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3.
Med Hypotheses ; 143: 110084, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32663741

RESUMO

COVID-19 is the pandemic outbreak that is caused by SARS-CoV-2 virus from December, 2019. Human race do not know the curative measure of this devastating disease. In today's era of nanotechnology, it may use its knowledge to develop molecular vaccine to combat this disease. In this article we are intended to propose a hypothesis on the development of a vaccine that is molecular in nature to work against COVID-19. The nanoconjugate may comprise with the inorganic nanoparticle layered double hydroxide intercalated with shRNA-plasmid that have a sequence targeting towards the viral genome or viral mRNA. This nanoconjugate may be used as a nasal spray to deliver the shRNA-plasmid to the target site. The nanoconjugate will have several advantages such as they are biocompatible, they forms as stable knockdown to the target cells and they are stable in the nasal mucosa.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/genética , Betacoronavirus/genética , Betacoronavirus/imunologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Modelos Biológicos , Nanoconjugados/química , Plasmídeos/genética , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , RNA Interferente Pequeno/genética , RNA Viral/genética , Vacinas Sintéticas/química , Vacinas Sintéticas/genética , Vacinas Virais/síntese química
4.
Lett Appl Microbiol ; 69(4): 237-245, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31376169

RESUMO

An evaluation of the efficacy of 35% hydrogen peroxide vapour (HPV) against two strains of FMDV was conducted over a period of 6 months. FMDV biological indicators were produced on-site using strains obtained from a commercial FMDV vaccine manufacturing process. FMDV biological indicators were distributed within a BSL4 laboratory and exposed to short duration hydrogen peroxide cycles. Variations in titre, support matrix (soiling), temperature and humidity were evaluated in a series of 16 exposures using over 200 individual FMDV indicators. Additional verification testing was performed in an operational material transfer lock to replicate real-world use. HPV was found to be efficacious in inactivating FMDV strains; the inoculum titre influenced the level of reduction achieved with the specified cycle. SIGNIFICANCE AND IMPACT OF THE STUDY: The classification of formaldehyde as a presumed human carcinogen has presented regulatory challenges for its continued use as a biocidal product. Institutions are actively seeking fumigants to replace formaldehyde and undertaking studies to validate biocidal efficacy, particularly in high-level biosafety facilities where the consequences of pathogen release can be extremely severe. This study builds on the already substantial scientific efficacy base of 35% hydrogen peroxide vapour and provides a comprehensive evaluation of the applicability of hydrogen peroxide vapour as a replacement for formaldehyde within a Foot & Mouth Disease (FMDV) vaccine manufacturing facility.


Assuntos
Vírus da Febre Aftosa/efeitos dos fármacos , Febre Aftosa/prevenção & controle , Formaldeído/farmacologia , Peróxido de Hidrogênio/farmacologia , Vacinas Virais/síntese química , Animais , Febre Aftosa/virologia , Gases/farmacologia , Umidade , Instalações Industriais e de Manufatura
5.
Infect Genet Evol ; 70: 140-157, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30849525

RESUMO

Marburg virus is known to cause a severe hemorrhagic fever (MHF) in both humans and non-human primates with high degree of infectivity and lethality. To date no approved treatment is available for Marburg virus infection. A study was employed to design a novel chimeric subunit vaccine against Marburg virus by adopting reverse vaccinology approach. The entire viral proteome was retrieved from UniprotKB and assessed to design highly antigenic epitopes by antigenicity screening, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach. Envelope glycoprotein (GP) and matrix protein (VP40) were identified as most antigenic viral proteins which generated a plethora of epitopes. The final vaccine was constructed by the combination of highly immunogenic epitopes along with suitable adjuvant and linkers. Physicochemical and secondary structure of the designed vaccine was assessed to ensure its thermostability, hydrophilicity, theoretical PI and structural behaviors. Disulfide engineering, molecular dynamic simulation and codon adaptation were further employed to develop a unique multi-epitope monovalent vaccine. Docking analysis of the refined vaccine structure with different MHC molecules and human immune TLR8 receptor present on lymphocyte cells demonstrated higher interaction. Moreover, disulfide engineering served to lessen the high mobility region of the designed vaccine in order to extend its stability. Complexed structure of the modeled vaccine and TLR8 showed minimal deformability at molecular level. Finally, translational potency and microbial expression of the modeled vaccine was analyzed with pET28a(+) vector for E. coli strain K12. However, further in vitro and in vivo investigation could be implemented for the acceptance and validation of the predicted vaccine against Marburg virus.


