A broadly protective therapeutic antibody against influenza B virus with two mechanisms of action

Ning Chai (), Lee R. Swem, Summer Park, Gerald Nakamura, Nancy Chiang, Alberto Estevez, Rina Fong, Lynn Kamen, Elviza Kho, Mike Reichelt, Zhonghua Lin, Henry Chiu, Elizabeth Skippington, Zora Modrusan, Jeremy Stinson, Min Xu, Patrick Lupardus, Claudio Ciferri and Man-Wah Tan ()
Additional contact information
Ning Chai: Genentech
Lee R. Swem: Genentech
Summer Park: Genentech
Gerald Nakamura: Genentech
Nancy Chiang: Genentech
Alberto Estevez: Genentech
Rina Fong: Genentech
Lynn Kamen: Genentech
Elviza Kho: Genentech
Mike Reichelt: Genentech
Zhonghua Lin: Genentech
Henry Chiu: Genentech
Elizabeth Skippington: Genentech
Zora Modrusan: Genentech
Jeremy Stinson: Genentech
Min Xu: Genentech
Patrick Lupardus: Genentech
Claudio Ciferri: Genentech
Man-Wah Tan: Genentech

Nature Communications, 2017, vol. 8, issue 1, 1-18

Abstract: Abstract Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion. After passage of the B/Brisbane/60/2008 virus in the presence of 46B8, we isolated three resistant clones, all harbouring the same mutation (Ser301Phe) in HA that abolishes 46B8 binding to HA at low pH. Interestingly, 46B8 is still able to protect mice against lethal challenge of the mutant viruses, possibly owing to its ability to mediate antibody-dependent cellular cytotoxicity (ADCC).

Date: 2017
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DOI: 10.1038/ncomms14234

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