VSV-Displayed HIV-1 Envelope Identifies Broadly Neutralizing Antibodies Class-Switched to IgG and IgA

Manxue Jia; Rachel A. Liberatore; Yicheng Guo; Kun Wei Chan; Ruimin Pan; Hong Lu; Eric Waltari; Eva Mittler; Kartik Chandran; Andrés Finzi; Daniel E. Kaufmann; Michael S. Seaman; David D. Ho; Lawrence Shapiro; Zizhang Sheng; Xiang Peng Kong; Paul D. Bieniasz; Xueling Wu

doi:10.1016/j.chom.2020.03.024

VSV-Displayed HIV-1 Envelope Identifies Broadly Neutralizing Antibodies Class-Switched to IgG and IgA

Manxue Jia, Rachel A. Liberatore, Yicheng Guo, Kun Wei Chan, Ruimin Pan, Hong Lu, Eric Waltari, Eva Mittler, Kartik Chandran, Andrés Finzi, Daniel E. Kaufmann, Michael S. Seaman, David D. Ho, Lawrence Shapiro, Zizhang Sheng, Xiang Peng Kong, Paul D. Bieniasz, Xueling Wu

Microbiology & Immunology

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

22 Scopus citations

Abstract

The HIV-1 envelope (Env) undergoes conformational changes during infection. Broadly neutralizing antibodies (bNAbs) are typically isolated by using soluble Env trimers, which do not capture all Env states. To address these limitations, we devised a vesicular stomatitis virus (VSV)-based probe to display membrane-embedded Env trimers and isolated five bNAbs from two chronically infected donors, M4008 and M1214. Donor B cell receptor (BCR) repertoires identified two bNAb lineages, M4008_N1 and M1214_N1, that class-switched to immunoglobulin G (IgG) and IgA. Variants of these bNAbs reconstituted as IgA demonstrated broadly neutralizing activity, and the IgA fraction of M1214 plasma conferred neutralization. M4008_N1 epitope mapping revealed a glycan-independent V3 epitope conferring tier 2 virus neutralization. A 4.86-Å-resolution cryogenic electron microscopy (cryo-EM) structure of M1214_N1 complexed with CH505 SOSIP revealed another elongated epitope, the V2V5 corridor, extending from V2 to V5. Overall, the VSV_ENV probe identified bNAb lineages with neutralizing IgG and IgA members targeting distinct sites of HIV-1 Env vulnerability.

Original language	English (US)
Pages (from-to)	963-975.e5
Journal	Cell Host and Microbe
Volume	27
Issue number	6
DOIs	https://doi.org/10.1016/j.chom.2020.03.024
State	Published - Jun 10 2020

Keywords

Env immunogen design
HIV vaccine
IgG to IgA
V2V5 corridor
antibody class-switch
broadly neutralizing antibody
cryo-EM

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chom.2020.03.024

Cite this

Jia, M., Liberatore, R. A., Guo, Y., Chan, K. W., Pan, R., Lu, H., Waltari, E., Mittler, E., Chandran, K., Finzi, A., Kaufmann, D. E., Seaman, M. S., Ho, D. D., Shapiro, L., Sheng, Z., Kong, X. P., Bieniasz, P. D., & Wu, X. (2020). VSV-Displayed HIV-1 Envelope Identifies Broadly Neutralizing Antibodies Class-Switched to IgG and IgA. Cell Host and Microbe, 27(6), 963-975.e5. https://doi.org/10.1016/j.chom.2020.03.024

Jia, M, Liberatore, RA, Guo, Y, Chan, KW, Pan, R, Lu, H, Waltari, E, Mittler, E , Chandran, K, Finzi, A, Kaufmann, DE, Seaman, MS, Ho, DD, Shapiro, L, Sheng, Z, Kong, XP, Bieniasz, PD & Wu, X 2020, 'VSV-Displayed HIV-1 Envelope Identifies Broadly Neutralizing Antibodies Class-Switched to IgG and IgA', Cell Host and Microbe, vol. 27, no. 6, pp. 963-975.e5. https://doi.org/10.1016/j.chom.2020.03.024