Assuntos
Desenho de Fármacos , Doença do Vírus de Marburg/tratamento farmacológico , Marburgvirus/imunologia , Vacinas Virais/síntese química , Animais , Antígenos Virais/imunologia , Biologia Computacional , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas do Envelope Viral/imunologia , Vacinas Virais/imunologia
6.
J Cell Physiol ; 234(5): 6437-6448, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30362500

RESUMO

Cancer is one of the common lifestyle diseases and is considered to be the leading cause of death worldwide. Epstein-Barr virus (EBV)-infected individuals remain asymptomatic; but under certain stress conditions, EBV may lead to the development of cancers such as Burkitt's and Hodgkin's lymphoma and nasopharyngeal carcinoma. EBV-associated cancers result in a large number of deaths in Asian and African population, and no effective cure has still been developed. We, therefore, tried to devise a subunit vaccine with the help of immunoinformatic approaches that can be used for the prevention of EBV-associated malignancies. The epitopes were predicted through B-cell, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) from the different oncogenic proteins of EBV. A vaccine was designed by combining the B-cell and T-cell (HTL and CTL) epitopes through linkers, and for the enhancement of immunogenicity, an adjuvant was added at the N-terminal. Further, homology modeling was performed to generate the 3D structure of the designed vaccine. Moreover, molecular docking was performed between the designed vaccine and immune receptor (TLR-3) to determine the interaction between the final vaccine construct and the immune receptor complex. In addition, molecular dynamics was performed to analyze the stable interactions between the ligand final vaccine model and receptor TLR-3 molecule. Lastly, to check the expression of our vaccine construct, we performed in silico cloning. This study needed experimental validation to ensure its effectiveness and potency to control malignancy.


Assuntos
Mapeamento de Epitopos/métodos , Infecções por Vírus Epstein-Barr/prevenção & controle , Proteínas não Estruturais Virais/imunologia , Vacinas Virais , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4 , Humanos , Simulação de Acoplamento Molecular , Vacinas de Subunidades/síntese química , Vacinas Virais/síntese química , Vacinas Virais/química , Vacinas Virais/imunologia
7.
Comput Biol Chem ; 68: 143-152, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28342423

RESUMO

The Zika virus infections have reached epidemic proportions in the Latin American countries causing severe birth defects and neurological disorders. While several organizations have begun research into design of prophylactic vaccines and therapeutic drugs, computer assisted methods with adequate data resources can be expected to assist in these measures to reduce lead times through bioinformatics approaches. Using 60 sequences of the Zika virus envelope protein available in the GenBank database, our analysis with numerical characterization techniques and several web based bioinformatics servers identified four peptide stretches on the Zika virus envelope protein that are well conserved and surface exposed and are predicted to have reasonable epitope binding efficiency. These peptides can be expected to form the basis for a nascent peptide vaccine which, enhanced by incorporation of suitable adjuvants, can elicit immune response against the Zika virus infections.


Assuntos
Biologia Computacional , Desenho de Fármacos , Peptídeos/imunologia , Vacinas Virais/imunologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , Adjuvantes Imunológicos , Epitopos/química , Epitopos/imunologia , Peptídeos/síntese química , Peptídeos/química , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Vacinas Virais/síntese química , Vacinas Virais/química , Zika virus/química , Zika virus/genética , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologia
8.
Vopr Virusol ; 61(1): 5-8, 2016.
Artigo em Russo | MEDLINE | ID: mdl-27145593
9.
Viruses ; 7(7): 3954-73, 2015 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-26193305

RESUMO

The innate immune system is the first line of defense against viral infections. Exploiting innate responses for antiviral, therapeutic and vaccine adjuvation strategies is being extensively explored. We have previously described, the ability of small in vitro RNA transcripts, mimicking the sequence and structure of different domains in the non-coding regions of the foot-and-mouth disease virus (FMDV) genome (ncRNAs), to trigger a potent and rapid innate immune response. These synthetic non-infectious molecules have proved to have a broad-range antiviral activity and to enhance the immunogenicity of an FMD inactivated vaccine in mice. Here, we have studied the involvement of pattern-recognition receptors (PRRs) in the ncRNA-induced innate response and analyzed the antiviral and cytokine profiles elicited in swine cultured cells, as well as peripheral blood mononuclear cells (PBMCs).


