mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.
mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.
复制标题
mRNA编码的HIV-1 ENV三聚体铁蛋白纳米颗粒会诱导单克隆抗体中和小鼠中和异源HIV-1分离株。
DOI：
10.1016/j.celrep.2022.110514
复制
发表时间：
2022-03-15
期刊：
影响因子：
8.8
通讯作者：
Haynes BF
中科院分区：
文献类型：
--
作者：
Mu Z;Wiehe K;Saunders KO;Henderson R;Cain DW;Parks R;Martik D;Mansouri K;Edwards RJ;Newman A;Lu X;Xia SM;Eaton A;Bonsignori M;Montefiori D;Han Q;Venkatayogi S;Evangelous T;Wang Y;Rountree W;Korber B;Wagh K;Tam Y;Barbosa C;Alam SM;Williams WB;Tian M;Alt FW;Pardi N;Weissman D;Haynes BF
脂质纳米粒中核苷修饰的mRNA（mRNA-LNP）作为COVID-19疫苗的成功预示着疫苗开发的新时代。对于HIV-1，多价包膜（Env）三聚体蛋白纳米颗粒与单独的三聚体相比是用于引发广泛中和抗体（bnAb）B细胞谱系的上级免疫原。复合多价纳米颗粒免疫原与mRNA的成功表达尚未得到证实。在这里，我们表明mRNA可以编码铁蛋白纳米颗粒上的抗原性Env三聚体，其启动bnAb前体B细胞扩增，并在bnAb前体VH + VL敲入小鼠中诱导血清自体2级中和活性。下一代测序证实了关键突变的获得，并分离出了中和异源HIV-1分离株的单克隆抗体。因此，mRNA-LNP可以编码复杂的免疫原，并可用于设计用于HIV-1疫苗开发的生殖系靶向和顺序加强免疫原。mRNA疫苗对COVID-19非常有效。Mu等人证明使用mRNA表达在铁蛋白纳米颗粒上支架化的HIV-1 Env三聚体。小鼠中的mRNA疫苗接种诱导自体2级中和抗体和关键功能突变。分离的单克隆抗体中和异源HIV-1分离株。
The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. For HIV-1, multivalent envelope (Env) trimer protein nanoparticles are superior immunogens compared with trimers alone for priming of broadly neutralizing antibody (bnAb) B cell lineages. The successful expression of complex multivalent nanoparticle immunogens with mRNAs has not been demonstrated. Here, we show that mRNAs can encode antigenic Env trimers on ferritin nanoparticles that initiate bnAb precursor B cell expansion and induce serum autologous tier 2 neutralizing activity in bnAb precursor VH + VL knock-in mice. Next-generation sequencing demonstrates acquisition of critical mutations, and monoclonal antibodies that neutralize heterologous HIV-1 isolates are isolated. Thus, mRNA-LNP can encode complex immunogens and may be of use in design of germline-targeting and sequential boosting immunogens for HIV-1 vaccine development. mRNA vaccines are highly effective against COVID-19. Mu et al. demonstrate the use of mRNA to express HIV-1 Env trimers scaffolded on ferritin nanoparticles. mRNA vaccination in mice induced autologous tier 2 neutralizing antibodies and key functional mutations. Isolated monoclonal antibodies neutralized heterologous HIV-1 isolates.
登录
查看更多内容
影响因子：
32.4
作者：
Alameh MG;Tombácz I;Bettini E;Lederer K;Sittplangkoon C;Wilmore JR;Gaudette BT;Soliman OY;Pine M;Hicks P;Manzoni TB;Knox JJ;Johnson JL;Laczkó D;Muramatsu H;Davis B;Meng W;Rosenfeld AM;Strohmeier S;Lin PJC;Mui BL;Tam YK;Karikó K;Jacquet A;Krammer F;Bates P;Cancro MP;Weissman D;Luning Prak ET;Allman D;Locci M;Pardi N
通讯作者：
Pardi N
DOI：
10.1097/qad.0000000000000106
发表时间：
2014-01-14
期刊：
AIDS (London, England)
影响因子：
--
作者：
Hraber P;Seaman MS;Bailer RT;Mascola JR;Montefiori DC;Korber BT
通讯作者：
Korber BT
影响因子：
56.9
作者：
Haynes, BF;Fleming, J;Alam, SM
通讯作者：
Alam, SM
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
1.5
作者：
ALLAWAY, GP;DAVISBRUNO, KL;MADDON, PJ
通讯作者：
MADDON, PJ