Abstract
Due to the high mutation and recombination rates of the influenza virus, current clinically licensed influenza vaccines and anti-influenza drugs provide limited protection against the emerging influenza virus epidemic. Therefore, universal influenza vaccines with high efficacy are urgently needed to ensure human safety and health. Passive immunization of influenza broadly neutralizing antibodies may become an ideal option for controlling influenza infection. CR9114 isolated from the peripheral blood mononuclear cells of healthy donors is a broadly neutralizing monoclonal antibody that targets different types of influenza viruses. As the adenovirus vector is one of the most promising delivery vehicles, we employed the chimpanzee adenoviral vector, AdC68, to express CR9114 as a universal anti-influenza vaccine, termed AdC68-CR9114, and evaluated its antibody expression and its broad spectrum of prophylactic and therapeutic effects in animal models. Based on our findings, AdC68-CR9114-infected cell expressed the broadly neutralizing antibody at a high level in vitro and in vivo, exhibited biological functions, and protected mice from different types of influenza virus infection at different time points. The findings from this study shed light on a new strategy for controlling and preventing influenza infection.
Highlights
The influenza virus continues to serve as a severe threat to human health
The CR9114 antibody was purified from the supernatant of infected HEK293 cells using a protein A column and subjected to reducing sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) with Coomassie Blue R-250 staining
Sandwich ELISA was performed to measure the concentration of CR9114 in the supernatant of infected HEK293 cells
Summary
The influenza virus continues to serve as a severe threat to human health. It causes serious disease and even death among susceptible populations, as well as direct and indirect economic losses. Traditional vaccine cannot protect humans from a novel outbreak of the influenza virus, such as the H7N9 that occurred in 20134. The anti-influenza broadly neutralizing antibodies found in infected humans have provided new insights into universal influenza vaccine development[12]. Passive immunization of broadly neutralizing antibodies might be the most effective countermeasure for influenza infection. C17914 is the first isolated influenza broadly neutralizing antibody that can neutralize all H1 and H2 strains It can cross-neutralize the H5, H6, and H9 strains[15].
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