TY - JOUR
T1 - Implications of a highly divergent dengue virus strain for cross-neutralization, protection, and vaccine immunity
AU - Chen, Rita E.
AU - Smith, Brittany K.
AU - Errico, John M.
AU - Gordon, David N.
AU - Winkler, Emma S.
AU - VanBlargan, Laura A.
AU - Desai, Chandni
AU - Handley, Scott A.
AU - Dowd, Kimberly A.
AU - Amaro-Carambot, Emerito
AU - Cardosa, M. Jane
AU - Sariol, Carlos A.
AU - Kallas, Esper G.
AU - Sékaly, Rafick Pierre
AU - Vasilakis, Nikos
AU - Fremont, Daved H.
AU - Whitehead, Stephen S.
AU - Pierson, Theodore C.
AU - Diamond, Michael S.
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/11/10
Y1 - 2021/11/10
N2 - Although divergent dengue viruses (DENVs) have been isolated in insects, nonhuman primates, and humans, their relationships to the four canonical serotypes (DENV 1–4) are poorly understood. One virus isolated from a dengue patient, DKE-121, falls between genotype and serotype levels of sequence divergence to DENV-4. To examine its antigenic relationship to DENV-4, we assessed serum neutralizing and protective activity. Whereas DENV-4-immune mouse sera neutralize DKE-121 infection, DKE-121-immune sera inhibit DENV-4 less efficiently. Passive transfer of DENV-4 or DKE-121-immune sera protects mice against homologous, but not heterologous, DENV-4 or DKE-121 challenge. Antigenic cartography suggests that DENV-4 and DKE-121 are related but antigenically distinct. However, DENV-4 vaccination confers protection against DKE-121 in nonhuman primates, and serum from humans immunized with a tetravalent vaccine neutralize DENV-4 and DKE-121 infection equivalently. As divergent DENV strains, such as DKE-121, may meet criteria for serotype distinction, monitoring their capacity to impact dengue disease and vaccine efficacy appears warranted.
AB - Although divergent dengue viruses (DENVs) have been isolated in insects, nonhuman primates, and humans, their relationships to the four canonical serotypes (DENV 1–4) are poorly understood. One virus isolated from a dengue patient, DKE-121, falls between genotype and serotype levels of sequence divergence to DENV-4. To examine its antigenic relationship to DENV-4, we assessed serum neutralizing and protective activity. Whereas DENV-4-immune mouse sera neutralize DKE-121 infection, DKE-121-immune sera inhibit DENV-4 less efficiently. Passive transfer of DENV-4 or DKE-121-immune sera protects mice against homologous, but not heterologous, DENV-4 or DKE-121 challenge. Antigenic cartography suggests that DENV-4 and DKE-121 are related but antigenically distinct. However, DENV-4 vaccination confers protection against DKE-121 in nonhuman primates, and serum from humans immunized with a tetravalent vaccine neutralize DENV-4 and DKE-121 infection equivalently. As divergent DENV strains, such as DKE-121, may meet criteria for serotype distinction, monitoring their capacity to impact dengue disease and vaccine efficacy appears warranted.
KW - antibody
KW - dengue
KW - divergent
KW - genotype
KW - neutralization
KW - pathogenesis
KW - protection
KW - serotype
UR - http://www.scopus.com/inward/record.url?scp=85118590461&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2021.09.006
DO - 10.1016/j.chom.2021.09.006
M3 - Article
C2 - 34610295
AN - SCOPUS:85118590461
SN - 1931-3128
VL - 29
SP - 1634-1648.e5
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 11
ER -