Cremer K J, Mackett M, Wohlenberg C, Notkins A L, Moss B
Science. 1985 May 10;228(4700):737-40. doi: 10.1126/science.2986288.
In humans, herpes simplex virus causes a primary infection and then often a latent ganglionic infection that persists for life. Because these latent infections can recur periodically, vaccines are needed that can protect against both primary and latent herpes simplex infections. Infectious vaccinia virus recombinants that contain the herpes simplex virus type 1 (HSV-1) glycoprotein D gene under control of defined early or late vaccinia virus promoters were constructed. Tissue culture cells infected with these recombinant viruses synthesized a glycosylated protein that had the same mass (60,000 daltons) as the glycoprotein D produced by HSV-1. Immunization of mice with one of these recombinant viruses by intradermal, subcutaneous, or intraperitoneal routes resulted in the production of antibodies that neutralized HSV-1 and protected the mice against subsequent lethal challenge with HSV-1 or HSV-2. Immunization with the recombinant virus also protected the majority of the mice against the development of a latent HSV-1 infection of the trigeminal ganglia. This is the first demonstration that a genetically engineered vaccine can prevent the development of latency.
在人类中，单纯疱疹病毒会引发原发性感染，随后常常导致潜伏性神经节感染，并持续终生。由于这些潜伏性感染会周期性复发，因此需要能够预防原发性和潜伏性单纯疱疹感染的疫苗。构建了感染性痘苗病毒重组体，其在确定的痘苗病毒早期或晚期启动子的控制下含有1型单纯疱疹病毒（HSV-1）糖蛋白D基因。用这些重组病毒感染的组织培养细胞合成了一种糖基化蛋白，其质量（60,000道尔顿）与HSV-1产生的糖蛋白D相同。通过皮内、皮下或腹腔途径用其中一种重组病毒免疫小鼠，会产生中和HSV-1的抗体，并保护小鼠免受随后HSV-1或HSV-2的致死性攻击。用重组病毒免疫还能保护大多数小鼠免受三叉神经节潜伏性HSV-1感染的发生。这是首次证明基因工程疫苗可以预防潜伏感染的发生。
