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
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 -