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Protection against herpes simplex virus type 2 infection in a neonatal murine model using a trivalent nucleoside-modified mRNA in lipid nanoparticle vaccine
Vaccine ( IF 4.5 ) Pub Date : 2020-10-09 , DOI: 10.1016/j.vaccine.2020.09.079
Philip C LaTourette 1 , Sita Awasthi 2 , Angela Desmond 3 , Norbert Pardi 2 , Gary H Cohen 4 , Drew Weissman 2 , Harvey M Friedman 2
Affiliation  

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.



中文翻译:

使用脂质纳米颗粒疫苗中的三价核苷修饰 mRNA 在新生小鼠模型中预防 2 型单纯疱疹病毒感染

新生儿疱疹是妊娠期生殖器疱疹感染的可怕并发症。我们最近比较了用于预防雌性小鼠和豚鼠生殖器疱疹的两种疫苗平台,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 比作为杆状病毒蛋白产生并施用的相同抗原提供更好的保护与 CpG 和明矾。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。雌性小鼠在交配前进行免疫,新生小鼠鼻内感染 HSV-2。使用 mRNA 或蛋白质疫苗时,母亲和新生儿的 IgG 结合和中和抗体水平相当。根据多个器官中的病毒滴度,这两种疫苗都可以保护第一胎和第二胎新生儿免受播散性感染。我们的结论是,这两种疫苗都能有效预防新生儿疱疹,这使得 mRNA 疫苗成为我们的首选候选疫苗,因为它能更好地预防生殖器疱疹。

更新日期:2020-10-11
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