Vaccine induced antibodies to the first variable loop of human immunodeficiency virus type 1 gp120, mediate antibody-dependent virus inhibition in macaques

被引：19

作者：

Bialuk, Izabela ^{[1
,2
]}

Whitney, Stephen ^{[5
]}

Andresen, Vibeke ^{[1
]}

Florese, Ruth H. ^{[3
]}

Nacsa, Janos ^{[1
]}

Cecchinato, Valentina ^{[1
]}

Valeri, Valerio W. ^{[1
]}

Heraud, Jean-Michel ^{[1
]}

Gordon, Shari ^{[1
]}

Parks, Robyn Washington ^{[1
]}

Montefiori, David C. ^{[6
]}

Venzon, David ^{[4
]}

Demberg, Thorsten ^{[3
]}

Robert-Guroff, Marjorie ^{[3
]}

Landucci, Gary ^{[7
]}

Forthal, Donald N. ^{[7
]}

Franchini, Genoveffa ^{[1
]}

机构：

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

[2] Med Univ Bialystok, Dept Gen & Expt Pathol, PL-15222 Bialystok, Poland

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

[4] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA

[5] Adv BioSci Labs, Kensington, MD 20895 USA

[6] Duke Univ, Med Ctr, Dept Surg, Lab AIDS Vaccine Res & Dev, Durham, NC 27710 USA

[7] Univ Calif Irvine, Div Infect Dis, Dept Med, Sch Med, Irvine, CA 92697 USA

来源：

VACCINE | 2011年 / 30卷 / 01期

关键词：

ADCC; ADCVI; V1; Vaccine; N-LINKED GLYCOSYLATION; EXTRACELLULAR ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODIES; RHESUS MACAQUES; NEUTRALIZING ANTIBODIES; CELLULAR CYTOTOXICITY; SIVMAC251; CHALLENGE; INFECTED MACAQUES; REPLICATION-COMPETENT; LYMPHOCYTE DEPLETION;

D O I：

10.1016/j.vaccine.2011.10.040

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The role of antibodies directed against the hyper variable envelope region V1 of human immunodeficiency virus type 1 (HIV-1), has not been thoroughly studied. We show that a vaccine able to elicit strain-specific non-neutralizing antibodies to this region of gp120 is associated with control of highly pathogenic chimeric SHIV89.6p replication in rhesus macaques. The vaccinated animal that had the highest titers of antibodies to the amino terminus portion of VI, prior to challenge, had secondary antibody responses that mediated cell killing by antibody-dependent cellular cytotoxicity (ADCC), as early as 2 weeks after infection and inhibited viral replication by antibody-dependent cell-mediated virus inhibition (ADCVI), by 4 weeks after infection. There was a significant inverse correlation between virus level and binding antibody titers to the envelope protein, (R = -0.83,p = 0.015), and ADCVI (R= -0.84 p = 0.044). Genotyping of plasma virus demonstrated in vivo selection of three SHIV89.6p variants with changes in potential N-linked glycosylation sites in Vi. We found a significant inverse correlation between virus levels and titers of antibodies that mediated ADCVI against all the identified V1 virus variants. A significant inverse correlation was also found between neutralizing antibody titers to SHIV89.6 and virus levels (R = -0.72 p = 0.0050). However, passive inoculation of purified immunoglobulin from animal M316, the macaque that best controlled virus, to a naive macaque, resulted in a low serum neutralizing antibodies and low ADCVI activity that failed to protect from SHIV89.6p challenge. Collectively, while our data suggest that anti-envelope antibodies with neutralizing and non-neutralizing Fc(R-dependent activities may be important in the control of SHIV replication, they also demonstrate that low levels of these antibodies alone are not sufficient to protect from infection. Published by Elsevier Ltd.

引用

页码：78 / 94

页数：17

共 73 条

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