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Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Egg-adapted replication-restricted virus protects mice against lethal influenza
1Department of Microbiology, Fukui Medical University School of Medicine, Shimoaizuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Abstract:
Infection of mice with the egg-adapted (EA) strain of influenza virus was studied as a murine model of human live attenuated virus vaccine. The growth and spread of the EA virus in the mouse lungs were restricted, and only small inflammatory changes were detected in the respiratory tracts. Deletion and substitutions of amino acids were found in the hemagglutinin molecule of the EA virus, which were attributable to the reduced envelope fusion activity in virus multiplication cycles. Intranasal inoculation of mice with the EA virus induced specific IgG and IgA antibody production together with a specific cytotoxic T lymphocyte response. Immunized mice showed a distinct resistance to subsequent lethal challenge with the virulent influenza virus. These results indicate that the mutant virus loaded with a growth restriction in the respiratory tract is an appropriate candidate for a live attenuated vaccine.
Insights
This study explored an egg-adapted (EA) influenza virus strain in mice as a potential live attenuated vaccine. The EA virus showed restricted growth and induced protective immunity against virulent influenza, suggesting its vaccine candidacy.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Live attenuated virus vaccines offer advantages in inducing broad immunity.
- Developing safe and effective live attenuated influenza vaccines remains a priority.
Purpose of the Study:
- To evaluate the egg-adapted (EA) influenza virus strain as a murine model for a live attenuated vaccine.
- To assess the immunogenicity and protective efficacy of the EA strain in mice.
Main Methods:
- Infection of mice with the EA strain of influenza virus.
- Analysis of viral growth, spread, and inflammatory changes in respiratory tracts.
- Assessment of humoral (IgG, IgA) and cellular (cytotoxic T lymphocyte) immune responses.
- Evaluation of protection against subsequent challenge with virulent influenza virus.
Main Results:
- The EA virus exhibited restricted growth and limited inflammation in mouse lungs.
- Amino acid alterations in the hemagglutinin molecule correlated with reduced fusion activity.
- Intranasal inoculation induced specific antibody and cytotoxic T lymphocyte responses.
- Immunized mice demonstrated significant resistance to lethal influenza challenge.
Conclusions:
- The EA influenza virus strain, with its inherent growth restriction, serves as a suitable candidate for a live attenuated vaccine.
- The observed immunogenicity and protective effects support its potential for human use.

