近日，国际艾滋病疫苗行动组织 (IAVI) 的Swati B. Gupta团队研究了一种rVSV拉沙热候选疫苗的安全性和免疫原性。2025年11月6日出版的《新英格兰医学杂志》发表了这项最新研究成果。

拉沙热是一种病毒性出血性疾病，估计每年在西非造成数千人死亡。目前尚无针对拉沙热的疫苗。一种具有复制能力的重组水疱性口炎病毒载体疫苗编码了拉沙病毒（LASV）糖蛋白复合物rVSVΔG-LASV-GPC，但其安全性和免疫原性的数据有限。

在这项在美国和利比里亚进行的1期双盲试验中，研究组随机分配健康成年人（18至50岁）接受肌肉注射rVSVΔG-LASV-GPC或安慰剂。参与者在6至20周的时间窗口内接受单剂量2×10⁴斑块形成单位（PFU）、2×10⁵ PFU、2×10⁶ PFU或2×10⁷ PFU或安慰剂的疫苗接种，或接受两剂2×10⁷ PFU或安慰剂疫苗接种。根据主动和非主动不良事件的发生率（主要终点）评估副作用概况。由于拉沙热可引起感音神经性听力损失，因此在注射前后测量了听力敏锐度。次要终点是血浆、尿液和唾液中LASV糖蛋白结合抗体、中和抗体、疫苗载体衍生病毒RNA和PFU的水平。

共有114名成人被纳入研究。未报告严重的疫苗相关不良事件。该疫苗引起最小的局部反应和剂量依赖性，轻度至重度早发全身性反应原性事件是短暂的。未发现听力损失。所有剂量都诱导了持久的细胞和体液（结合和中和）反应，这些反应与常见的LASV谱系交叉反应。在血浆、尿液和唾液中未发现传染性疫苗病毒颗粒。

研究结果表明，rVSVΔG-LASV-GPC疫苗导致短暂的局部和全身反应性事件，但没有听力损失或严重不良事件。该疫苗在美国和利比里亚的健康成人中具有广泛剂量范围的免疫原性。

附：英文原文

Title: Safety and Immunogenicity of an rVSV Lassa Fever Vaccine Candidate

Author: Elissa Malkin, Marija Zaric, Mark Kieh, Lindsey R. Baden, David Fitz-Patrick, Arianna Marini, Heejin Yun, Peter Hayes, Rachel Bromell, Morolayo Ayorinde, Natalia Fernandez, Ruhani Varma, Faith Sigei, Matthew Ward, Hema Pindolia, Shayna Sewell, Fahimah Amini, Julie Blie, Barthalomew Wilson, Patrick Faley, John McCullough, Franklin Tokpah, Cecelia Wisseh, Elvis Towalid, Swapnil Hadawale, Eddy Sayeed, Devin Hunt, Nahid Keshavarzi, Burc Barin, Irina Maljkovic Berry, Christopher L. Parks, Shobhna Gopal Truter, Kathleen Walker, Johan Vekemans, Jennifer Lehrman, Michelle Engelbrecht, Mariette Malherbe, Dagna Laufer, Vincent Philiponis, Elizabeth Higgs, Gaudensia Mutua, Patricia E. Fast, Swati B. Gupta

Issue&Volume: 2025-11-06

Abstract:

BACKGROUND

No vaccine is currently available for Lassa fever, a viral hemorrhagic disease that is estimated to cause thousands of deaths each year in western Africa. 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.

METHODS

In this phase 1, double-blind trial 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. 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. The side-effect profile was assessed according to the incidence of solicited and unsolicited adverse events (primary end point). Because Lassa fever can cause sensorineural hearing loss, hearing acuity was measured before and after the injection. 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.

RESULTS

A total of 114 adults were enrolled. No serious vaccine-related adverse events were reported. The vaccine caused minimal local reactions and dose-dependent, mild-to-severe early-onset systemic reactogenicity events that were transient. No hearing loss was detected. All doses induced robust long-lasting cellular and humoral (binding and neutralizing) responses that cross-reacted against common LASV lineages. No infectious vaccine virus particles were found in plasma, urine, or saliva.

CONCLUSIONS

The rVSVΔG-LASV-GPC vaccine resulted in transient local and systemic reactogenicity events but no hearing loss or serious adverse events. The vaccine had immunogenicity over a wide dose range in healthy adults in the United States and Liberia.

DOI: NJ202511063931810

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2501073