TY - JOUR
T1 - Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies
AU - Adachi, Yu
AU - Tonouchi, Keisuke
AU - Nithichanon, Arnone
AU - Kuraoka, Masayuki
AU - Watanabe, Akiko
AU - Shinnakasu, Ryo
AU - Asanuma, Hideki
AU - Ainai, Akira
AU - Ohmi, Yusuke
AU - Yamamoto, Takuya
AU - Ishii, Ken J.
AU - Hasegawa, Hideki
AU - Takeyama, Haruko
AU - Lertmemongkolchai, Ganjana
AU - Kurosaki, Tomohiro
AU - Ato, Manabu
AU - Kelsoe, Garnett
AU - Takahashi, Yoshimasa
N1 - Funding Information:
We thank Drs. Stephen C. Harrison and Aaron G. Schmidt (Harvard Medical School) for providing HA proteins, Dr. Shu Yulong (WHOCC at China CDC) for providing H7N9 virus strain, and the Japanese Red Cross Society for providing donated blood based on the “Guidelines on the use of donated blood in R&D, etc”. We also thank Ms. E. Izumiyama for technical assistance. This research was supported from the Ministry of Education, Culture, Sports, Science, and Technology in Japan under JP16K19167 (to Y. A.) and JP16K15296 (to Y.T.), from AMED under JP18fk0108051 (to Y.T.). and from the Post-doctoral Program from Research Affairs and Graduate School, Khon Kaen University under 59260 (to A.N.).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Germinal center (GC) B cells at viral replication sites acquire specificity to poorly immunogenic but conserved influenza hemagglutinin (HA) epitopes. Here, high-throughput epitope mapping of local GC B cells is used to identify conserved HA epitope selecting cross-reactive antibodies that mediate heterosubtypic protection. A distinct feature of this epitope is an occlusion in the naive trimeric HA structure that is exposed in the post-fusion HA structure to occur under low pH conditions during viral replication. Importantly, systemic immunization by the post-fusion HA antigen results in GC B cells targeting the occluded epitope, and induces a class of protective antibodies that have cross-group specificity and afford protection independent of virus neutralization activity. Furthermore, this class of broadly protective antibodies develops at late time points and persists. Our results identify a class of cross-protective antibodies that are selected at the viral replication site, and provide insights into vaccine strategies using the occluded epitope.
AB - Germinal center (GC) B cells at viral replication sites acquire specificity to poorly immunogenic but conserved influenza hemagglutinin (HA) epitopes. Here, high-throughput epitope mapping of local GC B cells is used to identify conserved HA epitope selecting cross-reactive antibodies that mediate heterosubtypic protection. A distinct feature of this epitope is an occlusion in the naive trimeric HA structure that is exposed in the post-fusion HA structure to occur under low pH conditions during viral replication. Importantly, systemic immunization by the post-fusion HA antigen results in GC B cells targeting the occluded epitope, and induces a class of protective antibodies that have cross-group specificity and afford protection independent of virus neutralization activity. Furthermore, this class of broadly protective antibodies develops at late time points and persists. Our results identify a class of cross-protective antibodies that are selected at the viral replication site, and provide insights into vaccine strategies using the occluded epitope.
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U2 - 10.1038/s41467-019-11821-6
DO - 10.1038/s41467-019-11821-6
M3 - Article
C2 - 31462639
AN - SCOPUS:85071370639
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3883
ER -