Assuntos
RNA Helicases DEAD-box/imunologia , Vírus da Febre Aftosa/imunologia , Febre Aftosa/imunologia , Imunidade Inata , RNA Viral/imunologia , Receptores Toll-Like/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , RNA Helicases DEAD-box/genética , Feminino , Febre Aftosa/genética , Febre Aftosa/prevenção & controle , Febre Aftosa/virologia , Vírus da Febre Aftosa/genética , Leucócitos Mononucleares/imunologia , Masculino , Camundongos , RNA Viral/administração & dosagem , RNA Viral/síntese química , RNA Viral/genética , Suínos , Receptores Toll-Like/genética , Vacinas Virais/administração & dosagem , Vacinas Virais/síntese química , Vacinas Virais/genética
10.
Int J Nanomedicine ; 10: 2895-911, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25926734

RESUMO

Layered double hydroxide (LDH)@SiO2 nanoparticles were developed as a delivery carrier for the plasmid DNA expressing the Newcastle disease virus F gene. The LDH was hydrotalcite-like materials. The plasmid DNA encapsulated in the LDH@SiO2 nanoparticles (pFDNA-LDH@SiO2-NPs) was prepared by the coprecipitation method, and the properties of pFDNA-LDH@SiO2-NPs were characterized by transmission electron microscopy, zeta potential analyzer, Fourier transform infrared spectroscopy, and X-ray diffraction analysis. The results demonstrated that the pFDNA-LDH@SiO2-NPs had a regular morphology and high stability with a mean diameter of 371.93 nm, loading capacity of 39.66%±0.45%, and a zeta potential of +31.63 mV. A release assay in vitro showed that up to 91.36% of the total plasmid DNA could be sustainably released from the pFDNA-LDH@SiO2-NPs within 288 hours. The LDH@SiO2 nanoparticles had very low toxicity. Additionally, their high transfection efficiency in vitro was detected by fluorescent microscopy. Intranasal immunization of specific pathogen-free chickens with pFDNA-LDH@SiO2-NPs induced stronger cellular, humoral, and mucosal immune responses and achieved a greater sustained release effect than intramuscular naked plasmid DNA, and the protective efficacy after challenge with the strain F48E9 with highly virulent (mean death time of chicken embryos ≤60 hours, intracerebral pathogenicity index in 1 -day-old chickens >1.6) was 100%. Based on the results, LDH@SiO2 nanoparticles can be used as a delivery carrier for mucosal immunity of Newcastle disease DNA vaccine, and have great application potential in the future.


Assuntos
Nanopartículas/química , Doença de Newcastle , Vírus da Doença de Newcastle/genética , Vacinas de DNA , Vacinas Virais , Animais , Galinhas , DNA Viral/genética , Hidróxidos/química , Doença de Newcastle/imunologia , Doença de Newcastle/prevenção & controle , Doença de Newcastle/virologia , Plasmídeos , Dióxido de Silício/química , Transfecção , Vacinas de DNA/síntese química , Vacinas de DNA/química , Vacinas de DNA/imunologia , Vacinas Virais/síntese química , Vacinas Virais/química , Vacinas Virais/imunologia
11.
Antiviral Res ; 109: 64-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24973761

RESUMO

In this work we have addressed the effect of synthetic, non-infectious, RNA transcripts, mimicking structural domains of the non-coding regions (NCRs) of the foot-and-mouth disease virus (FMDV) genome on the infection of mice with Rift Valley fever virus (RVFV). Groups of 5 mice were inoculated intraperitoneally (i.p.) with 200 µg of synthetic RNA resembling the 5'-terminal S region, the internal ribosome entry site (IRES) or the 3'-NCR of the FMDV genome. RNA inoculation was performed 24h before (-24 h), 24 h after (+24 h) or simultaneously to the challenge with a lethal dose of RVFV. Administration of the IRES RNA afforded higher survival rates than administration of S or 3'NCR transcripts either at -24h or +24h after challenge. In contrast, when RNA inoculation and viral challenge were performed simultaneously, all mice survived in both IRES- and 3'NCR-inoculated groups, with an 80% survival in mice receiving the S RNA. Among survivors, a complete correlation between significant anti-RVFV circulating antibody titers and resistance to a second lethal challenge with the virus was observed, supporting a limited viral replication in the RNA-inoculated animals upon the first challenge. All three RNA transcripts were able to induce the production of systemic antiviral and pro-inflammatory cytokines. These data show that triggering of intracellular pathogen sensing pathways constitutes a promising approach towards development of novel RVF preventive or therapeutic strategies.


