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

被引：15

作者：

de Castro, Isabela Silva ^{[1
]}

Gorini, Giacomo ^{[1
]}

Mason, Rosemarie ^{[2
]}

Gorman, Jason ^{[3
]}

Bissa, Massimiliano ^{[1
]}

Rahman, Mohammad A. ^{[4
]}

Arakelyan, Anush ^{[5
]}

Kalisz, Irene ^{[6
]}

Whitney, Stephen ^{[6
]}

Becerra-Flores, Manuel ^{[7
]}

Ni, Eric ^{[7
]}

Peachman, Kristina ^{[8
,9
]}

Trinh, Hung, V ^{[8
,9
]}

Read, Michael ^{[9
,17
]}

Liu, Mei-Hue ^{[10
]}

Van Ryk, Donald ^{[10
]}

Paquin-Proulx, Dominic ^{[8
,9
]}

Shubin, Zhanna ^{[8
,9
]}

Tuyishime, Marina ^{[11
]}

Peele, Jennifer ^{[11
]}

Ahmadi, Mohammed S. ^{[3
]}

Verardi, Raffaello ^{[3
]}

Hill, Juliane ^{[2
]}

Beddall, Margaret ^{[2
]}

Nguyen, Richard ^{[2
]}

Stamos, James D. ^{[1
]}

Fujikawa, Dai ^{[1
]}

Min, Susie ^{[10
]}

Schifanella, Luca ^{[1
]}

Vaccari, Monica ^{[1
]}

Galli, Veronica ^{[1
]}

Doster, Melvin N. ^{[1
]}

Liyanage, Namal P. M. ^{[1
]}

Sarkis, Sarkis ^{[1
]}

Caccuri, Francesca ^{[1
]}

LaBranche, Celia ^{[11
]}

Montefiori, David C. ^{[11
]}

Tomaras, Georgia D. ^{[12
]}

Shen, Xiaoying ^{[12
]}

Rosati, Margherita ^{[13
]}

Felber, Barbara K. ^{[14
]}

Pavlakis, George N. ^{[13
]}

Venzon, David J. ^{[15
]}

Magnanelli, William ^{[16
]}

Breed, Matthew ^{[16
]}

Kramer, Josh ^{[16
]}

Keele, Brandon F. ^{[16
]}

Eller, Michael A. ^{[8
,9
]}

Cicala, Claudia ^{[10
]}

Arthos, James ^{[10
]}

机构：

[1] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA

[2] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[3] NIAID, Struct Biol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[4] NCI, Immune Biol Retroviral Infect Sect, Bethesda, MD 20892 USA

[5] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Intercellular Interact, NIH, Bethesda, MD 20892 USA

[6] Adv Biosci Labs, Rockville, MD 20850 USA

[7] NYU, Sch Med, NYU Langone Hlth, New York, NY 10016 USA

[8] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA

[9] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA

[10] NIAID, Lab Immunoregulat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[11] Duke Univ, Div Surg Sci, Sch Med, Durham, NC 27701 USA

[12] Duke Univ, Duke Human Vaccine Inst, Durham, NC 27701 USA

[13] NCI, Human Retrovirus Sect, Frederick, MD 21702 USA

[14] NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA

[15] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA

[16] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab, Frederick, MD 21704 USA

[17] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

来源：

ISCIENCE | 2021年 / 24卷 / 02期

基金：

美国国家卫生研究院;

关键词：

MONOCLONAL-ANTIBODIES; VARIABLE REGIONS; TYPE-1; ENVELOPE; NEUTRALIZATION; PROTEIN; CYTOTOXICITY; INFECTION; EFFICACY; IDENTIFICATION; ACQUISITION;

D O I：

10.1016/j.isci.2021.102047

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 alpha(4)beta(7) integrin. SIV vaccines engineered to delete V1 and favor an alpha helix, rather than a beta 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 beta 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.

引用

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