Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates

Isabela Silva de Castro; Giacomo Gorini; Rosemarie Mason; Jason Gorman; Massimiliano Bissa; Mohammad A. Rahman; Anush Arakelyan; Irene Kalisz; Stephen Whitney; Manuel Becerra-Flores; Eric Ni; Kristina Peachman; Hung V. Trinh; Michael Read; Mei Hue Liu; Donald Van Ryk; Dominic Paquin-Proulx; Zhanna Shubin; Marina Tuyishime; Jennifer Peele; Mohammed S. Ahmadi; Raffaello Verardi; Juliane Hill; Margaret Beddall; Richard Nguyen; James D. Stamos; Dai Fujikawa; Susie Min; Luca Schifanella; Monica Vaccari; Veronica Galli; Melvin N. Doster; Namal P.M. Liyanage; Sarkis Sarkis; Francesca Caccuri; Celia LaBranche; David C. Montefiori; Georgia D. Tomaras; Xiaoying Shen; Margherita Rosati; Barbara K. Felber; George N. Pavlakis; David J. Venzon; William Magnanelli; Matthew Breed; Josh Kramer; Brandon F. Keele; Michael A. Eller; Claudia Cicala; James Arthos; Guido Ferrari; Leonid Margolis; Marjorie Robert-Guroff; Peter D. Kwong; Mario Roederer; Mangala Rao; Timothy J. Cardozo; Genoveffa Franchini

doi:10.1016/j.isci.2021.102047

Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates

Isabela Silva de Castro, Giacomo Gorini, Rosemarie Mason, Jason Gorman, Massimiliano Bissa, Mohammad A. Rahman, Anush Arakelyan, Irene Kalisz, Stephen Whitney, Manuel Becerra-Flores, Eric Ni, Kristina Peachman, Hung V. Trinh, Michael Read, Mei Hue Liu, Donald Van Ryk, Dominic Paquin-Proulx, Zhanna Shubin, Marina Tuyishime, Jennifer PeeleMohammed S. Ahmadi, Raffaello Verardi, Juliane Hill, Margaret Beddall, Richard Nguyen, James D. Stamos, Dai Fujikawa, Susie Min, Luca Schifanella, Monica Vaccari, Veronica Galli, Melvin N. Doster, Namal P.M. Liyanage, Sarkis Sarkis, Francesca Caccuri, Celia LaBranche, David C. Montefiori, Georgia D. Tomaras, Xiaoying Shen, Margherita Rosati, Barbara K. Felber, George N. Pavlakis, David J. Venzon, William Magnanelli, Matthew Breed, Josh Kramer, Brandon F. Keele, Michael A. Eller, Claudia Cicala, James Arthos, Guido Ferrari, Leonid Margolis, Marjorie Robert-Guroff, Peter D. Kwong, Mario Roederer, Mangala Rao, Timothy J. Cardozo, Genoveffa Franchini

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Abstract

The efficacy of ALVAC-based HIV and SIV vaccines in humans and macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced antibodies to SIV variable region 1 (V1) inhibit anti-V2 antibody-mediated cytotoxicity and reverse their ability to block V2 peptide interaction with the α₄β₇ integrin. SIV vaccines engineered to delete V1 and favor an α helix, rather than a β sheet V2 conformation, induced V2-specific ADCC correlating with decreased risk of SIV acquisition. Removal of V1 from the HIV-1 clade A/E A244 envelope resulted in decreased binding to antibodies recognizing V2 in the β sheet conformation. Thus, deletion of V1 in HIV envelope immunogens may improve antibody responses to V2 virus vulnerability sites and increase the efficacy of HIV vaccine candidates.

Original language	English (US)
Article number	102047
Journal	iScience
Volume	24
Issue number	2
DOIs	https://doi.org/10.1016/j.isci.2021.102047
State	Published - Feb 19 2021

Bibliographical note

Publisher Copyright:
© 2021

Keywords

Immunology
molecular structure
virology

UN SDGs

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

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Silva de Castro, I., Gorini, G., Mason, R., Gorman, J., Bissa, M., Rahman, M. A., Arakelyan, A., Kalisz, I., Whitney, S., Becerra-Flores, M., Ni, E., Peachman, K., Trinh, H. V., Read, M., Liu, M. H., Van Ryk, D., Paquin-Proulx, D., Shubin, Z., Tuyishime, M., ... Franchini, G. (2021). Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates. iScience, 24(2), Article 102047. https://doi.org/10.1016/j.isci.2021.102047

Silva de Castro, I, Gorini, G, Mason, R, Gorman, J, Bissa, M, Rahman, MA, Arakelyan, A, Kalisz, I, Whitney, S, Becerra-Flores, M, Ni, E, Peachman, K, Trinh, HV, Read, M, Liu, MH, Van Ryk, D, Paquin-Proulx, D, Shubin, Z, Tuyishime, M, Peele, J, Ahmadi, MS, Verardi, R, Hill, J, Beddall, M, Nguyen, R, Stamos, JD, Fujikawa, D, Min, S, Schifanella, L, Vaccari, M, Galli, V, Doster, MN, Liyanage, NPM, Sarkis, S, Caccuri, F, LaBranche, C, Montefiori, DC, Tomaras, GD, Shen, X, Rosati, M, Felber, BK, Pavlakis, GN, Venzon, DJ, Magnanelli, W, Breed, M, Kramer, J, Keele, BF, Eller, MA, Cicala, C, Arthos, J, Ferrari, G, Margolis, L, Robert-Guroff, M, Kwong, PD, Roederer, M, Rao, M, Cardozo, TJ & Franchini, G 2021, 'Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates', iScience, vol. 24, no. 2, 102047. https://doi.org/10.1016/j.isci.2021.102047

