是的灭活疫苗的常见免疫原还有nucleocapsid 问题在于.... 结合抗体不代表是中和抗体啊... 抗体又不是越多越好. Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV. J. Immunol. 181, 6337–6348 (2008). Viral vector vaccines encoding SARS-CoV S protein and nucleocapsid (N) protein provoke anti-S and anti-N IgG in immunized mice, respectively, to a similar extent. However, upon re-challenge, N protein-immunized mice show significant upregulation of pro-inflammatory cytokine secretion, increased neutrophil and eosinophil lung infiltration, and more severe lung pathology. pan-vaccine 是用新方法找coronavirus homologous neutralizing antibody epitope, 或者用新方法比方说用multiple antigenic peptide把以前做不了疫苗的保守位点, 比方说维持spike rbd三维结构的AA做成疫苗.... ( ╯□╰ )
是的灭活疫苗的常见免疫原还有nucleocapsid 问题在于.... 结合抗体不代表是中和抗体啊... 抗体又不是越多越好. Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV. J. Immunol. 181, 6337–6348 (2008). Viral vector vaccines encoding SARS-CoV S protein and nucleocapsid (N) protein provoke anti-S and anti-N IgG in immunized mice, respectively, to a similar extent. However, upon re-challenge, N protein-immunized mice show significant upregulation of pro-inflammatory cytokine secretion, increased neutrophil and eosinophil lung infiltration, and more severe lung pathology. pan-vaccine 是用新方法找coronavirus homologous neutralizing antibody epitope, 或者用新方法比方说用multiple antigenic peptide把以前做不了疫苗的保守位点, 比方说维持spike rbd三维结构的AA做成疫苗.... ( ╯□╰ ) underdoc 发表于 2021-01-20 17:56
N protein-immunized mice show significant upregulation of pro-inflammatory cytokine secretion, increased neutrophil and eosinophil lung infiltration, and more severe lung pathology. 矮油这不是实验数据？ 你知道N protein保守性有多高么。 莫非你有什么新数据？
N protein-immunized mice show significant upregulation of pro-inflammatory cytokine secretion, increased neutrophil and eosinophil lung infiltration, and more severe lung pathology. 矮油这不是实验数据？ 你知道N protein保守性有多高么。 莫非你有什么新数据？ underdoc 发表于 2021-01-20 18:40
Role of IgG against N-protein of SARS-CoV2 in COVID19 clinical outcomes COVID19-confirmed patients admitted to the hospital for hypoxemia are likely to have developed a high concentration of IgG against the N protein of SARS-CoV2. High IgG levels are associated with a higher risk of admission to the MICU and a more extended stay in the hospital. S/Co ratio > 1.5 ( signal to cut off ratio ) was associated with increased likelihood of ICU admission (p=0.047, OR=2.63 days). S/Co >1.5 was also associated with increased likelihood of staying in the hospital for more than 16 days (p=0.006, OR= 4.06) and MICU stays of more than 8 days (p=0.004, OR= 32.50) (Table 4). There was a significant correlation between IgG S/Co ratio and days in MICU as shown in Figure 2. 你有什么数据？
Role of IgG against N-protein of SARS-CoV2 in COVID19 clinical outcomes COVID19-confirmed patients admitted to the hospital for hypoxemia are likely to have developed a high concentration of IgG against the N protein of SARS-CoV2. High IgG levels are associated with a higher risk of admission to the MICU and a more extended stay in the hospital. S/Co ratio > 1.5 ( signal to cut off ratio ) was associated with increased likelihood of ICU admission (p=0.047, OR=2.63 days). S/Co >1.5 was also associated with increased likelihood of staying in the hospital for more than 16 days (p=0.006, OR= 4.06) and MICU stays of more than 8 days (p=0.004, OR= 32.50) (Table 4). There was a significant correlation between IgG S/Co ratio and days in MICU as shown in Figure 2. 你有什么数据？
underdoc 发表于 2021-01-20 18:46
这个study我也看到了，我一个colleague最近做一个的project， prelim data看来，asymptomatic group里antibody against N protein的S/Co ratio比重症组要低，而且随着时间很快下降，不过这个还要更多的数据支持。
33%有效是Early protection, 随着时间推移应该会逐渐增强的。 'Early protection' Clalit, Israel's largest healthcare provider, covering most of the population, compared the medical records of 200,000 vaccinated over-60s with the same number belonging to unvaccinated people. For two weeks after the first dose, both groups tested positive for the virus at roughly the same rate. But then those vaccinated started to show 33% fewer new infections than the others. "This is very early protection," said Clalit chief innovation officer, Ran Balicher, who is also a public health professor advising the government. And "already there is a 33% fall". Infections continued to decline after that. But there were too few for Prof Balicher to calculate by what percentage.
