Britzke Tobias, Halwe Nico Joël, Ulrich Lorenz, Breithaupt Angele, Barut G Tuba, Wylezich Claudia, Ebert Nadine, Trüeb Bettina Salome, Thiel Volker, Hoffmann Donata, Beer Martin, Schön Jacob
Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald, Germany.
Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald, Germany.
NPJ Vaccines. 2025 May 23;10(1):104. doi: 10.1038/s41541-025-01165-2.
Live attenuated vaccines (LAV) have the potential to meet all the criteria for an efficacious vaccine. In addition to providing protection against the target disease, they offer the potential to prevent transmission, provide cross-protection by stimulating humoral and cellular immunity, and allow versatility in application routes. The SARS-CoV-2 LAV candidate, OTS-228, has demonstrated excellent safety and high efficacy in preclinical models, inducing transmission-blocking immunity and providing full protection, even against variants such as Omicron BA.2, BA.5, and XBB.1.5. However, to ensure that OTS-228 has no dose-dependent side effects and to evaluate potential risk of reversion to virulence-a known general issue with live vaccines-detailed characterization of LAV OTS-228 is essential. To address this, we conducted four different experiments using Syrian hamsters, a model for moderate to severe COVID-19. A maximum dose trial confirmed the vaccine's full attenuation and prevention of transmission, even at high doses. In addition, four intentional serial in vivo passages demonstrated the genomic stability of the vaccine and the non-infectivity of nasal washings. Furthermore, OTS-228 maintained its attenuation and immunogenicity even after 15 additional in vitro passages, providing full protection against lung infection with virulent SARS-CoV-2 strains. Finally, a low-dose experiment confirmed the high efficacy of the vaccine candidate, establishing the protective dose 50 (PD) at less than 100 TCID per hamster. Our results provide strong evidence for the safety and efficacy of the LAV candidate OTS-228 and supports its potential as a safe and effective vaccine in a highly relevant preclinical model.
减毒活疫苗(LAV)有潜力满足有效疫苗的所有标准。除了提供针对目标疾病的保护外,它们还有助于预防传播,通过刺激体液免疫和细胞免疫提供交叉保护,并在应用途径上具有灵活性。SARS-CoV-2减毒活疫苗候选株OTS-228在临床前模型中已证明具有出色的安全性和高效性,可诱导阻断传播的免疫力并提供全面保护,甚至对奥密克戎BA.2、BA.5和XBB.1.5等变体也有效。然而,为确保OTS-228没有剂量依赖性副作用,并评估其恢复毒力的潜在风险——这是减毒活疫苗的一个常见问题——对OTS-228进行详细表征至关重要。为解决这一问题,我们使用叙利亚仓鼠(一种中重度COVID-19模型)进行了四项不同的实验。最大剂量试验证实了该疫苗即使在高剂量下也能完全减毒并预防传播。此外,四次有意的体内连续传代证明了疫苗的基因组稳定性以及鼻洗液的无感染性。此外,即使在额外进行15次体外传代后,OTS-228仍保持其减毒状态和免疫原性,能为抵抗强毒株SARS-CoV-2的肺部感染提供全面保护。最后,低剂量实验证实了该候选疫苗的高效性,确定每只仓鼠的保护剂量50(PD)小于100个组织培养感染剂量(TCID)。我们的结果为候选减毒活疫苗OTS-228的安全性和有效性提供了有力证据,并支持其在高度相关的临床前模型中作为一种安全有效疫苗的潜力。
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