Safety and Immunogenicity of LC16m8, an Attenuated Smallpox Vaccine in Vaccinia-Naive Adults
Safety and Immunogenicity of LC16m8, an Attenuated Smallpox Vaccine in Vaccinia-Naive Adults
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DOI：
10.1093/infdis/jir527
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发表时间：
2011-11-01
影响因子：
6.4
通讯作者：
Greenberg, Richard N.
中科院分区：
文献类型：
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作者：
Kennedy, Jeffrey S.;Gurwith, Marc;Greenberg, Richard N.
方法。我们进行了一项 I/II 期临床试验，比较了 LC16m8 与 Dryvax 在未接种过牛痘的受试者中的安全性和免疫原性。评估了不良事件、心电图和心脏毒性实验室测试以及疫苗接种部位的病毒培养。评估了牛痘、猴痘和天花的中和滴度，并通过干扰素 (IFN)-γ 酶联免疫吸附斑点和淋巴细胞增殖测定来测量细胞介导的免疫反应。结果。接种 LC16m8 后的局部和全身反应与 Dryvax 后报道的相似。两种疫苗均未发现与心脏毒性一致的临床显着异常。两种疫苗均实现了抗痘苗、抗天花和抗猴痘中和抗体滴度 > 1:40，尽管在接种后第 30 天 LC16m8 的平均空斑减少中和滴度显着低于 Dryvax，用于抗 NYCBH 痘苗 (P < .01)、抗猴痘 (P < .001) 和抗天花 (P < .001）。 LC16m8 产生强大的细胞免疫反应，其淋巴细胞增殖趋势高于 Dryvax (P = .06)，但 IFN-gamma ELISPOT 较低 (P = .02)。结论。 LC16m8 产生针对多种痘病毒（包括牛痘、猴痘和天花）的中和抗体滴度，以及广泛的 T 细胞反应，表明 LC16m8 可能有效保护个体免受天花感染。临床试验注册。 NCT00103584。
Methods. We conducted a phase I/II clinical trial that compared the safety and immunogenicity of LC16m8 with Dryvax in vaccinia-naive participants. Adverse events were assessed, as were electrocardiography and laboratory testing for cardiotoxicity and viral culturing of the vaccination sites. Neutralization titers to vaccinia, monkeypox, and variola major were assessed and cell-mediated immune responses were measured by interferon (IFN)-gamma enzyme-linked immunosorbent spot and lymphoproliferation assays.Results. Local and systemic reactions after vaccination with LC16m8 were similar to those reported after Dryvax. No clinically significant abnormalities consistent with cardiac toxicity were seen for either vaccine. Both vaccines achieved antivaccinia, antivariola, and antimonkeypox neutralizing antibody titers > 1:40, although the mean plaque reduction neutralization titer of LC16m8 at day 30 after vaccination was significantly lower than Dryvax for anti-NYCBH vaccinia (P < .01), antimonkeypox (P < .001), and antivariola (P < .001). LC16m8 produced robust cellular immune responses that trended higher than Dryvax for lymphoproliferation (P = .06), but lower for IFN-gamma ELISPOT (P = .02).Conclusions. LC16m8 generates neutralizing antibody titers to multiple poxviruses, including vaccinia, monkeypox, and variola major, and broad T-cell responses, indicating that LC16m8 may have efficacy in protecting individuals from smallpox.Clinical Trials Registration. NCT00103584.