Oligomerization of Bacterially Expressed H1N1 Recombinant Hemagglutinin Contributes to Protection Against Viral Challenge

Authors

Tess E. Kuenstling, University of Nebraska Medical Center
Anthony R. Sambol, University of Nebraska Medical CenterFollow
Steven H. Hinrichs, University of Nebraska Medical CenterFollow
Marilynn A. Larson, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Scientific Reports

Publication Date

2018

Volume

8

Abstract

Vaccination is the most effective intervention to prevent influenza and control the spread of the virus. Alternatives are needed to the traditional egg-based vaccine strategy for a more rapid response to new outbreaks. Two different hemagglutinin (HA) fragments (rHA1_1-326 and rHA1_53-269) derived from influenza A virus subtype H1N1 were expressed in Escherichia coli and characterized by immunoblot, gel filtration, hemagglutination, and competitive binding assays. rHA1_1-326 included neutralizing epitopes and the trimerization domain, whereas rHA1_53-269 included only the head of HA with the neutralizing epitopes. Mice were immunized with rHA1_1-326 or rHA1_53-269, and sera were tested for the presence of neutralizing antibodies. Mice were then challenged with H1N1 and infection severity was monitored. rHA1_1-326 trimerized, whereas rHA1_53-269 was unable to form oligomers. Both rHA1_1-326 and rHA1_53-269 elicited the production of neutralizing antibodies, but only oligomerized rHA1_1-326 protected against live virus challenges in mice. This study demonstrated that bacterially expressed HA was capable of folding properly and eliciting the production of neutralizing antibodies, and that HA oligomerization contributed to protection against viral challenge. Therefore, prokaryotic-derived vaccine platforms can provide antigenic and structural requirements for viral protection, as well as allow for the rapid and cost-effective incorporation of multiple antigens for broader protection.

DOI Link

10.1038/s41598-018-30079-4

ISSN

2045-2322

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Kuenstling, Tess E.; Sambol, Anthony R.; Hinrichs, Steven H.; and Larson, Marilynn A., "Oligomerization of Bacterially Expressed H1N1 Recombinant Hemagglutinin Contributes to Protection Against Viral Challenge" (2018). Journal Articles: Pathology and Microbiology. 61.
https://digitalcommons.unmc.edu/com_pathmicro_articles/61