Safety and Immunogenicity of an rVSV Lassa Fever Vaccine Candidate.

A replication-competent recombinant vesicular stomatitis virus-vectored vaccine encoding a Lassa virus (LASV) glycoprotein complex, rVSVΔG-LASV-GPC, has been developed, but data on its safety and immunogenicity are limited.

已经开发了一种复制能力完好的重组水疱性口炎病毒载体疫苗，编码拉沙病毒（LASV）糖蛋白复合体，rVSVΔG-LASV-GPC，但关于其安全性和免疫原性的数据有限。

Methods

In this phase 1, double-blindtrial conducted in the United States and Liberia, we randomly assigned healthy adults (18 to 50 years of age) to receive rVSVΔG-LASV-GPC or placebo intramuscularly.

在这项在美国和利比里亚进行的1期、双盲试验中，我们随机分配了健康的成年人（18至50岁）接受rVSVΔG-LASV-GPC或安慰剂肌肉注射。

Participants received a single vaccine dose of 2×104 plaque-forming units (PFU), 2×105 PFU, 2×106 PFU, or 2×107 PFU or placebo or received two vaccine doses of 2×107 PFU or placebo, within a window of 6 to 20 weeks.

参与者接受了单剂2×10^4、2×10^5、2×10^6或2×10^7 PFU的疫苗或安慰剂，或在6至20周的时间窗口内接受了两剂2×10^7 PFU的疫苗或安慰剂。

The side-effect profile was assessed according to the incidenceof solicited and unsolicited adverse events (primary end point).

副作用谱系根据所要求和非所要求的不良事件发生率进行评估（主要终点）。

Because Lassa fever can cause sensorineural hearing loss, hearing acuity was measured before and after the injection.

因为拉沙热可以导致感音神经性听力损失，所以在注射前后测量了听力敏锐度。

Secondary end points were levels of binding antibodies against LASV glycoprotein, neutralizing antibodies, and vaccine vector-derived viral RNA and PFU in plasma, urine, and saliva.

次要终点是针对LASV糖蛋白的结合抗体水平、中和抗体以及疫苗载体衍生的病毒RNA和PFU在血浆、尿液和唾液中的含量。

Results

A total of 114 adults were enrolled.

共有114名成年人被纳入研究。

No serious vaccine-related adverse events were reported.

未报告严重的疫苗相关不良事件。

The vaccine caused minimal local reactions and dose-dependent, mild-to-severe early-onset systemic reactogenicity events that were transient.

该疫苗引起的局部反应最小，且剂量依赖性的早期全身反应性事件从轻微到严重，但都是短暂的。

No hearing loss was detected.

未检测到听力损失。

All doses induced robust long-lasting cellular and humoral (binding and neutralizing) responses that cross-reacted against common LASV lineages.

所有剂量均诱导出强烈且持久的细胞和体液（结合和中和）反应，这些反应能够交叉反应对抗常见的LASV谱系。

No infectious vaccine virus particles were found in plasma, urine, or saliva.

在血浆、尿液或唾液中未检测到有感染性的疫苗病毒颗粒。

Conclusions

The rVSVΔG-LASV-GPC vaccine resulted in transient local and systemic reactogenicity events but no hearing loss or serious adverse events.

rVSVΔG-LASV-GPC疫苗引起了短暂的局部和全身性反应性事件，但未见听力损失或严重不良事件。

The vaccine had immunogenicity over a wide dose range in healthy adults in the United States and Liberia.

该疫苗在美利坚合众国和利比里亚的健康成人中具有广泛的剂量范围内的免疫原性。

(Funded by the Coalition for Epidemic Preparedness Innovations and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04794218; Pan African Clinical Trials Registry number, PACTR2021106625781067.).

(该研究由流行病准备创新联盟和国家过敏和传染病研究所资助；临床试验注册号为NCT04794218；泛非临床试验注册号为PACTR2021106625781067。)