Protection against herpes simplex virus type 2 infection in a neonatal murine model using a trivalent nucleoside-modified mRNA in lipid nanoparticle vaccine.
Protection against herpes simplex virus type 2 infection in a neonatal murine model using a trivalent nucleoside-modified mRNA in lipid nanoparticle vaccine.
复制标题
DOI：
10.1016/j.vaccine.2020.09.079
复制
发表时间：
2020-11-03
期刊：
影响因子：
5.5
通讯作者：
Friedman HM
中科院分区：
文献类型：
--
作者：
LaTourette PC 2nd;Awasthi S;Desmond A;Pardi N;Cohen GH;Weissman D;Friedman HM
三价mRNA和蛋白质疫苗在母鼠和幼鼠中产生强大的中和抗体。三价mRNA和蛋白质疫苗预防多器官感染。疫苗保护的持久性延伸到第二代窝仔。生殖器疱疹是一种常见的生殖器疱疹病毒感染。我们最近比较了两种用于预防雌性小鼠和豚鼠生殖器疱疹的疫苗平台，并确定使用脂质纳米颗粒中核苷修饰的mRNA表达的HSV-2糖蛋白C，D和E比杆状病毒蛋白产生的相同抗原提供更好的保护，并与CpG和明矾一起施用。在这里，我们评估了mRNA和蛋白质免疫对新生儿疱疹的保护作用。在交配前对雌性小鼠进行免疫，并用HSV-2鼻内感染新生小鼠。使用mRNA或蛋白质疫苗，母亲和新生儿中的IgG结合和中和抗体水平相当。根据多个器官中的病毒滴度，两种疫苗均可保护第一窝和第二窝新生儿免受播散性感染。我们的结论是，这两种疫苗在预防新生儿疱疹方面都是有效的，这使得mRNA疫苗成为我们基于更好地预防生殖器疱疹的首选候选疫苗。
Trivalent mRNA and protein vaccines produce robust neutralizing antibodies in dams and pups. Trivalent mRNA and protein vaccines prevent infection of multiple organs. Durability of vaccine protection extends into second-generation litters. Neonatal herpes is a dreaded complication of genital herpes infection in pregnancy. We recently compared two vaccine platforms for preventing genital herpes in female mice and guinea pigs and determined that HSV-2 glycoproteins C, D and E expressed using nucleoside-modified mRNA in lipid nanoparticles provided better protection than the same antigens produced as baculovirus proteins and administered with CpG and alum. Here we evaluated mRNA and protein immunization for protection against neonatal herpes. Female mice were immunized prior to mating and newborns were infected intranasally with HSV-2. IgG binding and neutralizing antibody levels in mothers and newborns were comparable using the mRNA or protein vaccines. Both vaccines protected first and second litter newborns against disseminated infection based on virus titers in multiple organs. We conclude that both vaccines are efficacious at preventing neonatal herpes, which leaves the mRNA vaccine as our preferred candidate based on better protection against genital herpes.
登录
查看更多内容
DOI：
10.1038/nrd.2017.243
发表时间：
2018-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Pardi N;Hogan MJ;Porter FW;Weissman D
通讯作者：
Weissman D
影响因子：
11.8
作者：
Wald, A;Ashley-Morrow, R
通讯作者：
Ashley-Morrow, R
影响因子：
5.4
作者：
Awasthi, Sita;Huang, Jialing;Friedman, Harvey M.
通讯作者：
Friedman, Harvey M.
影响因子：
6.4
作者：
Kao, Carol M.;Goymer, Jessica;Herold, Betsy C.
通讯作者：
Herold, Betsy C.
影响因子：
158.5
作者：
Zaman, K.;Roy, Eliza;Steinhoff, Mark C.
通讯作者：
Steinhoff, Mark C.