Assuntos
Vírus da Febre Aftosa/genética , Interferons/administração & dosagem , RNA Viral/imunologia , Febre do Vale de Rift/prevenção & controle , Vírus da Febre do Vale do Rift/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Proteção Cruzada , Vírus da Febre Aftosa/imunologia , Genoma Viral , Humanos , Camundongos , Camundongos Endogâmicos BALB C , RNA Viral/administração & dosagem , RNA Viral/síntese química , RNA Viral/genética , Febre do Vale de Rift/imunologia , Febre do Vale de Rift/virologia , Vírus da Febre do Vale do Rift/fisiologia , Vacinação , Vacinas Virais/administração & dosagem , Vacinas Virais/síntese química , Vacinas Virais/genética , Replicação Viral
12.
Methods ; 60(3): 226-31, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23623821

RESUMO

Nanosized particles including nanovaccines are a novel approach to the development of vaccines to combat diseases. Nanovaccines have the promise to utilize the immune system to cure infections and to prevent infections and diseases from spreading. Rational vaccine development requires an understanding of vaccine mediated stimulation of the immune system. We review here immunostimulatory properties of nanovaccines including their immunogenicity, adjuvant properties, inflammatory responses and the mechanisms of uptake and stimulation of immune cells. Examples of various nanoparticles currently being developed as vaccines are also provided.


Assuntos
Antígenos/imunologia , Vacinas Bacterianas/imunologia , Sistema Imunitário , Vacinas Virais/imunologia , Adjuvantes Imunológicos/química , Vacinas Bacterianas/síntese química , Dendrímeros/química , Fulerenos/química , Fulerenos/imunologia , Humanos , Lipossomos/química , Lipossomos/imunologia , Nanopartículas Metálicas/química , Nanotubos/química , Vacinas Virais/síntese química
13.
Postepy Hig Med Dosw (Online) ; 67: 1345-58, 2013 Jan 11.
Artigo em Polonês | MEDLINE | ID: mdl-24379275

RESUMO

Vesicular stomatitis virus (VSV), a member of the Rhabdoviridae family, is a promising candidate for potential use in construction of antiviral vaccines. In the natural environment VSV is a pathogen of wild ungulates and livestock. Some of the features that make VSV an excellent platform for the development of a range of viral therapeutics includes its immunogenicity and ability to grow to high titers in cell lines approved for vaccine use. Infection in humans is rare and usually asymptomatic, with mild flu-like symptoms. Moreover, due to affinity of VSV envelope glycoprotein to the LDL (low-density lipoprotein) receptor, VSV is effective at targeting a variety of tissues in vivo. A series of research results confirm the possibility of developing VSV-based vaccines against human papilloma viruses (HPV), human immunodeficiency virus (HIV), hepatitis B virus (HBV) and filoviruses (MARV, ZEBOV and SEBOV), as well as the potential use of a successfully developed vaccine against hepatitis C virus (HCV). VSV is neurotropic and infection can cause a viral encephalitis in experimental animals. Therefore, intensive studies are being undertaken to achieve satisfactory expression of the viral antigens while maintaining the safety of the constructed vectors.


Assuntos
Estomatite Vesicular/virologia , Vírus da Estomatite Vesicular Indiana/imunologia , Vacinas Virais/síntese química , Vacinas Virais/imunologia , Animais , Vetores Genéticos , Humanos , Vírus da Estomatite Vesicular Indiana/genética
14.
Curr Top Med Chem ; 12(12): 1310-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22690678

RESUMO

With the recent onset of influenza A (H1N1) pandemic, the need for improved vaccines against virus infections has become an international priority. Strategies for vaccine development have changed over time, from whole-virus to immunogenic proteins and further to antigenic viral peptides. Various algorithms and bioinformatics tools have been developed to predict immunogenic peptide regions in an antigenic protein sequence. Recent advances in next-generation sequencing technologies, as represented by real time DNA sequencing, provide increased throughput and yield of data on viral pathogens and host cells. This enables us to 'mine' the genomic sequence for putative vaccine candidates or targets, allowing a more rational approach to the peptide vaccine design. This review first describes current computational tools available for the rational design of peptide vaccines and then addresses recent attempts to define pathogenic peptides at '- omics' level. As there are interplay between antibody and T cells, as well as intersection between viruses and hosts, the vaccine-mediated immunity are orchestrated by multiple factors within an interaction network. Therefore, single viral peptide alone fails to provide optimal immunity. Systems biology offers a systems-level perspective of how the various arms of the immune response are integrated to give immune response, as well as how host and virus interact, thereby providing an integrated approach to select the most promising candidates for peptide vaccines development. We highlight in this article the system-level application of rational peptide vaccine design, which may be a general paradigm for future viral vaccine development.


