Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse functional B cell responses in primates.
Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse functional B cell responses in primates.
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DOI：
10.1084/jem.20100025
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发表时间：
2010-08-30
期刊：
影响因子：
--
通讯作者：
Karlsson Hedestam GB
中科院分区：
文献类型：
--
作者：
Sundling C;Forsell MN;O'Dell S;Feng Y;Chakrabarti B;Rao SS;Loré K;Mascola JR;Wyatt RT;Douagi I;Karlsson Hedestam GB
针对HIV-1包膜糖蛋白（Envs）的广泛中和抗体（bNAb）已被证明难以通过免疫接种引发。因此，为了鉴定有效的Env中和靶标，正在努力确定慢性感染个体中bNAb的特异性。对于预防性疫苗，同样重要的是确定在没有混杂HIV诱导的致病因素的健康灵长类动物中高度糖基化Env的免疫原性。我们使用恒河猴研究佐剂中Env三聚体刺激的B细胞应答的幅度和动力学。在三聚体接种后产生稳健的Env特异性记忆B细胞应答和高滴度的循环抗体。随后的免疫导致Env特异性IgG产生浆细胞群和循环Ab的显著扩增，其显示出增加的亲合力和中和能力。在大多数方面，用所用方案引起的中和活性上级于由基于人中单体Env免疫的方案引起的中和活性。尽管三聚体引发的反应的效力和广度，对异源直肠猿猴-HIV（SHIV）攻击的保护是适度的，说明了在粘膜部位引发足够滴度的交叉反应性保护性NAb的挑战。这些数据为设计和评价旨在刺激人类保护性HIV-1免疫应答的疫苗提供了重要信息。
Broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoproteins (Envs) have proven difficult to elicit by immunization. Therefore, to identify effective Env neutralization targets, efforts are underway to define the specificities of bNAbs in chronically infected individuals. For a prophylactic vaccine, it is equally important to define the immunogenic properties of the heavily glycosylated Env in healthy primates devoid of confounding HIV-induced pathogenic factors. We used rhesus macaques to investigate the magnitude and kinetics of B cell responses stimulated by Env trimers in adjuvant. Robust Env-specific memory B cell responses and high titers of circulating antibodies developed after trimer inoculation. Subsequent immunizations resulted in significant expansion of Env-specific IgG-producing plasma cell populations and circulating Abs that displayed increasing avidity and neutralization capacity. The neutralizing activity elicited with the regimen used was, in most aspects, superior to that elicited by a regimen based on monomeric Env immunization in humans. Despite the potency and breadth of the trimer-elicited response, protection against heterologous rectal simian-HIV (SHIV) challenge was modest, illustrating the challenge of eliciting sufficient titers of cross-reactive protective NAbs in mucosal sites. These data provide important information for the design and evaluation of vaccines aimed at stimulating protective HIV-1 immune responses in humans.
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影响因子：
4.4
作者：
Dosenovic, Pia;Chakrabarti, Bimal;Hedestam, Gunilla B. Karlsson
通讯作者：
Hedestam, Gunilla B. Karlsson
影响因子：
3.7
作者：
Corti D;Langedijk JP;Hinz A;Seaman MS;Vanzetta F;Fernandez-Rodriguez BM;Silacci C;Pinna D;Jarrossay D;Balla-Jhagjhoorsingh S;Willems B;Zekveld MJ;Dreja H;O'Sullivan E;Pade C;Orkin C;Jeffs SA;Montefiori DC;Davis D;Weissenhorn W;McKnight A;Heeney JL;Sallusto F;Sattentau QJ;Weiss RA;Lanzavecchia A
通讯作者：
Lanzavecchia A
影响因子：
56.9
作者：
ARPIN, C;DECHANET, J;LIU, YJ
通讯作者：
LIU, YJ
影响因子：
20.3
作者：
Blanchard-Rohner, Geraldine;Pulickal, Anoop S.;Pollard, Andrew J.
通讯作者：
Pollard, Andrew J.
影响因子：
3.8
作者：
Chakraborty, H;Sen, PK;Cohen, MS
通讯作者：
Cohen, MS