Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial.

We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine.

我们评估了LASSARAB，这是一种使用灭活狂犬病病毒作为载体的拉沙病毒（Josiah株）糖蛋白复合疫苗。

We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart.

我们开展了一项随机对照、剂量递增的1期试验。共有54名参与者接受了两次肌肉注射LASSARAB，分别含有700（15人）、1,400（15人）或2,800（14人）相对单位的抗原，这些抗原与TLR-4激动剂3D-6-酰基PHAD-SE佐剂配制，或者使用了许可的狂犬病疫苗对照（10人），两次注射间隔28天。

This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61.

本研究方案规定的中期分析报告了截至第61天的主要安全性评估和次要免疫原性评估结果。

There were no prespecified hypotheses or formal power calculations.

没有预先设定的假设或正式的效能计算。

All primary safety end points demonstrated an acceptable safety profile.

所有主要的安全终点均显示出可接受的安全性特征。

After dose 1, local solicited adverse events occurred in 86.7-100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3-71.4% and 60.0% of controls.

第一剂后，LASSARAB组的局部不良反应发生率为86.7-100.0%，对照组为80%；全身不良反应发生率为33.3-71.4%，对照组为60.0%。

After dose 2, local solicited adverse events occurred in 66.7-86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3-71.4% of LASSARAB groups and 55.6% of controls.

第二剂后，LASSARAB组的局部不良反应发生率为66.7-86.7%，对照组为55.6%；全身不良反应发生率为53.3-71.4%，对照组为55.6%。

Events were predominantly mild and self-limited.

事件主要是轻度且自限性的。

Unsolicited adverse events occurred in 28.6-60.0% of LASSARAB groups and 20.0% of controls.

在LASSARAB组中，非请求数不良事件的发生率为28.6-60.0%，而对照组为20.0%。

No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred.

未发生严重不良事件、免疫介导的疾病或感音神经性耳聋。

Safety laboratory abnormalities occurred in 13.3-66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe).

LASSARAB组的安全实验室异常发生在13.3-66.7%之间，对照组为30.0%（14例轻度，6例中度，无重度）。

After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls.

经过两剂接种，Lassa病毒GPC IgG ELISA血清转化（≥四倍增长）在所有接受LASSARAB的受试者（44人中的100.0%）中实现，而在对照组（10人中的0.0%）中未实现。

Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml-1) were also 100% across all groups, including controls.

所有组别（包括对照组）的狂犬病糖蛋白IgG ELISA血清转化（≥四倍增长）和通过快速荧光焦点抑制试验（RFFIT）的中和抗体血清保护（≥0.5 IU ml-1）均为100%。

LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses.

LASSARAB + 3D-6-酰基磷酸化六酰基二糖（PHAD）-SE对拉沙病毒和狂犬病病毒显示出良好的安全性和免疫原性。

The per-protocol final study report will include safety and durability through day 394.

按方案的最终研究报告将包括至第394天的安全性和持久性数据。

ClinicalTrials.gov identifier NCT06546709 .

临床试验注册号 NCT06546709 .