Antigenic Change in Human Influenza A(H2N2) Viruses Detected by Using Human Plasma from Aged and Younger Adult Individuals.
Identifieur interne : 000006 ( PubMed/Corpus ); précédent : 000005; suivant : 000007Antigenic Change in Human Influenza A(H2N2) Viruses Detected by Using Human Plasma from Aged and Younger Adult Individuals.
Auteurs : Yukimasa Matsuzawa ; Kiyoko Iwatsuki-Horimoto ; Yoshinori Nishimoto ; Yukiko Abe ; Satoshi Fukuyama ; Taiki Hamabata ; Moe Okuda ; Yui Go ; Tokiko Watanabe ; Masaki Imai ; Yasumichi Arai ; Ron A M. Fouchier ; Seiya Yamayoshi ; Yoshihiro KawaokaSource :
- Viruses [ 1999-4915 ] ; 2019.
Abstract
Human influenza A(H2N2) viruses emerged in 1957 and were replaced by A(H3N2) viruses in 1968. The antigenicity of human H2N2 viruses has been tested by using ferret antisera or mouse and human monoclonal antibodies. Here, we examined the antigenicity of human H2N2 viruses by using human plasma samples obtained from 50 aged individuals who were born between 1928 and 1933 and from 33 younger adult individuals who were born after 1962. The aged individuals possessed higher neutralization titers against H2N2 viruses isolated in 1957 and 1963 than those against H2N2 viruses isolated in 1968, whereas the younger adults who were born between 1962 and 1968 possessed higher neutralization titers against H2N2 viruses isolated in 1963 than those against other H2N2 viruses. Antigenic cartography revealed the antigenic changes that occurred in human H2N2 viruses during circulation in humans for 11 years, as detected by ferret antisera. These results show that even though aged individuals were likely exposed to more recent H2N2 viruses that are antigenically distinct from the earlier H2N2 viruses, they did not possess high neutralizing antibody titers to the more recent viruses, suggesting immunological imprinting of these individuals with the first H2N2 viruses they encountered and that this immunological imprinting lasts for over 50 years.
DOI: 10.3390/v11110978
PubMed: 31652870
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Antigenic Change in Human Influenza A(H2N2) Viruses Detected by Using Human Plasma from Aged and Younger Adult Individuals.</title><author><name sortKey="Matsuzawa, Yukimasa" sort="Matsuzawa, Yukimasa" uniqKey="Matsuzawa Y" first="Yukimasa" last="Matsuzawa">Yukimasa Matsuzawa</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. ymatsuza@ims.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Iwatsuki Horimoto, Kiyoko" sort="Iwatsuki Horimoto, Kiyoko" uniqKey="Iwatsuki Horimoto K" first="Kiyoko" last="Iwatsuki-Horimoto">Kiyoko Iwatsuki-Horimoto</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. kenken@ims.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Nishimoto, Yoshinori" sort="Nishimoto, Yoshinori" uniqKey="Nishimoto Y" first="Yoshinori" last="Nishimoto">Yoshinori Nishimoto</name><affiliation><nlm:affiliation>Center for Supercentenarian Medical Research, Shinjuku-ku, Tokyo 160-8582, Japan. ynishimo@z3.keio.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Abe, Yukiko" sort="Abe, Yukiko" uniqKey="Abe Y" first="Yukiko" last="Abe">Yukiko Abe</name><affiliation><nlm:affiliation>Center for Supercentenarian Medical Research, Shinjuku-ku, Tokyo 160-8582, Japan. yukiko_abe@keio.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Fukuyama, Satoshi" sort="Fukuyama, Satoshi" uniqKey="Fukuyama S" first="Satoshi" last="Fukuyama">Satoshi Fukuyama</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. fukuyamarry@gmail.com.</nlm:affiliation></affiliation></author><author><name sortKey="Hamabata, Taiki" sort="Hamabata, Taiki" uniqKey="Hamabata T" first="Taiki" last="Hamabata">Taiki Hamabata</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. hamabata@ims.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Okuda, Moe" sort="Okuda, Moe" uniqKey="Okuda M" first="Moe" last="Okuda">Moe Okuda</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. kk176356@stu-cbms.k.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Go, Yui" sort="Go, Yui" uniqKey="Go Y" first="Yui" last="Go">Yui Go</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. yuigo555@gmail.com.</nlm:affiliation></affiliation></author><author><name sortKey="Watanabe, Tokiko" sort="Watanabe, Tokiko" uniqKey="Watanabe T" first="Tokiko" last="Watanabe">Tokiko Watanabe</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. tokiko.watanabe@wisc.