https://www.biorxiv.org/content/10.1101/2021.01.15.426911v1.full.pdf
但是南非的这个突变毒株确实是往不好的方向走了一大步，再来一个这样的突变的话疫苗带来的体液免疫（中和抗体）还有多少有效性就难说了。一个比较正面的消息是疫苗除了体液免疫还有细胞免疫，T细胞识别相近抗原的能力比中和抗体要强。最近几个星期关于这些突变毒株的研究进一步说明疫苗带来的细胞免疫至关重要，灭活疫苗的T细胞免疫可以忽略（暂且不谈Th2 bias的问题），应付这些突变毒株的能力堪忧。
补一张图，红色是辉瑞白色是Moderna，纵轴是中和滴度。最右边那个图是包含了南非毒株上3个最重要突变的假病毒。
1.1倍到3倍
那这个下降很significant啊，是不是？。。。。
还好，其实下降3倍可能都比一般的康复血清强。科兴疫苗的中和滴度只有康复患者血清的1/3，细胞免疫基本可以忽略，都有50%的有效率呢
是的，就算只靠T细胞也能避免大部分重症
T细胞两种牌子的疫苗都会有吗？ 马上要出来的强生会产生T细胞吗？
这时候，rna疫苗的优势就出来了，只需要调整就是了
每1-2年加强针，注射调整后的
目前来看, 两种mRNA疫苗都有, AZ的腺病毒效果更好 强生的也有而且比较强, novavax的重组蛋白好像也有. 不用太担心, 放低期望, 这个疫苗不会形成群体免疫, 打过疫苗的人还可能得病, 还可能传染他人. 不过不会重症打完疫苗以后当成个流感就行了.
其实灭活脊灰疫苗差不多也是这样, 不也一样管用..
不见得, 抗原差异过小可能会有OAS
mark
灭活疫苗有pan coronavirus vaccine的潜质。
这些variants 变异主要集中在spike protein上。灭活疫苗的免疫原不仅限于刺突蛋白。所以，大概率对各种变种都有一定保护作用。
Funding for Program Projects To Advance Pan-Coronavirus Vaccine Candidates Funding News Edition: November 18, 2020
泛冠状病毒疫苗能够解决新冠变异毒株和未来新型冠状病毒的威胁。
只针对特定毒株刺突蛋白的疫苗显然不能是pan-croronavirus vaccine candidate.
是的灭活疫苗的常见免疫原还有nucleocapsid 问题在于.... 结合抗体不代表是中和抗体啊... 抗体又不是越多越好. Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV. J. Immunol. 181, 6337–6348 (2008). Viral vector vaccines encoding SARS-CoV S protein and nucleocapsid (N) protein provoke anti-S and anti-N IgG in immunized mice, respectively, to a similar extent. However, upon re-challenge, N protein-immunized mice show significant upregulation of pro-inflammatory cytokine secretion, increased neutrophil and eosinophil lung infiltration, and more severe lung pathology.
pan-vaccine 是用新方法找coronavirus homologous neutralizing antibody epitope, 或者用新方法比方说用multiple antigenic peptide把以前做不了疫苗的保守位点, 比方说维持spike rbd三维结构的AA做成疫苗....
