Department of Rheumatology and Immunology, University Hospital, Bern, Switzerland.
Department of BioMedical Research, University of Bern, Bern, Switzerland.
Allergy. 2022 Jan;77(1):243-257. doi: 10.1111/all.15080. Epub 2021 Sep 20.
SARS-CoV-2 caused one of the most devastating pandemics in the recent history of mankind. Due to various countermeasures, including lock-downs, wearing masks, and increased hygiene, the virus has been controlled in some parts of the world. More recently, the availability of vaccines, based on RNA or adenoviruses, has greatly added to our ability to keep the virus at bay; again, however, in some parts of the world only. While available vaccines are effective, it would be desirable to also have more classical vaccines at hand for the future. Key feature of vaccines for long-term control of SARS-CoV-2 would be inexpensive production at large scale, ability to make multiple booster injections, and long-term stability at 4℃.
Here, we describe such a vaccine candidate, consisting of the SARS-CoV-2 receptor-binding motif (RBM) grafted genetically onto the surface of the immunologically optimized cucumber mosaic virus, called CuMV -RBM.
Using bacterial fermentation and continuous flow centrifugation for purification, the yield of the production process is estimated to be >2.5 million doses per 1000-litre fermenter run. We demonstrate that the candidate vaccine is highly immunogenic in mice and rabbits and induces more high avidity antibodies compared to convalescent human sera. The induced antibodies are more cross-reactive to mutant RBDs of variants of concern (VoC). Furthermore, antibody responses are neutralizing and long-lived. In addition, the vaccine candidate was stable for at least 14 months at 4℃.
Thus, the here presented VLP-based vaccine may be a good candidate for use as conventional vaccine in the long term.
SARS-CoV-2 引发了近代人类历史上最具破坏性的大流行之一。由于包括封锁、戴口罩和增加卫生措施在内的各种对策，该病毒在世界某些地区已得到控制。最近，基于 RNA 或腺病毒的疫苗的可用性大大提高了我们控制病毒的能力；然而，在世界上的某些地区仍然如此。虽然现有疫苗有效，但未来还希望有更多的经典疫苗可供使用。长期控制 SARS-CoV-2 的疫苗的关键特征将是大规模低成本生产、多次加强注射的能力和在 4℃下的长期稳定性。
在这里，我们描述了一种这样的疫苗候选物，它由 SARS-CoV-2 受体结合基序（RBM）基因移植到免疫优化的黄瓜花叶病毒（称为 CuMV-RBM）表面制成。
使用细菌发酵和连续流离心进行纯化，估计每 1000 升发酵罐的生产过程产量>250 万剂。我们证明，候选疫苗在小鼠和兔子中具有高度免疫原性，并诱导出比恢复期人类血清更高亲和力的抗体。诱导的抗体对关注变体（VOC）的突变 RBD 具有更高的交叉反应性。此外，抗体反应具有中和作用和长期持久性。此外，候选疫苗在 4℃下至少稳定 14 个月。
因此，这里提出的基于 VLP 的疫苗可能是长期常规疫苗使用的良好候选物。
