Abstract

Immunization is the cornerstone of seasonal influenza control and represents an important component of pandemic preparedness strategies. Using a bioluminescent reporter H1N1pdm09 virus, we demonstrate the application of non-invasive in vivo imaging system (IVIS) technology to evaluate the pre-clinical efficacy of candidate vaccines and immunotherapy in a mouse model of influenza. Sequential imaging revealed distinct spatiotemporal kinetics of bioluminescence between groups of mice that were passively or actively immunized by various strategies that accelerated clearance of challenge virus at different rates and by distinct mechanisms. Imaging findings were consistent with conclusions derived from virus titration from the lungs and, notably, were more informative than conventional efficacy endpoints in some cases. Our findings demonstrate the reliability of IVIS as a qualitative approach to support pre-clinical evaluation of candidate medical countermeasures for influenza in mice.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001109-09
Application #
9566713
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Czakó, Rita; Vogel, Leatrice; Lamirande, Elaine W et al. (2017) In Vivo Imaging of Influenza Virus Infection in Immunized Mice. MBio 8:
Broadbent, Andrew J; Santos, Celia P; Anafu, Amanda et al. (2016) Evaluation of the attenuation, immunogenicity, and efficacy of a live virus vaccine generated by codon-pair bias de-optimization of the 2009 pandemic H1N1 influenza virus, in ferrets. Vaccine 34:563-570
Lakdawala, Seema S; Jayaraman, Akila; Halpin, Rebecca A et al. (2015) The soft palate is an important site of adaptation for transmissible influenza viruses. Nature 526:122-5
O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice et al. (2014) Humans and ferrets with prior H1N1 influenza virus infections do not exhibit evidence of original antigenic sin after infection or vaccination with the 2009 pandemic H1N1 influenza virus. Clin Vaccine Immunol 21:737-46
Broadbent, Andrew J; Santos, Celia P; Godbout, Rachel A et al. (2014) The temperature-sensitive and attenuation phenotypes conferred by mutations in the influenza virus PB2, PB1, and NP genes are influenced by the species of origin of the PB2 gene in reassortant viruses derived from influenza A/California/07/2009 and A/WSN/ J Virol 88:12339-47
Lakdawala, Seema S; Wu, Yicong; Wawrzusin, Peter et al. (2014) Influenza a virus assembly intermediates fuse in the cytoplasm. PLoS Pathog 10:e1003971
Lakdawala, Seema S; Shih, Angela R; Jayaraman, Akila et al. (2013) Receptor specificity does not affect replication or virulence of the 2009 pandemic H1N1 influenza virus in mice and ferrets. Virology 446:349-56
Boonnak, Kobporn; Vogel, Leatrice; Orandle, Marlene et al. (2013) Antigen-activated dendritic cells ameliorate influenza A infections. J Clin Invest 123:2850-61
Harris, Audray K; Meyerson, Joel R; Matsuoka, Yumiko et al. (2013) Structure and accessibility of HA trimers on intact 2009 H1N1 pandemic influenza virus to stem region-specific neutralizing antibodies. Proc Natl Acad Sci U S A 110:4592-7
O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice N et al. (2012) Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus. J Virol 86:8625-33

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