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 - Funding Information:
We thank Leran Wang, Ahmed Hassan, Arthur Kim, Michelle Elam-Noll, and Larissa Thackray for sequence submission, reagents, animal breeding, and experimental suggestions. We acknowledge Aravinda de Silva for providing human serum samples and manuscript comments. We thank Lindsay Droit for help with the generation of viral sequence libraries. This work was supported by NIAID contract 75N93019C00062 and NIH grants R01 AI073755, R01 AI125202, R21 AI145012, and U01 AI115577; a pilot grant by the Institute for Human Infection and Immunity (to N.V.); and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (T.C.P. and S.S.W.). This work was also supported by the Caribbean Primate Research Center (grants P40 OD012217 and U42 OD021458 from ORIP/OD/NIH). E.S.W. is supported by T32 AI007163. R.E.C. generated mouse immune sera, performed FRNT analyses, executed passive transfer mouse experiments, and performed all viral RNA burden analyses. B.K.S. generated antigenic cartography maps. R.E.C. and E.S.W. performed sequential infection mouse experiments. J.M.E. generated alignment figure. D.G. and K.A.D. performed RVP assays. R.E.C. and L.A.V. designed DKE-121 RVP. S.S.W. and E.A.C. performed plaque assays. M.J.C. isolated DKE-121 from patient sera. C.D. L.D. and S.A.H. performed RNA deep-sequencing and analysis. The NHP experiments were designed and executed under the supervision of C.A.S. N.V. or S.S.W. Human sera were provided by E.G.K. R.P.S. and S.S.W. N.V. provided DKE-121 virus. R.E.C. and M.S.D. wrote the initial draft, with the other authors providing editorial comments. M.S.D. is a consultant for Inbios, Vir Biotechnology, and Carnival Corporation and is on the scientific advisory boards of Moderna and Immunome. The Diamond Laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. The Vasilakis laboratory has received unrelated funding support in sponsored research agreements from Public Health Vaccines.
Funding Information:
We thank Leran Wang, Ahmed Hassan, Arthur Kim, Michelle Elam-Noll, and Larissa Thackray for sequence submission, reagents, animal breeding, and experimental suggestions. We acknowledge Aravinda de Silva for providing human serum samples and manuscript comments. We thank Lindsay Droit for help with the generation of viral sequence libraries. This work was supported by NIAID contract 75N93019C00062 and NIH grants R01 AI073755 , R01 AI125202 , R21 AI145012 , and U01 AI115577 ; a pilot grant by the Institute for Human Infection and Immunity (to N.V.); and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (T.C.P. and S.S.W.). This work was also supported by the Caribbean Primate Research Center (grants P40 OD012217 and U42 OD021458 from ORIP / OD / NIH ). E.S.W. is supported by T32 AI007163 .
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 -