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abstract = "The HIV-1 envelope (Env) undergoes conformational changes during infection. Broadly neutralizing antibodies (bNAbs) are typically isolated by using soluble Env trimers, which do not capture all Env states. To address these limitations, we devised a vesicular stomatitis virus (VSV)-based probe to display membrane-embedded Env trimers and isolated five bNAbs from two chronically infected donors, M4008 and M1214. Donor B cell receptor (BCR) repertoires identified two bNAb lineages, M4008_N1 and M1214_N1, that class-switched to immunoglobulin G (IgG) and IgA. Variants of these bNAbs reconstituted as IgA demonstrated broadly neutralizing activity, and the IgA fraction of M1214 plasma conferred neutralization. M4008_N1 epitope mapping revealed a glycan-independent V3 epitope conferring tier 2 virus neutralization. A 4.86-{\AA}-resolution cryogenic electron microscopy (cryo-EM) structure of M1214_N1 complexed with CH505 SOSIP revealed another elongated epitope, the V2V5 corridor, extending from V2 to V5. Overall, the VSVENV probe identified bNAb lineages with neutralizing IgG and IgA members targeting distinct sites of HIV-1 Env vulnerability.",

keywords = "Env immunogen design, HIV vaccine, IgG to IgA, V2V5 corridor, antibody class-switch, broadly neutralizing antibody, cryo-EM",

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T1 - VSV-Displayed HIV-1 Envelope Identifies Broadly Neutralizing Antibodies Class-Switched to IgG and IgA

AU - Jia, Manxue

AU - Liberatore, Rachel A.

AU - Guo, Yicheng

AU - Chan, Kun Wei

AU - Pan, Ruimin

AU - Lu, Hong

AU - Waltari, Eric

AU - Mittler, Eva

AU - Chandran, Kartik

AU - Finzi, Andrés

AU - Kaufmann, Daniel E.

AU - Seaman, Michael S.

AU - Ho, David D.

AU - Shapiro, Lawrence

AU - Sheng, Zizhang

AU - Kong, Xiang Peng

AU - Bieniasz, Paul D.

AU - Wu, Xueling

PY - 2020/6/10

Y1 - 2020/6/10

N2 - The HIV-1 envelope (Env) undergoes conformational changes during infection. Broadly neutralizing antibodies (bNAbs) are typically isolated by using soluble Env trimers, which do not capture all Env states. To address these limitations, we devised a vesicular stomatitis virus (VSV)-based probe to display membrane-embedded Env trimers and isolated five bNAbs from two chronically infected donors, M4008 and M1214. Donor B cell receptor (BCR) repertoires identified two bNAb lineages, M4008_N1 and M1214_N1, that class-switched to immunoglobulin G (IgG) and IgA. Variants of these bNAbs reconstituted as IgA demonstrated broadly neutralizing activity, and the IgA fraction of M1214 plasma conferred neutralization. M4008_N1 epitope mapping revealed a glycan-independent V3 epitope conferring tier 2 virus neutralization. A 4.86-Å-resolution cryogenic electron microscopy (cryo-EM) structure of M1214_N1 complexed with CH505 SOSIP revealed another elongated epitope, the V2V5 corridor, extending from V2 to V5. Overall, the VSVENV probe identified bNAb lineages with neutralizing IgG and IgA members targeting distinct sites of HIV-1 Env vulnerability.

AB - The HIV-1 envelope (Env) undergoes conformational changes during infection. Broadly neutralizing antibodies (bNAbs) are typically isolated by using soluble Env trimers, which do not capture all Env states. To address these limitations, we devised a vesicular stomatitis virus (VSV)-based probe to display membrane-embedded Env trimers and isolated five bNAbs from two chronically infected donors, M4008 and M1214. Donor B cell receptor (BCR) repertoires identified two bNAb lineages, M4008_N1 and M1214_N1, that class-switched to immunoglobulin G (IgG) and IgA. Variants of these bNAbs reconstituted as IgA demonstrated broadly neutralizing activity, and the IgA fraction of M1214 plasma conferred neutralization. M4008_N1 epitope mapping revealed a glycan-independent V3 epitope conferring tier 2 virus neutralization. A 4.86-Å-resolution cryogenic electron microscopy (cryo-EM) structure of M1214_N1 complexed with CH505 SOSIP revealed another elongated epitope, the V2V5 corridor, extending from V2 to V5. Overall, the VSVENV probe identified bNAb lineages with neutralizing IgG and IgA members targeting distinct sites of HIV-1 Env vulnerability.

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KW - HIV vaccine

KW - IgG to IgA

KW - V2V5 corridor

KW - antibody class-switch

KW - broadly neutralizing antibody

KW - cryo-EM

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SN - 1931-3128

VL - 27

SP - 963-975.e5

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 6

ER -

VSV-Displayed HIV-1 Envelope Identifies Broadly Neutralizing Antibodies Class-Switched to IgG and IgA

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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