Voellmy Richard, Bloom David C, Vilaboa Nuria
HSF Pharmaceuticals SA, La Tour-de-Peilz, Switzerland.
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA.
Expert Rev Vaccines. 2025 Dec;24(1):146-156. doi: 10.1080/14760584.2025.2459751. Epub 2025 Feb 3.
Vaccines to prevent important infections involving, e.g. influenza viruses, severe acute respiratory syndrome-causing coronaviruses (e.g. SARS-CoV-2), respiratory syncytial viruses (RSV), and human immunodeficiency viruses (HIV) have remained insufficiently effective or are not available at all. Regulated microbes constitute novel vaccine platforms that may be employed for the development of more potent and/or more broadly effective vaccines.
We review the development and characterization of the vaccine potential of replication-competent controlled herpesviruses (RCCVs) which represent the first examples of regulated microbes used as vaccines.
The RCCVs developed to date are suitable for application to the skin and can be activated deliberately to replicate efficiently, but only transiently, in the administration site. Without activation, the RCCVs are incapable of replicating in the nervous system and elsewhere. The RCCVs were found to induce potent anti-herpetic immune responses in mice. Vaccination with RCCVs expressing an influenza virus hemagglutinin broadly protected animals against lethal influenza virus challenges. This protection appeared to be at least in part antibody-mediated. These findings support a rational expectation that RCCVs may be developed into universal, non-seasonal vaccines against influenza and, possibly, against other rapidly evolving pathogens.
预防重要感染的疫苗，例如针对流感病毒、导致严重急性呼吸综合征的冠状病毒（如SARS-CoV-2）、呼吸道合胞病毒（RSV）和人类免疫缺陷病毒（HIV）的疫苗，其效果仍然不够理想，或者根本无法获得。经过调控的微生物构成了新型疫苗平台，可用于开发更有效和/或更具广泛效力的疫苗。
我们综述了具有复制能力的可控疱疹病毒（RCCV）疫苗潜力的开发与特性，RCCV是用作疫苗的经过调控的微生物的首个实例。
迄今为止开发的RCCV适用于皮肤接种，并且可以被特意激活，以便在接种部位高效但仅短暂地复制。未经激活时，RCCV无法在神经系统和其他部位复制。研究发现，RCCV可在小鼠体内诱导强效的抗疱疹免疫反应。用表达流感病毒血凝素的RCCV进行疫苗接种，可广泛保护动物免受致命性流感病毒攻击。这种保护作用似乎至少部分是由抗体介导的。这些发现支持了一个合理的预期，即RCCV可能被开发成针对流感以及可能针对其他快速演变病原体的通用、非季节性疫苗。
