Abstract
Influenza virus infection is a significant global health threat. Because of the lack of cross-protective universal vaccines, short time window during which antivirals are effective and drug resistance, new therapeutic anti-influenza strategies are required. Broadly, cross-protective antibodies that target conserved sites in the hemagglutinin (HA) stem region have been proposed as therapeutic agents. FI6 is the first proven such monoclonal antibody to bind to H1–H16 and is protective in mice and ferrets. Multiple studies have shown that Fc-dependent mechanisms are essential for FI6 in vivo efficacy. Here, we show that therapeutic administration of FI6 either intravenously or by aerosol to pigs did not reduce viral load in nasal swabs or broncho-alveolar lavage, but aerosol delivery of FI6 reduced gross pathology significantly. We demonstrate that pig Fc receptors do not bind human IgG1 and that FI6 did not mediate antibody-dependent cytotoxicity (ADCC) with pig PBMC, confirming that ADCC is an important mechanism of protection by anti-stem antibodies in vivo. Enhanced respiratory disease, which has been associated with pigs with cross-reactive non-neutralizing anti-HA antibodies, did not occur after FI6 administration. Our results also show that in vitro neutralizing antibody responses are not a robust correlate of protection for the control of influenza infection and pathology in a natural host model.
Highlights
Influenza virus infection and immunization induce protective antibody responses
In order to determine the therapeutic effect of FI6 antibody in the pig influenza model, FI6 was administered I.V. at 15 mg/kg 1 dpi
We administered FI6 as an aerosol as this route of delivery is highly efficient in targeting the respiratory tract, which is the site of entry and infection of influenza A viruses (IAVs) [20, 24,25,26,27,28]
Summary
Influenza virus infection and immunization induce protective antibody responses. A major part of the antibody response is directed at the hemagglutinin (HA) glycoprotein. Influenza HA is composed of two domains: the immunodominant globular head, which is strain-specific and the stalk which is relatively conserved within each subtype. Seasonal immunization induces antibodies predominantly against the globular head which neutralizes the immunizing strain very effectively, but escape variants rapidly emerge and are responsible for antigenic drift. Influenza-neutralizing antibodies that target conserved sites in the HA stem of influenza A viruses (IAVs) have been described and these show cross-reactivity between group 1 and 2 viruses [1,2,3,4,5,6,7].
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.
