tetano
Editor, Senior Moderator
Vaccine. 2012 Aug 3. [Epub ahead of print]
A replication-incompetent virus possessing an uncleavable hemagglutinin as an influenza vaccine.
Katsura H, Iwatsuki-Horimoto K, Fukuyama S, Watanabe S, Sakabe S, Hatta Y, Murakami S, Shimojima M, Horimoto T, Kawaoka Y.
Source
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Abstract
Vaccination is one of the most effective measures to protect against influenza virus infection. Inactivated and live-attenuated influenza vaccines are available; however, their efficacy is suboptimal. To develop a safe and more immunogenic vaccine, we produced a novel replication-incompetent influenza virus that possesses uncleavable hemagglutinin (HA) and tested its vaccine potential. The uncleavable HA was engineered by substituting the arginine at the C-terminus of HA1 with threonine, which prevents cleavage of HA into its HA1 and HA2 subunits, preventing fusion between the host and viral membranes. Although this fusion-deficient HA influenza virus that possesses uncleavable HA (uncleavable HA virus) could undergo multiple cycles of replication in only wild-type HA-expressing cells, it could infect normal cells and express viral proteins in infected cells, but could not generate infectious virus from infected cells due to the uncleavable HA. When C57BL/6 mice were intranasally immunized with the uncleavable HA virus, influenza-specific IgG and IgA antibodies were detected in nasal wash and bronchoalveolar lavage samples and in serum. In addition, influenza-specific CD8(+) T cells accumulated in the lungs of these mice. Moreover, mice immunized with the uncleavable HA virus were protected against a challenge of lethal doses of influenza virus, unlike mice immunized with a formalin-inactivated virus. These findings demonstrate that this fusion-deficient virus, which possesses uncleavable HA, is a suitable influenza vaccine candidate.
Copyright ? 2012. Published by Elsevier Ltd.
PMID:
22867723
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22867723
A replication-incompetent virus possessing an uncleavable hemagglutinin as an influenza vaccine.
Katsura H, Iwatsuki-Horimoto K, Fukuyama S, Watanabe S, Sakabe S, Hatta Y, Murakami S, Shimojima M, Horimoto T, Kawaoka Y.
Source
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Abstract
Vaccination is one of the most effective measures to protect against influenza virus infection. Inactivated and live-attenuated influenza vaccines are available; however, their efficacy is suboptimal. To develop a safe and more immunogenic vaccine, we produced a novel replication-incompetent influenza virus that possesses uncleavable hemagglutinin (HA) and tested its vaccine potential. The uncleavable HA was engineered by substituting the arginine at the C-terminus of HA1 with threonine, which prevents cleavage of HA into its HA1 and HA2 subunits, preventing fusion between the host and viral membranes. Although this fusion-deficient HA influenza virus that possesses uncleavable HA (uncleavable HA virus) could undergo multiple cycles of replication in only wild-type HA-expressing cells, it could infect normal cells and express viral proteins in infected cells, but could not generate infectious virus from infected cells due to the uncleavable HA. When C57BL/6 mice were intranasally immunized with the uncleavable HA virus, influenza-specific IgG and IgA antibodies were detected in nasal wash and bronchoalveolar lavage samples and in serum. In addition, influenza-specific CD8(+) T cells accumulated in the lungs of these mice. Moreover, mice immunized with the uncleavable HA virus were protected against a challenge of lethal doses of influenza virus, unlike mice immunized with a formalin-inactivated virus. These findings demonstrate that this fusion-deficient virus, which possesses uncleavable HA, is a suitable influenza vaccine candidate.
Copyright ? 2012. Published by Elsevier Ltd.
PMID:
22867723
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22867723