Live Attenuated Zoster Vaccine Boosts Varicella Zoster Virus (VZV)-Specific Humoral Responses Systemically and at the Cervicovaginal Mucosa of Kenyan VZV-Seropositive Women.
Live Attenuated Zoster Vaccine Boosts Varicella Zoster Virus (VZV)-Specific Humoral Responses Systemically and at the Cervicovaginal Mucosa of Kenyan VZV-Seropositive Women.
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DOI：
10.1093/infdis/jiy320
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发表时间：
2018-09-08
期刊：
影响因子：
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通讯作者：
Institute of Tropical and Infectious Diseases (UNITID) Group and the Kenyan AIDS Vaccine Initiative–Institute of Clinical Research (KAVI-ICR) Team
中科院分区：
文献类型：
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作者：
Perciani CT;Sekhon M;Hundal S;Farah B;Ostrowski MA;Anzala AO;McKinnon LR;Jaoko W;MacDonald KS;Institute of Tropical and Infectious Diseases (UNITID) Group and the Kenyan AIDS Vaccine Initiative–Institute of Clinical Research (KAVI-ICR) Team
我们发现vzv血清阳性的妇女在胃肠道和生殖器粘膜维持vzv特异性体液免疫，这种免疫可以在接种疫苗后增强。我们的发现鼓励进一步研究VZV作为包括HIV在内的疫苗的潜在载体。减毒水痘带状疱疹病毒（VZV）是一种很有前途的重组疫苗载体。由于人类免疫缺陷病毒（HIV）疫苗被认为需要粘膜免疫原性，我们在VZVOka疫苗接种后对粘膜vzv特异性体液免疫进行了表征。肯尼亚成年vzv血清阳性妇女（n = 44）接受了单剂带状疱疹VZVOka活疫苗。使用内部糖蛋白酶联免疫吸附试验，在血浆和粘膜分泌物中纵向跟踪对病毒的遗忘反应，并监测安全性和反应原性。在我们的队列中（n = 288），还描述了VZV血清阳性率和对病毒的基线反应。接种疫苗不仅能全身增强抗vzv抗体应答，还能增强宫颈阴道黏膜的抗vzv免疫，免疫球蛋白G （P < 0.0001）和免疫球蛋白a (IgA) （P = 0.004）较接种前和接种后4周分别升高2.9倍和1.6倍（P = 0.004）。基线分析显示，vzv血清阳性妇女的胃肠道和生殖器粘膜有高亲和力抗体。唾液中VZV特异性IgA的检测是检测VZV感染的灵敏工具。VZVOka疫苗在vzv血清阳性的肯尼亚成年妇女中是安全且具有免疫原性的。我们提供了令人信服的证据，证明VZV能够诱导生殖器粘膜免疫。NCT02514018。
We show that VZV-seropositive women sustain VZV-specific humoral immunity at the gastrointestinal and genital mucosa and that this immunity can be boosted upon vaccination. Our findings encourage further investigation of VZV as a potential vector in vaccines including HIV. Attenuated varicella zoster virus (VZV) is a promising vector for recombinant vaccines. Because human immunodeficiencyvirus (HIV) vaccines are believed to require mucosal immunogenicity, we characterized mucosal VZV-specific humoral immunity following VZVOka vaccination. Adult Kenyan VZV-seropositive women (n = 44) received a single dose of the live zoster VZVOka vaccine. The anamnestic responses to the virus were followed longitudinally in both plasma and mucosal secretions using an in-house glycoprotein enzyme-linked immunosorbent assay and safety and reactogenicity monitored. VZV seroprevalence and baseline responses to the virus were also characterized in our cohorts (n = 288). Besides boosting anti-VZV antibody responses systemically, vaccination also boosted anti-VZV immunity in the cervicovaginal mucosa with a 2.9-fold rise in immunoglobulin G (P < .0001) and 1.6-fold rise in immunoglobulin A (IgA) (P = .004) from the time before immunization and 4 weeks postvaccination. Baseline analysis demonstrated high avidity antibodies at the gastrointestinal and genital mucosa of VZV-seropositive women. Measurement of VZV-specific IgA in saliva is a sensitive tool for detecting prior VZV infection. VZVOka vaccine was safe and immunogenic in VZV-seropositive adult Kenyan women. We provided compelling evidence of VZV ability to induce genital mucosa immunity. NCT02514018.
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