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Therapeutic administration of broadly neutralizing FI6 antibody reveals lack of interaction between human IgG1 and pig Fc receptors

Morgan, S, Holzer, B, Hemmink, J, Salguero Bodes, Francisco, Schwartz, J, Agatic, G, Cameroni, E, Guarino, B, Porter, E, Rijal, P , Townsend, A, Charleston, B, Corti, D and Tchilian, E (2018) Therapeutic administration of broadly neutralizing FI6 antibody reveals lack of interaction between human IgG1 and pig Fc receptors Frontiers in Immunology, 9, 865.

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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 in pigs with cross-reactive non-neutralising 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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
Morgan, S
Holzer, B
Hemmink, J
Salguero Bodes,
Schwartz, J
Agatic, G
Cameroni, E
Guarino, B
Porter, E
Rijal, P
Townsend, A
Charleston, B
Corti, D
Tchilian, E
Date : 24 April 2018
Funders : BBSRC
DOI : 10.3389/fimmu.2018.00865
Copyright Disclaimer : © 2018 Morgan, Holzer, Hemmink, Salguero, Schwartz, Agatic, Cameroni, Guarino, Porter, Rijal, Townsend, Charleston, Corti and Tchilian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Uncontrolled Keywords : Influenza1, Anti-stem antibody2, PIG3, Fc receptor4, FI65, Enhanced disease6
Depositing User : Melanie Hughes
Date Deposited : 10 Apr 2018 10:53
Last Modified : 11 Dec 2018 11:24

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