Abstract
Seasonal epidemics of influenza virus result in ∼36,000 deaths annually in the United States. Current vaccines against influenza virus elicit an antibody response specific for the envelope glycoproteins. However, high mutation rates result in the emergence of new viral serotypes, which elude neutralization by preexisting antibodies. T lymphocytes have been reported to be capable of mediating heterosubtypic protection through recognition of internal, more conserved, influenza virus proteins. Here, we demonstrate using a recombinant influenza virus expressing the LCMV GP33-41 epitope that influenza virus-specific CD8+ T cells and virus-specific non-neutralizing antibodies each are relatively ineffective at conferring heterosubtypic protective immunity alone. However, when combined virus-specific CD8 T cells and non-neutralizing antibodies cooperatively elicit robust protective immunity. This synergistic improvement in protective immunity is dependent, at least in part, on alveolar macrophages and/or other lung phagocytes. Overall, our studies suggest that an influenza vaccine capable of eliciting both CD8+ T cells and antibodies specific for highly conserved influenza proteins may be able to provide heterosubtypic protection in humans, and act as the basis for a potential “universal” vaccine.
Highlights
Influenza virus remains a significant threat to global health, and results in 200,000 hospitalizations and 3,000–49,000 deaths each year in the United States [1,2,3]
We found that the lymphocytic choriomeningitis virus (LCMV) Armstrong immune mice had a similar or slightly larger antiviral CD8+ T cell response directed against the recombinant influenza virus following rechallenge in both the lung and bronchoalveolar lavage (BAL) despite lack of protection (Fig. 1B)
It is important to note that while we found clodronate liposome treatment to be non-toxic to uninfected mice and to result in,70% depletion of alveolar macrophages in the BAL fluid three days following a single clodronate treatment (Fig. S5B), it is possible that depletion of other airway populations such as dendritic cell or inflammatory macrophages could occur
Summary
Influenza virus remains a significant threat to global health, and results in 200,000 hospitalizations and 3,000–49,000 deaths each year in the United States [1,2,3]. The ability of influenza virus to rapidly mutate and/or undergo reassortment, allows the virus to evade protective immunity obtained from previous infections or vaccinations [4]. Annual influenza vaccines induce an antibody response specific for the highly variable surface glycoproteins of influenza: neuraminidase (NA) and hemagglutinin (HA). These seasonal vaccines typically take months to produce and rely on the accurate prediction of the influenza serotypes that will be circulating in the flu season [5]. Much research has focused on the development of a ‘‘universal’’ vaccine that will target the conserved, internal regions of the influenza virus, and confer protection against multiple influenza virus serotypes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
