The goals of a genital herpes vaccine are to prevent painful genital lesions and reduce or eliminate subclinical infection that risks transmission to partners and newborns. We evaluated a trivalent glycoprotein vaccine containing herpes simplex virus type 2 (HSV-2) entry molecule glycoprotein D (gD2) and two immune evasion molecules: glycoprotein C (gC2), which binds complement C3b, and glycoprotein E (gE2), which blocks immunoglobulin G (IgG) Fc activities. The trivalent vaccine was administered as baculovirus proteins with CpG and alum, or the identical amino acids were expressed using nucleoside-modified mRNA in lipid nanoparticles (LNPs). Both formulations completely prevented genital lesions in mice and guinea pigs. Differences emerged when evaluating subclinical infection. The trivalent protein vaccine prevented dorsal root ganglia infection, and day 2 and 4 vaginal cultures were negative in 23 of 30 (73%) mice compared with 63 of 64 (98%) in the mRNA group (P = 0.0012). In guinea pigs, 5 of 10 (50%) animals in the trivalent subunit protein group had vaginal shedding of HSV-2 DNA on 19 of 210 (9%) days compared with 2 of 10 (20%) animals in the mRNA group that shed HSV-2 DNA on 5 of 210 (2%) days (P = 0.0052). The trivalent mRNA vaccine was superior to trivalent proteins in stimulating ELISA IgG antibodies, neutralizing antibodies, antibodies that bind to crucial gD2 epitopes involved in entry and cell-to-cell spread, CD4⁺ T cell responses, and T follicular helper and germinal center B cell responses. The trivalent nucleoside-modified mRNA-LNP vaccine is a promising candidate for human trials.

生殖器疱疹疫苗的目标是预防生殖器疼痛，并减少或消除可能传播给伴侣和新生儿的亚临床感染。我们评估了一种三价糖蛋白疫苗，该疫苗包含2型单纯疱疹病毒（HSV-2）进入分子糖蛋白D（gD2）和两个免疫逃逸分子：结合补体C3b的糖蛋白C（gC2）和可阻断补体的糖蛋白E（gE2）免疫球蛋白G（IgG）Fc活性。将三价疫苗以杆状病毒蛋白的形式与CpG和明矾一起施用，或者使用核苷修饰的mRNA在脂质纳米颗粒（LNP）中表达相同的氨基酸。两种制剂均能完全预防小鼠和豚鼠的生殖器损伤。在评估亚临床感染时出现差异。三价蛋白疫苗可预防背根神经节感染，P = 0.0012）。在豚鼠中，三价亚基蛋白组中的10只（50％）动物中有5只在210天（9％）天中有19天出现了HSV-2 DNA的阴道脱落，而mRNA组中的10只（20％）动物中有2只阴道在210（2％）天中的5天中释放出HSV-2 DNA（P = 0.0052）。三价mRNA疫苗在刺激ELISA IgG抗体，中和抗体，与进入和细胞间扩散，CD4 ⁺ T细胞反应，T滤泡辅助和生发中心B涉及的重要gD2表位结合的抗体方面优于三价蛋白细胞反应。三价核苷修饰的mRNA-LNP疫苗是用于人类试验的有前途的候选药物。