Is the production of a Covid-19 vaccine using transformed Pasteurella plausible?
Is the production of a Covid-19 vaccine using transformed Pasteurella plausible?
复制标题
使用转化的巴斯德氏菌生产 Covid-19 疫苗是否可行？
DOI：
10.1136/vr.m2423
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Rycroft AN
中科院分区：
文献类型：
--
作者：
Rycroft AN
我们饶有兴趣地阅读了Aung Myint和特雷弗·琼斯的来信（VR，2020年3月28日，第186卷，第388页和VR，2020年4月4日/11日，第186卷，第419页），描述了他们在缅甸为家禽接种传染性支气管炎病毒（IBV）疫苗的经验，以及可以使用类似方法控制新冠肺炎的建议。虽然目前人们对生产新型冠状病毒疫苗的可行方法非常感兴趣，而且从兽医预防性疫苗接种中吸取经验和教训也很重要，但我们认为，这些信件中提出的基础科学的某些方面需要支持证据和进一步澄清，以证明它们是合理的。作者推测，“如果在[Covid-19]病程的早期给予含有福尔马林杀死的多杀性巴氏杆菌细胞的疫苗，通过刺激特异性保护性抗体的产生，可以有效治疗”。作者是否表明口服表达严重急性呼吸综合征冠状病毒2蛋白的灭活多能胞菌不会在人胃中消化，并会诱导病毒中和性全身抗体？作者还指出，“当与病毒感染组织的细胞裂解物混合时，多杀性P会捕获游离的病毒基因并将其整合到其基因组中”。然而，由于已知多杀性巴斯德菌难以转化（即使使用高压电穿孔），1，2和巴斯德菌科中的自然转化需要特定的摄取序列，3这似乎极不可能。这样的过程不会产生非常标准化的疫苗，但可能会有很大的批次间差异。此外，转化过程如果成功，将产生转基因产品，并且必须相当广泛地证明其适当灭活而不影响任何疫苗组分。作为一种冠状病毒，IBV具有RNA基因组，并且不包含用于转化多杀性巴斯德菌的DNA。作者如何表明病毒RNA在细菌细胞内迅速降解之前转化为DNA？4
WE read with interest the letters from Aung Myint and Trevor Jones (VR, 28 March 2020, vol 186, p 388 and VR, 4/11 April 2020, vol 186, p 419) describing their experience with vaccination of poultry against infectious bronchitis virus (IBV) in Myanmar and the proposal that a similar method could be used to control Covid-19. While a viable method for the production of a Covid-19 vaccine is of huge interest at the moment, and it is important to adopt the experience and lessons from prophylactic vaccination in veterinary medicine, we feel that some aspects of the underlying science put forward in these letters require supporting evidence and further clarification to demonstrate they are plausible. The authors speculate that ‘administration of a vaccine containing formalin-killed Pasteurella multocida cells, prepared as we described, could be effective in therapy if administered early in the course of [Covid-19], by stimulating the production of specific protective antibodies’. Are the authors suggesting that orally administered inactivated P multocidacells expressing severe acute respiratory syndrome coronavirus 2 proteins will not be digested in the human stomach and will induce virus-neutralising systemic antibodies? The authors also state that ‘when mixed with cell lysates of virusinfected tissues, P multocidatook up free viral genes and incorporated them into its genome’. However, since P multocidais known to be difficult to transform (even using high-voltage electroporation), 1, 2 and natural transformation in Pasteurellaceae requires specific uptake sequences, 3 this seems highly unlikely. Such a process would not generate a very standardised vaccine, but would likely have large batch-to-batch variations. Furthermore, the process of transformation, if successful, would result in a genetically modified product, and one would have to show quite extensively that it is appropriately inactivated without affecting any vaccine components. As a coronavirus, IBV has an RNA genome and contains no DNA with which to transform the P multocida. How do the authors suggest the viral RNA is converted to DNA before being rapidly degraded inside the bacterial cell? 4
构建用于多杀性巴氏杆菌和大肠杆菌之间的穿梭载体。
影响因子：
2.6
作者：
M. Bills;J. Medd;R. Chappel;B. Adler
通讯作者：
B. Adler
通过电穿孔转化多杀性巴氏杆菌的条件。
影响因子：
3.8
作者：
L. Jablonski;N. Sriranganathan;S. Boyle;G. Carter
通讯作者：
G. Carter