Assuntos
Desenho de Fármacos , Biologia de Sistemas , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia , Viroses/imunologia , Algoritmos , Animais , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Vacinas de Subunidades/síntese química , Vacinas de Subunidades/química , Vacinas Virais/síntese química , Vacinas Virais/química , Viroses/prevenção & controle , Viroses/virologia
15.
Nat Biotechnol ; 28(6): 573-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20531338

RESUMO

The design of vaccines against viral disease has evolved considerably over the past 50 years. Live attenuated viruses (LAVs)-those created by passaging a virus in cultured cells-have proven to be an effective means for preventing many viral diseases, including smallpox, polio, measles, mumps and yellow fever. Even so, empirical attenuation is unreliable in some cases and LAVs pose several safety issues. Although inactivated viruses and subunit vaccines alleviate many of these concerns, they have in general been less efficacious than their LAV counterparts. Advances in molecular virology--creating deleterious gene mutations, altering replication fidelity, deoptimizing codons and exerting control by microRNAs or zinc finger nucleases--are providing new ways of controlling viral replication and virulence and renewing interest in LAV vaccines. Whereas these rationally attenuated viruses may lead to a new generation of safer, more widely applicable LAV vaccines, each approach requires further testing before progression to human testing.


Assuntos
Vacinas Atenuadas/síntese química , Vacinas Virais/síntese química , Deleção de Genes , Humanos , MicroRNAs/metabolismo , Viroses/prevenção & controle , Dedos de Zinco
17.
BMC Biotechnol ; 7: 56, 2007 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-17850660

RESUMO

BACKGROUND: We have investigated the possibility and feasibility of producing the HPV-11 L1 major capsid protein in transgenic Arabidopsis thaliana ecotype Columbia and Nicotiana tabacum cv. Xanthi as potential sources for an inexpensive subunit vaccine. RESULTS: Transformation of plants was only achieved with the HPV-11 L1 gene with the C-terminal nuclear localization signal (NLS-) encoding region removed, and not with the full-length gene. The HPV-11 L1 NLS- gene was stably integrated and inherited through several generations of transgenic plants. Plant-derived HPV-11 L1 protein was capable of assembling into virus-like particles (VLPs), although resulting particles displayed a pleomorphic phenotype. Neutralising monoclonal antibodies binding both surface-linear and conformation-specific epitopes bound the A. thaliana-derived particles and - to a lesser degree - the N. tabacum-derived particles, suggesting that plant-derived and insect cell-derived VLPs displayed similar antigenic properties. Yields of up to 12 microg/g of HPV-11 L1 NLS- protein were harvested from transgenic A. thaliana plants, and 2 microg/g from N. tabacum plants - a significant increase over previous efforts. Immunization of New Zealand white rabbits with approximately 50 microg of plant-derived HPV-11 L1 NLS- protein induced an antibody response that predominantly recognized insect cell-produced HPV-11 L1 NLS- and not NLS+ VLPs. Evaluation of the same sera concluded that none of them were able to neutralise pseudovirion in vitro. CONCLUSION: We expressed the wild-type HPV-11 L1 NLS- gene in two different plant species and increased yields of HPV-11 L1 protein by between 500 and 1000-fold compared to previous reports. Inoculation of rabbits with extracts from both plant types resulted in a weak immune response, and antisera neither reacted with native HPV-11 L1 VLPs, nor did they neutralise HPV-11 pseudovirion infectivity. This has important and potentially negative implications for the production of HPV-11 vaccines in plants.


Assuntos
Arabidopsis/metabolismo , Proteínas do Capsídeo/biossíntese , Proteínas Oncogênicas Virais/biossíntese , Plantas Geneticamente Modificadas/metabolismo , Tabaco/metabolismo , Animais , Anticorpos Antivirais , Arabidopsis/genética , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/isolamento & purificação , Expressão Gênica , Papillomavirus Humano 11/genética , Humanos , Testes de Neutralização , Proteínas Oncogênicas Virais/imunologia , Proteínas Oncogênicas Virais/isolamento & purificação , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Plantas Geneticamente Modificadas/genética , Engenharia de Proteínas/métodos , Coelhos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Tabaco/genética , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/síntese química , Vacinas Virais/genética , Montagem de Vírus
18.
Expert Rev Vaccines ; 6(1): 57-74, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17280479

