Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

Rajeshwer S. Sankhala; Vincent Dussupt; Gina Donofrio; Gregory D. Gromowski; Rafael A. De La Barrera; Rafael A. Larocca; Letzibeth Mendez-Rivera; Anna Lee; Misook Choe; Weam Zaky; Grace Mantus; Jaime L. Jensen; Wei Hung Chen; Neelakshi Gohain; Hongjun Bai; Michael K. McCracken; Rosemarie D. Mason; David Leggat; Bonnie M. Slike; Ursula Tran; Ningbo Jian; Peter Abbink; Rebecca Peterson; Eric Araujo Mendes; Rafael Freitas de Oliveira Franca; Guilherme Amaral Calvet; Ana Maria Bispo de Filippis; Adrian McDermott; Mario Roederer; Mayda Hernandez; Amie Albertus; Edgar Davidson; Benjamin J. Doranz; Morgane Rolland; Merlin L. Robb; Rebecca M. Lynch; Dan H. Barouch; Richard G. Jarman; Stephen J. Thomas; Kayvon Modjarrad; Nelson L. Michael; Shelly J. Krebs; M. Gordon Joyce

doi:10.1016/j.celrep.2023.112942

Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

Rajeshwer S. Sankhala, Vincent Dussupt, Gina Donofrio, Gregory D. Gromowski, Rafael A. De La Barrera, Rafael A. Larocca, Letzibeth Mendez-Rivera, Anna Lee, Misook Choe, Weam Zaky, Grace Mantus, Jaime L. Jensen, Wei Hung Chen, Neelakshi Gohain, Hongjun Bai, Michael K. McCracken, Rosemarie D. Mason, David Leggat, Bonnie M. Slike, Ursula TranNingbo Jian, Peter Abbink, Rebecca Peterson, Eric Araujo Mendes, Rafael Freitas de Oliveira Franca, Guilherme Amaral Calvet, Ana Maria Bispo de Filippis, Adrian McDermott, Mario Roederer, Mayda Hernandez, Amie Albertus, Edgar Davidson, Benjamin J. Doranz, Morgane Rolland, Merlin L. Robb, Rebecca M. Lynch, Dan H. Barouch, Richard G. Jarman, Stephen J. Thomas, Kayvon Modjarrad, Nelson L. Michael, Shelly J. Krebs^*, M. Gordon Joyce^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.

Original language	English
Article number	112942
Journal	Cell Reports
Volume	42
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2023.112942
State	Published - 29 Aug 2023
Externally published	Yes

Keywords

CP: Immunology
X-ray crystallography
Zika virus
dengue virus
flavivirus
monoclonal antibodies
neutralizing antibodies
rhesus macaque
structural biology

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10.1016/j.celrep.2023.112942

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Sankhala, R. S., Dussupt, V., Donofrio, G., Gromowski, G. D., De La Barrera, R. A., Larocca, R. A., Mendez-Rivera, L., Lee, A., Choe, M., Zaky, W., Mantus, G., Jensen, J. L., Chen, W. H., Gohain, N., Bai, H., McCracken, M. K., Mason, R. D., Leggat, D., Slike, B. M., ... Joyce, M. G. (2023). Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes. Cell Reports, 42(8), Article 112942. https://doi.org/10.1016/j.celrep.2023.112942

@article{ada5795b9b24452ea0be366b33731361,

title = "Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes",

abstract = "Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.",

keywords = "CP: Immunology, X-ray crystallography, Zika virus, dengue virus, flavivirus, monoclonal antibodies, neutralizing antibodies, rhesus macaque, structural biology",

