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首页> 外文OA文献 >Comparison of Neutralizing Antibody Responses Elicited from Highly Diverse Polyvalent Heterotrimeric HIV-1 gp140 Cocktail Immunogens versus a Monovalent Counterpart in Rhesus Macaques
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Comparison of Neutralizing Antibody Responses Elicited from Highly Diverse Polyvalent Heterotrimeric HIV-1 gp140 Cocktail Immunogens versus a Monovalent Counterpart in Rhesus Macaques

机译：高度多样化的多价异源三聚体HIV-1 gp140鸡尾酒免疫原与猕猴单价对应物引起的中和抗体反应的比较

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Eliciting neutralizing antibodies capable of inactivating a broad spectrum of HIV-1 strains is a major goal of HIV-1 vaccine design. The challenge is that envelopes (Envs) of circulating viruses are almost certainly different from any Env used in a vaccine. A novel immunogen composed of a highly diverse set of gp140 Envs including subtypes A, B, C, D and F was developed to stimulate a more cross-neutralizing antibody response. Env heterotrimers composed of up to 54 different gp140s were produced with the aim of focusing the response to the conserved regions of Env while reducing the dominance of any individual hypervariable region. Heterotrimeric gp140 Envs of inter- and intra-subtype combinations were shown to bind CD4 and a panel of neutralizing monoclonal antibodies with similar affinity to monovalent UG37 gp140. Macaques immunized with six groups of heterotrimer mixtures showed slightly more potent neutralizing antibody responses in TZM-BL tier 1 and A3R5 tier 2 pseudovirus assays than macaques immunized with monovalent Env gp140, and exhibited a marginally greater focus on the CD4-binding site. Carbopol enhanced neutralization when used as an adjuvant instead of RIBI in combination with UG37 gp140. These data indicate that cross-subtype heterotrimeric gp140 Envs may elicit some improvement of the neutralizing antibody response in macaques compared to monovalent gp140 Env.
机译：消除能够使多种HIV-1毒株失活的中和抗体是HIV-1疫苗设计的主要目标。挑战在于，循环病毒的包膜（Env）几乎可以肯定与疫苗中使用的任何Env不同。开发了一种新的免疫原，它由一组高度多样化的gp140 Env组成，包括亚型A，B，C，D和F，可刺激更多的交叉中和抗体反应。产生了由多达54种不同的gp140组成的Env异源三聚体，目的是将响应集中于Env的保守区域，同时降低任何单个高变区的优势。亚型间和亚型内组合的异源三聚体gp140 Envs结合CD4和一组中和性单克隆抗体，与单价UG37 gp140具有相似的亲和力。用六组异三聚体混合物免疫的猕猴在TZM-BL 1级和A3R5 2级假病毒分析中显示出比用单价Env gp140免疫的猕猴稍强的中和抗体反应，并且对CD4结合位点的关注略微更大。当与佐剂UG37 gp140结合用作佐剂而不是RIBI时，Carbopol增强了中和作用。这些数据表明，与单价gp140 Env相比，交叉亚型异源三聚体gp140 Envs可能引起猕猴中和抗体反应的某些改善。

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