Department of Internal Medicine, Division of Infectious Diseases, Allergy & Immunology, Saint Louis University School of Medicine, St Louis, Missouri, USA.
The EMMES Company, Rockville, Maryland, USA.
J Infect Dis. 2023 Feb 14;227(4):522-527. doi: 10.1093/infdis/jiac067.
Previously, our group conducted the Herpevac Trial for Women, a randomized efficacy field trial of type 2 glycoprotein D (gD2) herpes simplex virus (HSV) vaccine adjuvanted with ASO4 in 8323 women. Study participants were selected to be seronegative for HSV-1 and HSV-2. We found that the vaccine was 82% protective against culture-positive HSV-1 genital disease but offered no significant protection against HSV-2 genital disease. Efficacy against HSV-1 was associated with higher levels of antibody to gD2 at enzyme-linked immunosorbent assay (ELISA).
To better understand the results of the efficacy study, we measured postvaccination concentrations of neutralizing antibody (nAb) to either HSV-1 and HSV-2 from HSV-infected study participants and matched uninfected controls. Statistical modeling was used to determine whether these responses were correlated with protection against HSV.
nAbs to either HSV-1 or HSV-2 were correlated with ELISA binding antibodies to gD2. HSV-1 or HSV-2 nAb findings support the observation of protection by higher levels of antibody against HSV-1 infection, but the lack of protection against HSV-2 remains unexplained.
The protection against HSV-1 infection observed in the Herpevac Trial for Women was associated with nAbs directed against the virus, although the power to assess this was lower in the nAb study compared with the ELISA results owing to smaller sample size.
NCT00057330.
此前，我们小组进行了 Herpevac 女性试验，这是一项针对 8323 名女性的 2 型糖蛋白 D（gD2）单纯疱疹病毒（HSV）疫苗与 AS04 佐剂的随机功效现场试验。研究参与者被选择为 HSV-1 和 HSV-2 血清阴性。我们发现该疫苗对培养阳性的 HSV-1 生殖器疾病有 82%的保护作用，但对 HSV-2 生殖器疾病没有显著保护作用。对 HSV-1 的功效与 ELISA 中针对 gD2 的抗体水平较高相关。
为了更好地理解功效研究的结果，我们测量了接种疫苗后来自 HSV 感染研究参与者和匹配的未感染对照者的针对 HSV-1 和 HSV-2 的中和抗体（nAb）的浓度。统计模型用于确定这些反应是否与对 HSV 的保护相关。
针对 HSV-1 或 HSV-2 的 nAb 与针对 gD2 的 ELISA 结合抗体相关。HSV-1 或 HSV-2 nAb 的发现支持通过针对 HSV-1 感染的更高水平抗体来提供保护的观察，但对 HSV-2 的缺乏保护仍未得到解释。
在 Herpevac 女性试验中观察到的针对 HSV-1 感染的保护与针对该病毒的 nAb 相关，尽管由于样本量较小，在 nAb 研究中评估这一点的能力低于 ELISA 结果。
NCT00057330。
