Abstract:
Vaccine development for herpes simplex virus 2 (HSV-2) has been attempted, but no vaccines are yet available. A plasmid-based reverse genetics system for Rotavirus (RV), which can cause gastroenteritis, allows the generation of recombinant RV containing foreign genes. In this study, we sought to develop simian RV (SA11) as a vector to express HSV-2 glycoprotein D (gD2) and evaluated its immunogenicity in mice. We generated the recombinant SA11-gD2 virus (rSA11-gD2) and confirmed its ability to express gD2 in vitro. The virus was orally inoculated into suckling BALB/c mice and into 8-week-old mice. Serum IgG and IgA titers against RV and gD2 were measured by ELISA. In the 8-week-old mice inoculated with rSA11-gD2, significant increases in not only antibodies against RV but also IgG against gD2 were demonstrated. In the suckling mice, antibodies against RV were induced, but gD2 antibody was not detected. Diarrhea observed after the first inoculation of rSA11-gD2 in suckling mice was similar to that induced by the parent virus. A gD2 expressing simian RV recombinant, which was orally inoculated, induced IgG against gD2. This strategy holds possibility for genital herpes vaccine development.
摘要:
已经尝试了针对单纯疱疹病毒2(HSV-2)的疫苗开发,但目前还没有疫苗。基于质粒的轮状病毒(RV)反向遗传学系统,会导致胃肠炎,允许产生含有外源基因的重组RV。在这项研究中,我们试图开发猿猴RV(SA11)作为表达HSV-2糖蛋白D(gD2)的载体,并评估其在小鼠中的免疫原性。我们产生了重组SA11-gD2病毒(rSA11-gD2),并证实了其在体外表达gD2的能力。将该病毒口服接种到哺乳BALB/c小鼠和8周龄小鼠中。通过ELISA测量针对RV和gD2的血清IgG和IgA滴度。在接种rSA11-gD2的8周龄小鼠中,证明了不仅针对RV的抗体而且针对gD2的IgG的显著增加。在乳鼠中,诱导抗RV抗体,但未检测到gD2抗体。在乳鼠中首次接种rSA11-gD2后观察到的腹泻与亲本病毒诱导的腹泻相似。一个gD2表达猿猴RV重组,口服接种,诱导针对gD2的IgG。该策略为生殖器疱疹疫苗的开发提供了可能性。