Researchers showed that immune pressure on the hemagglutinin (HA) stalk could lead to expansion of escape mutant viruses in study participants challenged with a 2009 H1N1 pandemic influenza virus inoculum containing an A388V polymorphism in the HA stalk
[Nature Medicine]
6445212
{6445212:HE4663J4}
apa
50
1
151213
https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-966ac103a544cedf9665bc03c89956ca%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22HE4663J4%22%2C%22library%22%3A%7B%22id%22%3A6445212%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Park%20et%20al.%22%2C%22parsedDate%22%3A%222020-06-29%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%202em%3B%20text-indent%3A-2em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EPark%2C%20J.-K.%2C%20Xiao%2C%20Y.%2C%20Ramuta%2C%20M.%20D.%2C%20Rosas%2C%20L.%20A.%2C%20Fong%2C%20S.%2C%20Matthews%2C%20A.%20M.%2C%20%26%23x2026%3B%20Taubenberger%2C%20J.%20K.%20%282020%29.%20Pre-existing%20immunity%20to%20influenza%20virus%20hemagglutinin%20stalk%20might%20drive%20selection%20for%20antibody-escape%20mutant%20viruses%20in%20a%20human%20challenge%20model.%20%3Ci%3ENature%20Medicine%3C%5C%2Fi%3E%2C%201%26%23x2013%3B7.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41591-020-0937-x%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41591-020-0937-x%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D6445212%26amp%3Bitem_key%3DHE4663J4%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Pre-existing%20immunity%20to%20influenza%20virus%20hemagglutinin%20stalk%20might%20drive%20selection%20for%20antibody-escape%20mutant%20viruses%20in%20a%20human%20challenge%20model%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jae-Keun%22%2C%22lastName%22%3A%22Park%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yongli%22%2C%22lastName%22%3A%22Xiao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mitchell%20D.%22%2C%22lastName%22%3A%22Ramuta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Luz%20Angela%22%2C%22lastName%22%3A%22Rosas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sharon%22%2C%22lastName%22%3A%22Fong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexis%20M.%22%2C%22lastName%22%3A%22Matthews%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ashley%20D.%22%2C%22lastName%22%3A%22Freeman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Monica%20A.%22%2C%22lastName%22%3A%22Gouzoulis%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Natalia%20A.%22%2C%22lastName%22%3A%22Batchenkova%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xingdong%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kelsey%22%2C%22lastName%22%3A%22Scherler%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Li%22%2C%22lastName%22%3A%22Qi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Susan%22%2C%22lastName%22%3A%22Reed%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rani%22%2C%22lastName%22%3A%22Athota%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lindsay%22%2C%22lastName%22%3A%22Czajkowski%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alison%22%2C%22lastName%22%3A%22Han%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20M.%22%2C%22lastName%22%3A%22Morens%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kathie-Anne%22%2C%22lastName%22%3A%22Walters%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Matthew%20J.%22%2C%22lastName%22%3A%22Memoli%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22John%20C.%22%2C%22lastName%22%3A%22Kash%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jeffery%20K.%22%2C%22lastName%22%3A%22Taubenberger%22%7D%5D%2C%22abstractNote%22%3A%22The%20conserved%20region%20of%20influenza%20hemagglutinin%20%28HA%29%20stalk%20%28or%20stem%29%20has%20gained%20attention%20as%20a%20potent%20target%20for%20universal%20influenza%20vaccines1%5Cu20135.%20Although%20the%20HA%20stalk%20region%20is%20relatively%20well%20conserved%2C%20the%20evolutionarily%20dynamic%20nature%20of%20influenza%20viruses6%20raises%20concerns%20about%20the%20possible%20emergence%20of%20viruses%20carrying%20stalk%20escape%20mutation%28s%29%20under%20sufficient%20immune%20pressure.%20Here%20we%20show%20that%20immune%20pressure%20on%20the%20HA%20stalk%20can%20lead%20to%20expansion%20of%20escape%20mutant%20viruses%20in%20study%20participants%20challenged%20with%20a%202009%20H1N1%20pandemic%20influenza%20virus%20inoculum%20containing%20an%20A388V%20polymorphism%20in%20the%20HA%20stalk%20%2845%25%20wild%20type%20and%2055%25%20mutant%29.%20High%20level%20of%20stalk%20antibody%20titers%20was%20associated%20with%20the%20selection%20of%20the%20mutant%20virus%20both%20in%20humans%20and%20in%20vitro.%20Although%20the%20mutant%20virus%20showed%20slightly%20decreased%20replication%20in%20mice%2C%20it%20was%20not%20observed%20in%20cell%20culture%2C%20ferrets%20or%20human%20challenge%20participants.%20The%20A388V%20mutation%20conferred%20resistance%20to%20some%20of%20the%20potent%20HA%20stalk%20broadly%20neutralizing%20monoclonal%20antibodies%20%28bNAbs%29.%20Co-culture%20of%20wild-type%20and%20mutant%20viruses%20in%20the%20presence%20of%20either%20a%20bNAb%20or%20human%20serum%20resulted%20in%20rapid%20expansion%20of%20the%20mutant.%20These%20data%20shed%20light%20on%20a%20potential%20obstacle%20for%20the%20success%20of%20HA-stalk-targeting%20universal%20influenza%20vaccines%5Cu2014viral%20escape%20from%20vaccine-induced%20stalk%20immunity.%22%2C%22date%22%3A%222020-06-29%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41591-020-0937-x%22%2C%22ISSN%22%3A%221546-170X%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41591-020-0937-x%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222020-06-29T16%3A26%3A46Z%22%7D%7D%5D%7D
Park, J.-K., Xiao, Y., Ramuta, M. D., Rosas, L. A., Fong, S., Matthews, A. M., … Taubenberger, J. K. (2020). Pre-existing immunity to influenza virus hemagglutinin stalk might drive selection for antibody-escape mutant viruses in a human challenge model. Nature Medicine, 1–7. https://doi.org/10.1038/s41591-020-0937-x Cite