RESUMO

Marburg (MARV) and Ebola viruses (EBOV) emerged from the rainforests of Central Africa more than 30 years ago causing outbreaks of severe and, usually, fatal hemorrhagic fever. EBOV has garnered the lion's share of the attention, fueled by the higher frequency of EBOV outbreaks, high mortality rates and importation into the USA, documented in such popular works as the best-selling novel 'The Hot Zone'. However, recent large outbreaks of hundreds of cases of MARV infection in the Democratic Republic of the Congo and Angola with case fatalities approaching 90% dramatically highlight its lethal potential. Although no vaccines or antiviral drugs for MARV are currently available, remarkable progress has been made over the last few years in developing potential countermeasures against MARV in nonhuman primate models. In particular, a vaccine based on attenuated recombinant vesicular stomatitis virus was recently shown to have both preventive and postexposure efficacy.


Assuntos
Doença do Vírus de Marburg/prevenção & controle , Marburgvirus/efeitos dos fármacos , Vacinas Virais/síntese química , Vacinas Virais/uso terapêutico , Angola/epidemiologia , Animais , República Democrática do Congo/epidemiologia , Surtos de Doenças/prevenção & controle , Humanos , Doença do Vírus de Marburg/epidemiologia , Vacinação em Massa/métodos , Vacinação em Massa/tendências
19.
Expert Rev Vaccines ; 6(1): 87-95, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17280481

RESUMO

Jenner's original vaccine used cowpox virus. Cowpox virus and, subsequently, vaccinia virus, a closely related Orthopoxvirus, provided the means to eradicate smallpox. This history and the unique properties of the virus suggest that vaccinia virus will continue to provide a useful vaccine platform. Yet, surprisingly, it has become apparent that much of the virus genome encodes accessory proteins that interfere with host immune responses to infection. Manipulation of these genes offers the potential for new generations of orthopoxvirus vaccines in which we will have far greater control over key features of the vaccination, including the sites of virus infection, the degree of virus replication, the pathogenicity of the virus and, most importantly, the suppression or induction of immune responses of specific types.


Assuntos
Orthopoxvirus/genética , Orthopoxvirus/imunologia , Vacinas Virais/síntese química , Vacinas Virais/imunologia , Animais , Desenho de Fármacos , Humanos , Orthopoxvirus/efeitos dos fármacos , Infecções por Poxviridae/genética , Infecções por Poxviridae/imunologia , Infecções por Poxviridae/prevenção & controle , Vírus Vaccinia/efeitos dos fármacos , Vírus Vaccinia/genética , Vírus Vaccinia/imunologia
20.
Mol Immunol ; 44(6): 1253-61, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16930710

RESUMO

Attempts to develop peptide vaccines, based on a limited number of peptides face two problems: HLA polymorphism and the high mutation rate of viral epitopes. We have developed a new genomic method that ensures maximal coverage and thus maximal applicability of the peptide vaccine. The same method also promises a large number of epitopes per HLA to prevent escape via mutations. Our design can be applied swiftly in order to face rapidly emerging viral diseases. We use a genomic scan of all candidate peptides and join them optimally. For a given virus, we use algorithms computing: peptide cleavage probability, transfer through TAP and MHC binding for a large number of HLA alleles. The resulting peptide libraries are pruned for peptides that are not conserved or are too similar to self peptides. We then use a genetic algorithm to produce an optimal protein composed of peptides from this list properly ordered for cleavage. The selected peptides represent an optimal combination to cover all HLA alleles and all viral proteins. We have applied this method to HCV and found that some HCV proteins (mainly envelope proteins) represent much less peptide than expected. A more detailed analysis of the peptide variability shows a balance between the attempts of the immune system to detect less mutating peptides, and the attempts of viruses to mutate peptides and avoid detection by the immune system. In order to show the applicability of our method, we have further used it on HIV-I, Influenza H3N2 and the Avian Flu Viruses.


Assuntos
Biologia Computacional , Desenho de Fármacos , Epitopos/imunologia , Genoma Viral , Antígenos de Histocompatibilidade Classe I/genética , Polimorfismo Genético , Vacinas Virais/imunologia , Vírus/imunologia , Sequência de Aminoácidos , Animais , Epitopos/química , Epitopos/genética , Hepacivirus/genética , Antígenos de Histocompatibilidade Classe I/química , Humanos , Camundongos , Dados de Sequência Molecular , Vacinas de Subunidades/síntese química , Vacinas de Subunidades/imunologia , Vacinas Virais/síntese química , Vírus/genética
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