@article{acfff7884d4347639a1b277245a34102,
title = "Antigenic change in human influenza a(H2N2) viruses detected by using human plasma from aged and younger adult individuals",
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.",
keywords = "Aged individuals, Antigenic change, Antigenic drift, H2N2, Influenza A virus",
author = "Yukimasa Matsuzawa and Kiyoko Iwatsuki-Horimoto and Yoshinori Nishimoto and Yukiko Abe and Satoshi Fukuyama and Taiki Hamabata and Moe Okuda and Yui Go and Tokiko Watanabe and Masaki Imai and Yasumichi Arai and Fouchier, {Ron A.M.} and Seiya Yamayoshi and Yoshihiro Kawaoka",
note = "Funding Information: Funding: This research was supported by Leading Advanced Projects for medical innovation (LEAP) from the Japan Agency for Medical Research and Development (AMED) (JP18am001007), by Grants-in-Aid for Scientific Research on Innovativea Areas from the Ministry of Education, Culture, Science, Sports, and Technology (MEXT) Amino acids that are different among the HAs of the four isolates at previously identified antigenic determinants [11] of Japan (Nos. 16H06429, 16K21723, and 16H06434), by Grant-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science (JSPS) (18H03055), by the Japan Initiative for Global Research Network on Although some of the aged individuals likely have been infected with or exposed to later H2N2 viruses, almost of all of the aged individuals maintained high neutralization titers against the H2N2 viruses that caused the pandemic or its antigenically closely related viruses, but possessed low Diseases/NIH contract no. HHSN272201400008C. neutralization titers against later H2N2 viruses. These data suggest that immunological imprinting toward the pandemic H2N2 virus occurred. This would also mean that the immunological imprinting was maintained for 50 years. Antigenic cartography is usually performed by using antisera obtained from ferrets infected wreictheivaendignrfalunte snuzpapvoirrtu frso[m13 C].huIngatih Pishasrtmudacye,uwtiecaulss,e Ddahiiuchmi Saannkpylaos Pmhaarsmaamcepulteiscaol,b Ttaoyinaemda fCrohmemaicgael,d Taanunds younger adults for the antigenic cartography of human H2N2 viruses. Previous studies showed that human infant sera and ferret antisera see the antigenicity of H1N1 and H3N2 viruses differently [14,15]. However, the positions of four H2N2 viruses in the antigenic map we made with the human plasma samples were similar to those obtained with ferret antisera (Figure 3 and ref [11]). This variation in findings with respect to the antigenic differences recognized by human sera/plasma and ferret antisera between H2N2 and H1N1 or H3N2 is interesting and deserves further study. Funding Information: Funding: This research was supported by Leading Advanced Projects for medical innovation (LEAP) from the Japan Agency for Medical Research and Development (AMED) (JP18am001007), by Grants-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Science, Sports, and Technology (MEXT) of Japan (Nos. 16H06429, 16K21723, and 16H06434), by Grant-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science (JSPS) (18H03055), by the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) from AMED (JP19fm0108006), by a Research Program on Emerging and Re-emerging Infectious Diseases from AMED (JP19fk0108031, JP19fk0108056 and JP19fk0108066), and by JST Research Complex Program (JP15667051). R.F. is supported by National Institute of Allergy and Infectious Diseases/NIH contract no. HHSN272201400008C. Publisher Copyright: {\textcopyright} 2019 by the authors.",
year = "2019",
month = oct,
day = "23",
doi = "10.3390/v11110978",
language = "English",
volume = "11",
journal = "Viruses",
issn = "1999-4915",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "11",
}