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Imai, Masaki" sort="Imai, Masaki" uniqKey="Imai M" first="Masaki" last="Imai">Masaki Imai</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. mimai@ims.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Arai, Yasumichi" sort="Arai, Yasumichi" uniqKey="Arai Y" first="Yasumichi" last="Arai">Yasumichi Arai</name><affiliation><nlm:affiliation>Center for Supercentenarian Medical Research, Shinjuku-ku, Tokyo 160-8582, Japan. yasumich@keio.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A M" last="Fouchier">Ron A M. Fouchier</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. r.fouchier@erasmusmc.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Yamayoshi, Seiya" sort="Yamayoshi, Seiya" uniqKey="Yamayoshi S" first="Seiya" last="Yamayoshi">Seiya Yamayoshi</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. yamayo@ims.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. yoshihiro.kawaoka@wisc.edu.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31652870</idno><idno type="pmid">31652870</idno><idno type="doi">10.3390/v11110978</idno><idno type="wicri:Area/PubMed/Corpus">000006</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000006</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Antigenic Change in Human Influenza A(H2N2) Viruses Detected by Using Human Plasma from Aged and Younger Adult Individuals.</title><author><name sortKey="Matsuzawa, Yukimasa" sort="Matsuzawa, Yukimasa" uniqKey="Matsuzawa Y" first="Yukimasa" last="Matsuzawa">Yukimasa Matsuzawa</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. ymatsuza@ims.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Iwatsuki Horimoto, Kiyoko" sort="Iwatsuki Horimoto, Kiyoko" uniqKey="Iwatsuki Horimoto K" first="Kiyoko" last="Iwatsuki-Horimoto">Kiyoko Iwatsuki-Horimoto</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. kenken@ims.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Nishimoto, Yoshinori" sort="Nishimoto, Yoshinori" uniqKey="Nishimoto Y" first="Yoshinori" last="Nishimoto">Yoshinori Nishimoto</name><affiliation><nlm:affiliation>Center for Supercentenarian Medical Research, Shinjuku-ku, Tokyo 160-8582, Japan. ynishimo@z3.keio.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Abe, Yukiko" sort="Abe, Yukiko" uniqKey="Abe Y" first="Yukiko" last="Abe">Yukiko Abe</name><affiliation><nlm:affiliation>Center for Supercentenarian Medical Research, Shinjuku-ku, Tokyo 160-8582, Japan. yukiko_abe@keio.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Fukuyama, Satoshi" sort="Fukuyama, Satoshi" uniqKey="Fukuyama S" first="Satoshi" last="Fukuyama">Satoshi Fukuyama</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. fukuyamarry@gmail.com.</nlm:affiliation></affiliation></author><author><name sortKey="Hamabata, Taiki" sort="Hamabata, Taiki" uniqKey="Hamabata T" first="Taiki" last="Hamabata">Taiki Hamabata</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. hamabata@ims.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Okuda, Moe" sort="Okuda, Moe" uniqKey="Okuda M" first="Moe" last="Okuda">Moe Okuda</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. kk176356@stu-cbms.k.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Go, Yui" sort="Go, Yui" uniqKey="Go Y" first="Yui" last="Go">Yui Go</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. yuigo555@gmail.com.</nlm:affiliation></affiliation></author><author><name sortKey="Watanabe, Tokiko" sort="Watanabe, Tokiko" uniqKey="Watanabe T" first="Tokiko" last="Watanabe">Tokiko Watanabe</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. tokiko.watanabe@wisc.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Imai, Masaki" sort="Imai, Masaki" uniqKey="Imai M" first="Masaki" last="Imai">Masaki Imai</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. mimai@ims.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Arai, Yasumichi" sort="Arai, Yasumichi" uniqKey="Arai Y" first="Yasumichi" last="Arai">Yasumichi Arai</name><affiliation><nlm:affiliation>Center for Supercentenarian Medical Research, Shinjuku-ku, Tokyo 160-8582, Japan. yasumich@keio.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A M" last="Fouchier">Ron A M. Fouchier</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. r.fouchier@erasmusmc.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Yamayoshi, Seiya" sort="Yamayoshi, Seiya" uniqKey="Yamayoshi S" first="Seiya" last="Yamayoshi">Seiya Yamayoshi</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. yamayo@ims.u-tokyo.ac.jp.