RESUMO
Vaccination is the first line of protection against influenza virus infection in humans. Although inactivated and live-attenuated vaccines are available, each vaccine has drawbacks in terms of immunogenicity and safety. To overcome these issues, our group has developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that replicates only in PB2-expressing cells. Here we generated PB2-KO viruses possessing the hemagglutinin (HA) and neuraminidase (NA) segments from H1N1pdm09 or type B viruses and tested their vaccine potential. The two PB2-KO viruses propagated efficiently in PB2-expressing cells, and expressed chimeric HA as expected. Virus-specific IgG and IgA antibodies were detected in mice immunized with the viruses, and the immunized mice showed milder clinical signs and/or lower virus replication levels in the respiratory tract upon virus challenge. Our results indicate that these PB2-KO viruses have potential as vaccine candidates.
Assuntos
Técnicas de Inativação de Genes , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza B/imunologia , Vacinas contra Influenza/imunologia , Proteínas Virais/genética , Animais , Anticorpos Antivirais/sangue , Modelos Animais de Doenças , Feminino , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza B/genética , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/prevenção & controle , Sistema Respiratório/virologia , Carga ViralRESUMO
A meeting was held at NIBSC, UK in July 2007 to discuss the implications of progress in the use of cell culture systems for the manufacture of vaccines against influenza. Issues discussed included the effect of using eggs and different cell types in strain selection, development of seed viruses to be used in production and the nature of the reagents to be used in determining vaccine potency. Future studies to progress the field were reviewed.