( ╯□╰ )
我不是专业的但专家都说灭活疫苗产生一大堆结合抗体 没用 有用的只有中和抗体
你问的专家是水货呗。
加强学习。
搞学问最忌讳cherrypicking, 先选观点再挑数据。
按这个说法以前的那四个普通冠状病毒免疫以后是不是应该就可以对付现在的新冠了？
这句话没错，不过好像应该送给你自己。。。
我在加强学习， ref The potential danger of suboptimal antibody responses in COVID-19 Akiko Iwasaki & Yexin Yang
Nature Reviews Immunology
作者是 岩崎明子 (Akiko Iwasaki) 免疫专家，美国科学院院士HHMI
你是谁啊有什么专著拿出来让大家学习一下？
是的，有说法人们对新冠反应差别很大和这个有关系。未必能提供完全保护，但是某种程度保护是可能的。
生物是实验科学，数据最大。没有这个，谁说都不算。
那为啥你说的就对的呢？？？
我说的话都有qualification，没注意到么？
N protein-immunized mice show significant upregulation of pro-inflammatory cytokine secretion, increased neutrophil and eosinophil lung infiltration, and more severe lung pathology. 矮油这不是实验数据？ 你知道N protein保守性有多高么。
莫非你有什么新数据？
老鼠，而且是非常artificial的setting。
没有什么用处。
Role of IgG against N-protein of SARS-CoV2 in COVID19 clinical outcomes
COVID19-confirmed patients admitted to the hospital for hypoxemia are likely to have developed a high concentration of IgG against the N protein of SARS-CoV2. High IgG levels are associated with a higher risk of admission to the MICU and a more extended stay in the hospital.
S/Co ratio > 1.5 ( signal to cut off ratio ) was associated with increased likelihood of ICU admission (p=0.047, OR=2.63 days). S/Co >1.5 was also associated with increased likelihood of staying in the hospital for more than 16 days (p=0.006, OR= 4.06) and MICU stays of more than 8 days (p=0.004, OR= 32.50) (Table 4). There was a significant correlation between IgG S/Co ratio and days in MICU as shown in Figure 2.
你有什么数据？
那个人是带任务的，去年五月份就拿着个喉咙里有病毒肺部还有炎症的动物实验结果狂吹灭活疫苗“是免疫原性最好的疫苗”，“完全保护”了六只恒河猴，直接屏蔽掉就是了。
https://forums.huaren.us/showtopic.html?topicid=2553570&fid=398&page=5
这个study我也看到了，我一个colleague最近做一个的project， prelim data看来，asymptomatic group里antibody against N protein的S/Co ratio比重症组要低，而且随着时间很快下降，不过这个还要更多的数据支持。
楼主楼主，那请问灭活疫苗对南非的变种有用吗？谢谢哦！
这个没做实验谁知道啊。。。我个人不是很乐观
你打脸太狠了 不过我喜欢
我觉得用asymptomatic不太合适，因为asymptomatic的机制都不清楚 我觉得用首诊时covid scale 2-3 ，做cohort s/o和outcome比较合适
当然这个可能太理想化了，。。
斗文献的技能在工作时候也很有用 平时要多练习。。
Novavax啊。还有JNJ一针方案的三期结果应该这几天就要公布了，不过我觉得他们两针疫苗的方案免疫数据要好的多
为啥opt out？是去打已经批准了的疫苗吗？
LOL.
确信你看得懂paper?
33%有效是Early protection, 随着时间推移应该会逐渐增强的。 'Early protection' Clalit, Israel's largest healthcare provider, covering most of the population, compared the medical records of 200,000 vaccinated over-60s with the same number belonging to unvaccinated people. For two weeks after the first dose, both groups tested positive for the virus at roughly the same rate. But then those vaccinated started to show 33% fewer new infections than the others. "This is very early protection," said Clalit chief innovation officer, Ran Balicher, who is also a public health professor advising the government. And "already there is a 33% fall". Infections continued to decline after that. But there were too few for Prof Balicher to calculate by what percentage.
以色列这四分之一是居民还是国民。。。他们那边大比例的非国民。。。。