author = "Sankhala, {Rajeshwer S.} and Vincent Dussupt and Gina Donofrio and Gromowski, {Gregory D.} and {De La Barrera}, {Rafael A.} and Larocca, {Rafael A.} and Letzibeth Mendez-Rivera and Anna Lee and Misook Choe and Weam Zaky and Grace Mantus and Jensen, {Jaime L.} and Chen, {Wei Hung} and Neelakshi Gohain and Hongjun Bai and McCracken, {Michael K.} and Mason, {Rosemarie D.} and David Leggat and Slike, {Bonnie M.} and Ursula Tran and Ningbo Jian and Peter Abbink and Rebecca Peterson and Mendes, {Eric Araujo} and {Freitas de Oliveira Franca}, Rafael and Calvet, {Guilherme Amaral} and {Bispo de Filippis}, {Ana Maria} and Adrian McDermott and Mario Roederer and Mayda Hernandez and Amie Albertus and Edgar Davidson and Doranz, {Benjamin J.} and Morgane Rolland and Robb, {Merlin L.} and Lynch, {Rebecca M.} and Barouch, {Dan H.} and Jarman, {Richard G.} and Thomas, {Stephen J.} and Kayvon Modjarrad and Michael, {Nelson L.} and Krebs, {Shelly J.} and Joyce, {M. Gordon}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = aug,

day = "29",

doi = "10.1016/j.celrep.2023.112942",

language = "English",

volume = "42",

journal = "Cell Reports",

issn = "2211-1247",

number = "8",

}

Sankhala, RS, Dussupt, V, Donofrio, G, Gromowski, GD, De La Barrera, RA, Larocca, RA, Mendez-Rivera, L, Lee, A, Choe, M, Zaky, W, Mantus, G, Jensen, JL, Chen, WH, Gohain, N, Bai, H, McCracken, MK, Mason, RD, Leggat, D, Slike, BM, Tran, U, Jian, N, Abbink, P, Peterson, R, Mendes, EA, Freitas de Oliveira Franca, R, Calvet, GA, Bispo de Filippis, AM, McDermott, A, Roederer, M, Hernandez, M, Albertus, A, Davidson, E, Doranz, BJ, Rolland, M, Robb, ML, Lynch, RM, Barouch, DH, Jarman, RG, Thomas, SJ, Modjarrad, K, Michael, NL, Krebs, SJ & Joyce, MG 2023, 'Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes', Cell Reports, vol. 42, no. 8, 112942. https://doi.org/10.1016/j.celrep.2023.112942

TY - JOUR

T1 - Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

AU - Sankhala, Rajeshwer S.

AU - Dussupt, Vincent

AU - Donofrio, Gina

AU - Gromowski, Gregory D.

AU - De La Barrera, Rafael A.

AU - Larocca, Rafael A.

AU - Mendez-Rivera, Letzibeth

AU - Lee, Anna

AU - Choe, Misook

AU - Zaky, Weam

AU - Mantus, Grace

AU - Jensen, Jaime L.

AU - Chen, Wei Hung

AU - Gohain, Neelakshi

AU - Bai, Hongjun

AU - McCracken, Michael K.

AU - Mason, Rosemarie D.

AU - Leggat, David

AU - Slike, Bonnie M.

AU - Tran, Ursula

AU - Jian, Ningbo

AU - Abbink, Peter

AU - Peterson, Rebecca

AU - Mendes, Eric Araujo

AU - Freitas de Oliveira Franca, Rafael

AU - Calvet, Guilherme Amaral

AU - Bispo de Filippis, Ana Maria

AU - McDermott, Adrian

AU - Roederer, Mario

AU - Hernandez, Mayda

AU - Albertus, Amie

AU - Davidson, Edgar

AU - Doranz, Benjamin J.

AU - Rolland, Morgane

AU - Robb, Merlin L.

AU - Lynch, Rebecca M.

AU - Barouch, Dan H.

AU - Jarman, Richard G.

AU - Thomas, Stephen J.

AU - Modjarrad, Kayvon

AU - Michael, Nelson L.

AU - Krebs, Shelly J.

AU - Joyce, M. Gordon

PY - 2023/8/29

Y1 - 2023/8/29

N2 - Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.

AB - Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.

KW - CP: Immunology

KW - X-ray crystallography

KW - Zika virus

KW - dengue virus

KW - flavivirus

KW - monoclonal antibodies

KW - neutralizing antibodies

KW - rhesus macaque

KW - structural biology

UR - http://www.scopus.com/inward/record.url?scp=85166938135&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2023.112942

DO - 10.1016/j.celrep.2023.112942

M3 - Article

C2 - 37561630

AN - SCOPUS:85166938135

SN - 2211-1247

VL - 42

JO - Cell Reports

JF - Cell Reports

IS - 8

M1 - 112942

ER -

Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

Abstract

Keywords

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