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Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody

Esswein, Shannon R. ; Gristick, Harry B. ; Jurado, Andrea ; Peace, Avery ; Keeffe, Jennifer R. ; Lee, Yu E. ; Voll, Alisa V. ; Saeed, Mohsan ; Nussenzweig, Michel C. ; Rice, Charles M. ; Robbiani, Davide F. ; MacDonald, Margaret R. ; Bjorkman, Pamela J.

Proceedings of the National Academy of Sciences - PNAS, 2020-05, Vol.117 (18), p.9865-9875 [Peer Reviewed Journal]

United States: National Academy of Sciences

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Title:
Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody
Author: Esswein, Shannon R. ; Gristick, Harry B. ; Jurado, Andrea ; Peace, Avery ; Keeffe, Jennifer R. ; Lee, Yu E. ; Voll, Alisa V. ; Saeed, Mohsan ; Nussenzweig, Michel C. ; Rice, Charles M. ; Robbiani, Davide F. ; MacDonald, Margaret R. ; Bjorkman, Pamela J.
Subjects: Abnormalities ; Affinity ; affinity maturation ; Animals ; Antibodies ; Antibodies, Monoclonal - immunology ; Antibodies, Neutralizing - immunology ; Antibodies, Neutralizing - isolation & purification ; Antibodies, Viral - immunology ; Antibody response ; antibody-dependent enhancement ; BASIC BIOLOGICAL SCIENCES ; Binding ; Biological Sciences ; Cross-reactivity ; Dengue fever ; Dengue Virus - immunology ; Dengue Virus - pathogenicity ; Epidemics ; Epitopes - immunology ; Flaviviridae ; flavivirus ; Germ Cells - immunology ; germline antibody ; Humans ; Infant, Newborn ; Infections ; Maturation ; Microencephaly ; Mosquitoes ; Neonates ; Neurodevelopmental disorders ; Neutralizing ; Prophylaxis ; Protein Domains - immunology ; Proteins ; Vaccines ; Vector-borne diseases ; Viral envelope proteins ; Viral Envelope Proteins - immunology ; Viral Vaccines - immunology ; Viruses ; West Nile virus ; West Nile virus - immunology ; West Nile virus - pathogenicity ; Yellow fever virus - immunology ; Yellow fever virus - pathogenicity ; Zika ; Zika virus ; Zika Virus - immunology ; Zika Virus - isolation & purification ; Zika Virus Infection - diagnosis ; Zika Virus Infection - immunology ; Zika Virus Infection - virology
Is Part Of: Proceedings of the National Academy of Sciences - PNAS, 2020-05, Vol.117 (18), p.9865-9875
Notes: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Sanofi-Aventis Bioengineering Research Program
P01AI138938; 5-T32-GM007616-40; F30AI147579; T32-GM008042
USDOE Office of Science (SC), Basic Energy Sciences (BES)
National Institutes of Health (NIH)
Beckman Institute
Gordon and Betty Moore Foundation
National Institute of General Medical Sciences (NIGMS)
1Present address: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118.
2Present address: National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118.
Author contributions: S.R.E., J.R.K., M.R.M., and P.J.B. designed research; S.R.E., H.B.G., A.J., A.P., Y.E.L., and A.V.V. performed research; S.R.E., Y.E.L., M.S., M.C.N., C.M.R., and D.F.R. contributed new reagents/analytic tools; S.R.E., J.R.K., D.F.R., M.R.M., and P.J.B. analyzed data; and S.R.E. and P.J.B. wrote the paper.
Edited by Stephen C. Harrison, Boston Children’s Hospital, Boston, MA, and approved March 23, 2020 (received for review November 3, 2019)
Description: Recent epidemics demonstrate the global threat of Zika virus (ZIKV), a flavivirus transmitted by mosquitoes. Although infection is usually asymptomatic or mild, newborns of infected mothers can display severe symptoms, including neurodevelopmental abnormalities and microcephaly. Given the large-scale spread, symptom severity, and lack of treatment or prophylaxis, a safe and effective ZIKV vaccine is urgently needed. However, vaccine design is complicated by concern that elicited antibodies (Abs) may cross-react with other flaviviruses that share a similar envelope protein, such as dengue virus, West Nile virus, and yellow fever virus. This cross-reactivity may worsen symptoms of a subsequent infection through Ab-dependent enhancement. To better understand the neutralizing Ab response and risk of Ab-dependent enhancement, further information on germline Ab binding to ZIKV and the maturation process that gives rise to potently neutralizing Abs is needed. Here we use binding and structural studies to compare mature and inferred-germline Ab binding to envelope protein domain III of ZIKV and other flaviviruses. We show that affinity maturation of the light-chain variable domain is important for strong binding of the recurrent VH3-23/VK1-5 neutralizing Abs to ZIKV envelope protein domain III, and identify interacting residues that contribute to weak, cross-reactive binding to West Nile virus. These findings provide insight into the affinity maturation process and potential cross-reactivity of VH3-23/VK1-5 neutralizing Abs, informing precautions for protein-based vaccines designed to elicit germline versions of neutralizing Abs.
Publisher: United States: National Academy of Sciences
Language: English;Chinese

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Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody

Esswein, Shannon R. ; Gristick, Harry B. ; Jurado, Andrea ; Peace, Avery ; Keeffe, Jennifer R. ; Lee, Yu E. ; Voll, Alisa V. ; Saeed, Mohsan ; Nussenzweig, Michel C. ; Rice, Charles M. ; Robbiani, Davide F. ; MacDonald, Margaret R. ; Bjorkman, Pamela J.

United States: National Academy of Sciences

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