</nlm:affiliation></affiliation></author><author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. yoshihiro.kawaoka@wisc.edu.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Viruses</title><idno type="eISSN">1999-4915</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Human influenza A(H2N2) viruses emerged in 1957 and were replaced by A(H3N2) viruses in 1968. The antigenicity of human H2N2 viruses has been tested by using ferret antisera or mouse and human monoclonal antibodies. Here, we examined the antigenicity of human H2N2 viruses by using human plasma samples obtained from 50 aged individuals who were born between 1928 and 1933 and from 33 younger adult individuals who were born after 1962. The aged individuals possessed higher neutralization titers against H2N2 viruses isolated in 1957 and 1963 than those against H2N2 viruses isolated in 1968, whereas the younger adults who were born between 1962 and 1968 possessed higher neutralization titers against H2N2 viruses isolated in 1963 than those against other H2N2 viruses. Antigenic cartography revealed the antigenic changes that occurred in human H2N2 viruses during circulation in humans for 11 years, as detected by ferret antisera. These results show that even though aged individuals were likely exposed to more recent H2N2 viruses that are antigenically distinct from the earlier H2N2 viruses, they did not possess high neutralizing antibody titers to the more recent viruses, suggesting immunological imprinting of these individuals with the first H2N2 viruses they encountered and that this immunological imprinting lasts for over 50 years.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">31652870</PMID><DateRevised><Year>2020</Year><Month>01</Month><Day>08</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1999-4915</ISSN><JournalIssue CitedMedium="Internet"><Volume>11</Volume><Issue>11</Issue><PubDate><Year>2019</Year><Month>Oct</Month><Day>23</Day></PubDate></JournalIssue><Title>Viruses</Title><ISOAbbreviation>Viruses</ISOAbbreviation></Journal><ArticleTitle>Antigenic Change in Human Influenza A(H2N2) Viruses Detected by Using Human Plasma from Aged and Younger Adult Individuals.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">E978</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3390/v11110978</ELocationID><Abstract><AbstractText>Human influenza A(H2N2) viruses emerged in 1957 and were replaced by A(H3N2) viruses in 1968. The antigenicity of human H2N2 viruses has been tested by using ferret antisera or mouse and human monoclonal antibodies. Here, we examined the antigenicity of human H2N2 viruses by using human plasma samples obtained from 50 aged individuals who were born between 1928 and 1933 and from 33 younger adult individuals who were born after 1962. The aged individuals possessed higher neutralization titers against H2N2 viruses isolated in 1957 and 1963 than those against H2N2 viruses isolated in 1968, whereas the younger adults who were born between 1962 and 1968 possessed higher neutralization titers against H2N2 viruses isolated in 1963 than those against other H2N2 viruses. Antigenic cartography revealed the antigenic changes that occurred in human H2N2 viruses during circulation in humans for 11 years, as detected by ferret antisera. These results show that even though aged individuals were likely exposed to more recent H2N2 viruses that are antigenically distinct from the earlier H2N2 viruses, they did not possess high neutralizing antibody titers to the more recent viruses, suggesting immunological imprinting of these individuals with the first H2N2 viruses they encountered and that this immunological imprinting lasts for over 50 years.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Matsuzawa</LastName><ForeName>Yukimasa</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. ymatsuza@ims.u-tokyo.ac.jp.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Iwatsuki-Horimoto</LastName><ForeName>Kiyoko</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. kenken@ims.u-tokyo.ac.jp.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nishimoto</LastName><ForeName>Yoshinori</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Center for Supercentenarian Medical Research, Shinjuku-ku, Tokyo 160-8582, Japan. ynishimo@z3.keio.jp.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Abe</LastName><ForeName>Yukiko</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Center for Supercentenarian Medical Research, Shinjuku-ku, Tokyo 160-8582, Japan. yukiko_abe@keio.jp.