接种疫苗诱导产生的抗单纯疱疹病毒糖蛋白D肽抗体不能保护单纯疱疹病毒2型血清阴性女性免受单纯疱疹病毒2型感染。
Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2 infection in HSV-2 seronegative women.
作者信息
Gilbert Peter B, Excler Jean-Louis, Tomaras Georgia D, Carpp Lindsay N, Haynes Barton F, Liao Hua-Xin, Montefiori David C, Rerks-Ngarm Supachai, Pitisuttithum Punnee, Nitayaphan Sorachai, Kaewkungwal Jaranit, Kijak Gustavo H, Tovanabutra Sodsai, Francis Donald P, Lee Carter, Sinangil Faruk, Berman Phillip W, Premsri Nakorn, Kunasol Prayura, O'Connell Robert J, Michael Nelson L, Robb Merlin L, Morrow Rhoda, Corey Lawrence, Kim Jerome H
机构信息
Statistical Center for HIV/AIDS Research and Prevention, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
出版信息
PLoS One. 2017 May 11;12(5):e0176428. doi: 10.1371/journal.pone.0176428. eCollection 2017.
BACKGROUND
In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX® B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX® B/E vaccine contains two gp120 envelope glycoproteins, one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244 isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV-1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV-2 gD sequence. We assessed whether vaccine-induced anti-gD antibodies protected females against HSV-2 acquisition in RV144.
METHODS
Of the women enrolled in RV144, 777 vaccine and 807 placebo recipients were eligible and randomly selected according to their pre-vaccination HSV-1 and HSV-2 serostatus for analysis. Immunoglobulin G (IgG) and IgA responses to gD were determined by a binding antibody multiplex assay and HSV-2 serostatus was determined by Western blot analysis. Ninety-three percent and 75% of the vaccine recipients had anti-gD IgG and IgA responses two weeks post last vaccination, respectively. There was no evidence of reduction in HSV-2 infection by vaccination compared to placebo recipients over 78 weeks of follow-up. The annual incidence of HSV-2 infection in individuals who were HSV-2 negative at baseline or HSV-1 positive and HSV-2 indeterminate at baseline were 4.38/100 person-years (py) and 3.28/100 py in the vaccine and placebo groups, respectively. Baseline HSV-1 status did not affect subsequent HSV-2 acquisition. Specifically, the estimated odds ratio of HSV-2 infection by Week 78 for female placebo recipients who were baseline HSV-1 positive (n = 422) vs. negative (n = 1120) was 1.14 [95% confidence interval 0.66 to 1.94, p = 0.64)]. No evidence of reduction in the incidence of HSV-2 infection by vaccination was detected.
CONCLUSIONS
AIDSVAX® B/E containing gD did not confer protection from HSV-2 acquisition in HSV-2 seronegative women, despite eliciting anti-gD serum antibodies.
背景
在HIV-1疫苗试验RV144中，采用ALVAC-HIV初免并结合AIDSVAX® B/E加强免疫，在首次接种疫苗后42个月时可使HIV-1感染率降低31%。二价AIDSVAX® B/E疫苗包含两种gp120包膜糖蛋白，一种来自B亚型HIV-1 MN毒株，另一种来自CRF01_AE A244亚型毒株。每种包膜糖蛋白都含有一个高度保守的27个氨基酸的单纯疱疹病毒1型糖蛋白D（gD）标签序列，该序列与单纯疱疹病毒2型gD序列具有93%的序列同一性。我们评估了疫苗诱导的抗gD抗体是否能保护RV144中的女性免受HSV-2感染。
方法
在参与RV144的女性中，根据其接种疫苗前的HSV-1和HSV-2血清学状态，随机选择777名疫苗接种者和807名安慰剂接受者进行分析。通过结合抗体多重检测法测定对gD的免疫球蛋白G（IgG）和IgA反应，并通过蛋白质印迹分析确定HSV-2血清学状态。分别有93%和75%的疫苗接种者在最后一次接种疫苗两周后出现抗gD IgG和IgA反应。在78周的随访期内，与安慰剂接受者相比，未发现接种疫苗可降低HSV-2感染的证据。在基线时HSV-2阴性或基线时HSV-1阳性且HSV-2不确定的个体中，疫苗组和安慰剂组HSV-2感染的年发病率分别为4.38/100人年（py）和3.28/100 py。基线HSV-1状态不影响随后的HSV-2感染。具体而言，对于基线HSV-1阳性（n = 422）与阴性（n = 1120）的女性安慰剂接受者，到第78周时HSV-2感染的估计比值比为1.14 [95%置信区间0.66至1.94，p = 0.64]。未检测到接种疫苗可降低HSV-2感染发病率的证据。
结论
尽管可诱导产生抗gD血清抗体，但含有gD的AIDSVAX® B/E并不能保护HSV-2血清阴性的女性免受HSV-2感染。
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