Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals.
Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals.
复制标题
DOI：
10.1038/s41467-023-42906-y
复制
发表时间：
2023-11-06
影响因子：
16.6
通讯作者：
Klein, Florian
中科院分区：
文献类型：
--
作者：
Kreer, Christoph;Lupo, Cosimo;Ercanoglu, Meryem S.;Gieselmann, Lutz;Spisak, Natanael;Grossbach, Jan;Schlotz, Maike;Schommers, Philipp;Gruell, Henning;Dold, Leona;Beyer, Andreas;Nourmohammad, Armita;Mora, Thierry;Walczak, Aleksandra M.;Klein, Florian
HIV-1广泛中和抗体（bNAb）能够抑制病毒血症并预防感染。因此，通过接种疫苗诱导它们是一个主要目标。然而，与中和其他病原体的抗体相反，HIV-1特异性bNAb经常携带可能阻止其诱导的不常见分子特征。在这里，我们进行无偏序列分析的B细胞受体库从57未感染和46慢性HIV-1或HCV感染的个人和学习概率模型来预测的可能性bNA B发展。我们正式表明，bNAb的概率较低，预示着较高的HIV-1中和活性。此外，通过其概率对bNAb进行排序允许鉴定具有上级产生概率的高效抗体作为疫苗接种方法的优先靶。重要的是，我们发现感染和未感染个体的bNAb概率相等。这意味着慢性感染并不是bNAb产生的先决条件，这使人们希望HIV-1疫苗可以诱导未感染者产生bNAb。广泛中和抗体的成功诱导是HIV疫苗开发的主要挑战。作者提供了一个框架来确定抗体序列发展的概率，并表明未感染和慢性感染的个体有相同的机会发展HIV-1中和抗体。
HIV-1 broadly neutralizing antibodies (bNAbs) are able to suppress viremia and prevent infection. Their induction by vaccination is therefore a major goal. However, in contrast to antibodies that neutralize other pathogens, HIV-1-specific bNAbs frequently carry uncommon molecular characteristics that might prevent their induction. Here, we perform unbiased sequence analyses of B cell receptor repertoires from 57 uninfected and 46 chronically HIV-1- or HCV-infected individuals and learn probabilistic models to predict the likelihood of bNAb development. We formally show that lower probabilities for bNAbs are predictive of higher HIV-1 neutralization activity. Moreover, ranking bNAbs by their probabilities allows to identify highly potent antibodies with superior generation probabilities as preferential targets for vaccination approaches. Importantly, we find equal bNAb probabilities across infected and uninfected individuals. This implies that chronic infection is not a prerequisite for the generation of bNAbs, fostering the hope that HIV-1 vaccines can induce bNAb development in uninfected people. Successful induction of broadly neutralizing antibodies is a main challenge in HIV vaccine development. The authors provide a framework to determine probabilities of antibody sequence development and show that uninfected and chronically infected individuals have the same chances to develop HIV-1 neutralizing antibodies.
登录
查看更多内容
影响因子：
64.5
作者：
Alt FW;Zhang Y;Meng FL;Guo C;Schwer B
通讯作者：
Schwer B
影响因子：
3.3
作者：
Gruell H;Klein F
通讯作者：
Klein F
影响因子：
14.9
作者：
Goujon M;McWilliam H;Li W;Valentin F;Squizzato S;Paern J;Lopez R
通讯作者：
Lopez R
影响因子：
64.5
作者：
Briney, Bryan;Sok, Devin;Jardine, Joseph G.;Kulp, Daniel W.;Skog, Patrick;Menis, Sergey;Jacak, Ronald;Kalyuzhniy, Oleksandr;de Val, Natalia;Sesterhenn, Fabian;Le, Khoa M.;Ramos, Alejandra;Jones, Meaghan;Saye-Francisco, Karen L.;Blane, Tanya R.;Spencer, Skye;Georgeson, Erik;Hu, Xiaozhen;Ozorowski, Gabriel;Adachi, Yumiko;Kubitz, Michael;Sarkar, Anita;Wilson, Ian A.;Ward, Andrew B.;Nemazee, David;Burton, Dennis R.;Schief, William R.
通讯作者：
Schief, William R.
影响因子：
7.3
作者：
Bernat, Nestor Vazquez;Corcoran, Martin;Hedestam, Gunilla B. Karlsson
通讯作者：
Hedestam, Gunilla B. Karlsson