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1.
Vopr Virusol ; 51(4): 45-8, 2006.
Artigo em Russo | MEDLINE | ID: mdl-16929599
2.
Lancet ; 363(9427): 2122-7, 2004 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-15220033

RESUMO

BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) in 2002 was caused by a previously unknown coronavirus-SARS coronavirus (SARS-CoV). We have developed an experimental SARS vaccine for direct immunisation of the respiratory tract, the major site of SARS- coronavirus transmission and disease. METHODS: We expressed the complete SARS coronavirus envelope spike (S) protein from a recombinant attenuated parainfluenza virus (BHPIV3) that is being developed as a live attenuated, intranasal paediatric vaccine against human parainfluenza virus type 3 (HPIV3). We immunised eight African green monkeys, four with a single dose of BHPIV3/ SARS-S and four with a control, BHPIV3/Ctrl, administered via the respiratory tract. A SARS-coronavirus challenge was given to all monkeys 28 days after immunisation. FINDINGS: Immunisation of animals with BHPIV3/SARS-S induced the production of SARS-coronavirus-neutralising serum antibodies, indicating that a systemic immune response resulted from mucosal immunisation. After challenge with SARS coronavirus, all monkeys in the control group shed SARS coronavirus, with shedding lasting 5-8 days. No viral shedding occurred in the group immunised with BHPIV3/SARS-S. INTERPRETATION: A vectored mucosal vaccine expressing the SARS-coronavirus S protein alone may be highly effective in a single-dose format for the prevention of SARS.


Assuntos
Vírus da Parainfluenza 3 Bovina/imunologia , Mucosa Respiratória/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Vacinação , Vacinas Virais/imunologia , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Chlorocebus aethiops , DNA Recombinante , Imunidade nas Mucosas , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Mucosa Nasal/virologia , Vacinas contra Parainfluenza , Vírus da Parainfluenza 3 Bovina/isolamento & purificação , Vírus da Parainfluenza 3 Bovina/metabolismo , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/isolamento & purificação , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/metabolismo , Síndrome Respiratória Aguda Grave/imunologia , Glicoproteína da Espícula de Coronavírus , Irrigação Terapêutica , Traqueia , Vacinas Atenuadas , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/metabolismo , Vacinas Virais/administração & dosagem
3.
J Gen Virol ; 84(Pt 8): 2153-2162, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12867647

RESUMO

Parainfluenza virus type 3 (PIV3) and respiratory syncytial virus (RSV) are the main causes of ubiquitous acute respiratory diseases of infancy and early childhood, causing 20-25 % of pneumonia and 45-50 % of bronchiolitis in hospitalized children. The primary goal of this study was to create an effective and safe RSV vaccine based on utilizing attenuated bovine PIV3 (bPIV3) as a virus vector backbone. bPIV3 had been evaluated in human clinical trials and was shown to be attenuated and immunogenic in children as young as 2 months of age. The ability of bPIV3 to function as a virus vaccine vector was explored further by introducing the RSV attachment (G) and fusion (F) genes into the bPIV3 RNA genome. The resulting virus, bPIV3/RSV(I), contained an insert of 2900 nt, comprising two translationally competent transcription units. Despite this increase in genetic material, the virus replicated to high titres in Vero cells. This recombinant virus expressed the RSV G and F proteins sufficiently to evoke a protective immune response in hamsters upon challenge with RSV or human PIV3 and to elicit RSV neutralizing and PIV3 haemagglutinin inhibition serum antibodies. In effect, a bivalent vaccine was produced that could protect vaccinees from RSV as well as PIV3. Such a vaccine would vastly reduce the respiratory disease burden, the associated hospitalization costs and, most importantly, decrease morbidity and mortality of infants, immunocompromised individuals and the elderly.


Assuntos
Vetores Genéticos , Vírus da Parainfluenza 3 Bovina/genética , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/imunologia , Proteínas Virais/metabolismo , Animais , Anticorpos Antivirais/sangue , Bovinos , Linhagem Celular , Cricetinae , Testes de Inibição da Hemaglutinação , Humanos , Testes de Neutralização , Vírus da Parainfluenza 3 Bovina/metabolismo , Vírus da Parainfluenza 3 Humana/patogenicidade , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Vacinas contra Vírus Sincicial Respiratório/genética , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/metabolismo , Vírus Sincicial Respiratório Humano/patogenicidade , Infecções por Respirovirus/prevenção & controle , Proteínas Virais/genética , Proteínas Virais/imunologia
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