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abstract = "The efficacy of ALVAC-based HIV and SIV vaccines in humans and macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced antibodies to SIV variable region 1 (V1) inhibit anti-V2 antibody-mediated cytotoxicity and reverse their ability to block V2 peptide interaction with the α4β7 integrin. SIV vaccines engineered to delete V1 and favor an α helix, rather than a β sheet V2 conformation, induced V2-specific ADCC correlating with decreased risk of SIV acquisition. Removal of V1 from the HIV-1 clade A/E A244 envelope resulted in decreased binding to antibodies recognizing V2 in the β sheet conformation. Thus, deletion of V1 in HIV envelope immunogens may improve antibody responses to V2 virus vulnerability sites and increase the efficacy of HIV vaccine candidates.",

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author = "{Silva de Castro}, Isabela and Giacomo Gorini and Rosemarie Mason and Jason Gorman and Massimiliano Bissa and Rahman, {Mohammad A.} and Anush Arakelyan and Irene Kalisz and Stephen Whitney and Manuel Becerra-Flores and Eric Ni and Kristina Peachman and Trinh, {Hung V.} and Michael Read and Liu, {Mei Hue} and {Van Ryk}, Donald and Dominic Paquin-Proulx and Zhanna Shubin and Marina Tuyishime and Jennifer Peele and Ahmadi, {Mohammed S.} and Raffaello Verardi and Juliane Hill and Margaret Beddall and Richard Nguyen and Stamos, {James D.} and Dai Fujikawa and Susie Min and Luca Schifanella and Monica Vaccari and Veronica Galli and Doster, {Melvin N.} and Liyanage, {Namal P.M.} and Sarkis Sarkis and Francesca Caccuri and Celia LaBranche and Montefiori, {David C.} and Tomaras, {Georgia D.} and Xiaoying Shen and Margherita Rosati and Felber, {Barbara K.} and Pavlakis, {George N.} and Venzon, {David J.} and William Magnanelli and Matthew Breed and Josh Kramer and Keele, {Brandon F.} and Eller, {Michael A.} and Claudia Cicala and James Arthos and Guido Ferrari and Leonid Margolis and Marjorie Robert-Guroff and Kwong, {Peter D.} and Mario Roederer and Mangala Rao and Cardozo, {Timothy J.} and Genoveffa Franchini",

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AU - Bissa, Massimiliano

AU - Rahman, Mohammad A.

AU - Arakelyan, Anush

AU - Kalisz, Irene

AU - Whitney, Stephen

AU - Becerra-Flores, Manuel

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AU - Peele, Jennifer

AU - Ahmadi, Mohammed S.

AU - Verardi, Raffaello

AU - Hill, Juliane

AU - Beddall, Margaret

AU - Nguyen, Richard

AU - Stamos, James D.

AU - Fujikawa, Dai

AU - Min, Susie

AU - Schifanella, Luca

AU - Vaccari, Monica

AU - Galli, Veronica

AU - Doster, Melvin N.

AU - Liyanage, Namal P.M.

AU - Sarkis, Sarkis

AU - Caccuri, Francesca

AU - LaBranche, Celia

AU - Montefiori, David C.

AU - Tomaras, Georgia D.

AU - Shen, Xiaoying

AU - Rosati, Margherita

AU - Felber, Barbara K.

AU - Pavlakis, George N.

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AU - Kramer, Josh

AU - Keele, Brandon F.

AU - Eller, Michael A.

AU - Cicala, Claudia

AU - Arthos, James

AU - Ferrari, Guido

AU - Margolis, Leonid

AU - Robert-Guroff, Marjorie

AU - Kwong, Peter D.

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AU - Cardozo, Timothy J.

AU - Franchini, Genoveffa

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N2 - The efficacy of ALVAC-based HIV and SIV vaccines in humans and macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced antibodies to SIV variable region 1 (V1) inhibit anti-V2 antibody-mediated cytotoxicity and reverse their ability to block V2 peptide interaction with the α4β7 integrin. SIV vaccines engineered to delete V1 and favor an α helix, rather than a β sheet V2 conformation, induced V2-specific ADCC correlating with decreased risk of SIV acquisition. Removal of V1 from the HIV-1 clade A/E A244 envelope resulted in decreased binding to antibodies recognizing V2 in the β sheet conformation. Thus, deletion of V1 in HIV envelope immunogens may improve antibody responses to V2 virus vulnerability sites and increase the efficacy of HIV vaccine candidates.

AB - The efficacy of ALVAC-based HIV and SIV vaccines in humans and macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced antibodies to SIV variable region 1 (V1) inhibit anti-V2 antibody-mediated cytotoxicity and reverse their ability to block V2 peptide interaction with the α4β7 integrin. SIV vaccines engineered to delete V1 and favor an α helix, rather than a β sheet V2 conformation, induced V2-specific ADCC correlating with decreased risk of SIV acquisition. Removal of V1 from the HIV-1 clade A/E A244 envelope resulted in decreased binding to antibodies recognizing V2 in the β sheet conformation. Thus, deletion of V1 in HIV envelope immunogens may improve antibody responses to V2 virus vulnerability sites and increase the efficacy of HIV vaccine candidates.

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KW - molecular structure

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Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates

Abstract

Bibliographical note

Keywords

UN SDGs

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