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fukuyama</LastName><ForeName>Satoshi</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. fukuyamarry@gmail.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hamabata</LastName><ForeName>Taiki</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. hamabata@ims.u-tokyo.ac.jp.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Okuda</LastName><ForeName>Moe</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. kk176356@stu-cbms.k.u-tokyo.ac.jp.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Go</LastName><ForeName>Yui</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. yuigo555@gmail.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Watanabe</LastName><ForeName>Tokiko</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. tokiko.watanabe@wisc.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Imai</LastName><ForeName>Masaki</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. mimai@ims.u-tokyo.ac.jp.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Arai</LastName><ForeName>Yasumichi</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Center for Supercentenarian Medical Research, Shinjuku-ku, Tokyo 160-8582, Japan. yasumich@keio.jp.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fouchier</LastName><ForeName>Ron A M</ForeName><Initials>RAM</Initials><AffiliationInfo><Affiliation>Department of Viroscience, Erasmus Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. r.fouchier@erasmusmc.nl.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yamayoshi</LastName><ForeName>Seiya</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. yamayo@ims.u-tokyo.ac.jp.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kawaoka</LastName><ForeName>Yoshihiro</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. yoshihiro.kawaoka@wisc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Special Pathogens, International Research Center for Infectious Diseases, Institute Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. yoshihiro.kawaoka@wisc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. yoshihiro.kawaoka@wisc.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>JP18am001007</GrantID><Agency>Japan Agency for Medical Research and Development</Agency><Country></Country></Grant><Grant><GrantID>JP19fm0108006</GrantID><Agency>Japan Agency for Medical Research and Development</Agency><Country></Country></Grant><Grant><GrantID>16H06429</GrantID><Agency>Ministry of Education, Culture, Sports, Science and Technology</Agency><Country></Country></Grant><Grant><GrantID>16K21723</GrantID><Agency>Ministry of Education, Culture, Sports, Science and Technology</Agency><Country></Country></Grant><Grant><GrantID>16H06434</GrantID><Agency>Ministry of Education, Culture, Sports, Science and Technology</Agency><Country></Country></Grant><Grant><GrantID>18H03055</GrantID><Agency>Ministry of Education, Culture, Sports, Science and Technology</Agency><Country></Country></Grant><Grant><GrantID>JP19fk0108031</GrantID><Agency>Japan Agency for Medical Research and Development</Agency><Country></Country></Grant><Grant><GrantID>JP19fk0108056</GrantID><Agency>Japan Agency for Medical Research and Development</Agency><Country></Country></Grant><Grant><GrantID>JP19fk010866</GrantID><Agency>Japan Agency for Medical Research and Development</Agency><Country></Country></Grant><Grant><GrantID>JP15667051</GrantID><Agency>Japan Science and Technology Agency</Agency><Country></Country></Grant><Grant><GrantID>HHSN272201400008C</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>10</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Viruses</MedlineTA><NlmUniqueID>101509722</NlmUniqueID><ISSNLinking>1999-4915</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">H2N2</Keyword><Keyword MajorTopicYN="N">aged individuals</Keyword><Keyword MajorTopicYN="N">antigenic change</Keyword><Keyword MajorTopicYN="N">antigenic drift</Keyword><Keyword MajorTopicYN="N">influenza A virus</Keyword></KeywordList><CoiStatement>Y.K. has received speaker’s honoraria from Toyama Chemical and Astellas Inc.; has received grant support from Chugai Pharmaceuticals, Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Inc., Otsuka Pharmaceutical Co., Ltd., and Denka Seiken Co., Ltd.; and is a co-founder of FluGen. Y.Arai. has received a research grant from Daiichi Sankyo Co, Ltd. and Novartis Pharma K K. 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