the U.S. by far, at this point,” Petersen said. Epitope-based vaccines against WNV remain significantly underexploited. West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever.It is a member of the family Flaviviridae, specifically from the genus Flavivirus, which also contains the Zika virus, dengue virus, and yellow fever virus. All T cell epitopes included in our final vaccine combination were either located in the E protein (VTV18), NS2A (ITY9), NS3 (SYH9), or NS4B (TLA9). Cross-reactivity and human leukocyte antigen-binding affinities were assessed to eliminate unsuitable epitope candidates. Subject B was not assessed at the week 12 time point because of visit noncompliance.
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