Protection from Herpes Simplex Virus (HSV)-2 Infection with Replication-Defective HSV-2 or Glycoprotein D2 Vaccines in HSV-1-Seropositive and HSV-1-Seronegative Guinea Pigs
Protection from Herpes Simplex Virus (HSV)-2 Infection with Replication-Defective HSV-2 or Glycoprotein D2 Vaccines in HSV-1-Seropositive and HSV-1-Seronegative Guinea Pigs
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DOI：
10.1086/605645
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发表时间：
2009-10-01
影响因子：
6.4
通讯作者：
Cohen, Jeffrey I.
中科院分区：
文献类型：
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作者：
Hoshino, Yo;Pesnicak, Lesley;Cohen, Jeffrey I.
背景资料。单纯疱疹病毒(HSV)-2候选疫苗由明胶中的糖蛋白D(GD2)和单磷酰脂A(MPL)组成，可减少HSV-1血清阴性女性的生殖器疱疹疾病，但对男性或HSV-1血清阳性女性无影响。为了确定HSV-1血清状态对不同疫苗效果的影响，我们在明矾/MPL中测试了GD2，在弗氏佐剂中测试了GD2，在HSV-1血清阳性或HSV-1血清阴性豚鼠中测试了复制缺陷HSV-2突变体d15-29。与GD2疫苗相比，在HSV-1血清阴性动物中，d15-29诱导的中和抗体滴度最高，经阴道攻击野生型病毒后，阴道脱落率降低，神经节中HSV DNA水平降低，生殖器疱疹急性期和复发率降低。在HSV-1血清阳性动物中，3种疫苗诱导的中和抗体效价相似，对急性和复发性生殖器疱疹表现出相似的保护作用，但d15-29疫苗比GD2疫苗更能减少攻击后的阴道脱落。D15-29疫苗对HSV-1阳性和HSV-1阴性豚鼠都是有效的疫苗，在减少两组动物攻击后的病毒脱落方面优于GD2疫苗。DL5-29可能减少HSV-2的传播。
Background. A herpes simplex virus (HSV)-2 candidate vaccine consisting of glycoprotein D (gD2) in alum and monophosphoryl lipid A (MPL) reduced genital herpes disease in HSV-1-seronegative women but not in men or HSV-1-seropositive women.Methods. To determine the effect of HSV-1 serostatus on effectiveness of different vaccines, we tested gD2 in alum/MPL, gD2 in Freund's adjuvant, and dl5-29 (a replication-defective HSV-2 mutant) in HSV-1-seropositive or HSV-1-seronegative guinea pigs.Results. In HSV-1-seronegative animals, dl5-29 induced the highest titers of neutralizing antibody, and after vaginal challenge with wild-type virus, dl5-29 resulted in lower rates of vaginal shedding, lower levels of HSV DNA in ganglia, and a trend for less acute and recurrent genital herpes, compared with the gD2 vaccines. In HSV-1-seropositive animals, all 3 vaccines induced similar titers of neutralizing antibodies and showed similar levels of protection against acute and recurrent genital herpes after vaginal challenge with wild-type virus, but dl5-29 reduced vaginal shedding after challenge more than did the gD2 vaccines.Conclusions. dl5-29 Is an effective vaccine in both HSV-1-seropositive and HSV-1- seronegative guinea pigs and was superior to gD2 vaccines in reducing virus shedding after challenge in both groups of animals. dl5-29 Might reduce transmission of HSV-2.