A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies.
A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies.
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DOI：
10.1038/s41598-021-84116-w
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发表时间：
2021-02-25
影响因子：
4.6
通讯作者：
Pantophlet R
中科院分区：
文献类型：
--
作者：
Bruxelle JF;Kirilenko T;Trattnig N;Yang Y;Cattin M;Kosma P;Pantophlet R
寡糖特异的广谱中和抗体(BNAbs)的出现促使人们努力开发能够诱导类似抗体的免疫原。在这里，我们报告了一种先前报道的寡核苷酸模拟物的CRM197结合物的抗原性和免疫原性。不太依赖于与HIV包膜蛋白序列相互作用的寡聚注释特异性bNAbs显示出与糖共轭的强结合，亲和力与其同源表位的报道相似。该糖结合物也被推断的寡聚糖特异性bNAbs的种系前体识别，尽管具有预期的低亲和力，支持其作为免疫原的潜力。对人类抗体转基因小鼠的免疫表明，只有刺激TLR4的佐剂配方才能产生能够结合一组重组HIV三聚体的抗体。这些抗体结合在相对适中的水平，可能解释了它们无法中和艾滋病毒传染性的原因。然而，这些发现有助于进一步了解引起HIV交叉反应的寡核苷酸特异性抗体的条件，并告知下一步改进引起的反应的步骤。
The occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM197-conjugate of a previously reported oligomannose mimetic. Oligomannose-specific bnAbs that are less dependent on interactions with the HIV envelope protein sequence showed strong binding to the glycoconjugates, with affinities approximating those reported for their cognate epitope. The glycoconjugate is also recognized by inferred germline precursors of oligomannose-specific bnAbs, albeit with the expected low avidity, supporting its potential as an immunogen. Immunization of human-antibody transgenic mice revealed that only a TLR4-stimulating adjuvant formulation resulted in antibodies able to bind a panel of recombinant HIV trimers. These antibodies bound at relatively modest levels, possibly explaining their inability to neutralize HIV infectivity. Nevertheless, these findings contribute further to understanding conditions for eliciting HIV-cross-reactive oligomannose-specific antibodies and inform on next steps for improving on the elicited response.
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影响因子：
16.6
作者：
Cao L;Pauthner M;Andrabi R;Rantalainen K;Berndsen Z;Diedrich JK;Menis S;Sok D;Bastidas R;Park SR;Delahunty CM;He L;Guenaga J;Wyatt RT;Schief WR;Ward AB;Yates JR 3rd;Burton DR;Paulson JC
通讯作者：
Paulson JC
影响因子：
3.1
作者：
Granoff, DM;McHugh, YE;VanNest, GA
通讯作者：
VanNest, GA
DOI：
10.1046/j.1432-1033.2002.03244.x
发表时间：
2002-11-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Kurokawa, T;Wuhrer, M;Geyer, R
通讯作者：
Geyer, R
影响因子：
7.8
作者：
Di Pasquale A;Preiss S;Tavares Da Silva F;Garçon N
通讯作者：
Garçon N
影响因子：
3.7
作者：
Arias, Mauricio A.;Van Roey, Griet A.;Shattock, Robin J.
通讯作者：
Shattock, Robin J.