iou2007
学术研究数据分析
正文
主要有以下几点
灭活疫苗有强烈的TH1倾向，所以不能诱发细胞免疫。只能诱导体液免疫。体液免疫主要依赖血清中和抗体，目前研究基本认为抗体存在的时间不长，所以灭活疫苗引发的免疫力有效期很短。而MRNA疫苗能同时诱发体液和细胞免疫，所以保护力要长的多。
灭活疫苗的抗原为外源性质。在灭活过程中，病毒的RNA失活，病毒进入人体后不再复制。而疫苗本身的抗原是外源性的。相比之下，MRNA和腺病毒载体疫苗产生的抗原蛋白是内源性的。要知道，免疫过程是非常复杂的，不同人之间细微的差别会造成免疫原性的巨大差别。在人体内部产生的内源性抗原，诱导产生的抗体会更加有效果。
灭活疫苗诱导的抗体很多，大部分不具备中和病毒的效果，反而会有潜在可能成为病毒的带路人。新冠病馆毒的中和抗体主要是针对病毒的S蛋白。非中和性的抗体很多时候不但起不到消灭病毒的作用，反而会成为病毒进入细胞的捷径。ADE效应就由此而来。
灭活病毒的中和抗体滴度远远低于康复患者血清抗体浓度。根据<柳叶刀>文章，科兴疫苗中和抗体滴度只有康复患者血清中和抗体滴度的14-40%。而MRNA疫苗中和抗体滴度是康复患者血清中和抗体滴度的几倍。
灭活疫苗在智利等国家的失败几乎是必然的。
所以灭活疫苗本身中和抗体滴度低是致命的以外，细胞免疫的弱势是更大的隐患。
Memory responses are responsible for protection from reinfection and are essential for effective vaccination. The observation that memory B cell responses do not decay after 6.2 months34,35,42, but instead continue to evolve, is strongly suggestive that individuals who are infected with SARS-CoV-2 could mount a rapid and effective response to the virus upon re-exposure.
在另一篇自然文章里根据87名康复者跟踪研究，血清Igm和IgG抗体显著下降，血清中和活性6个月后下降五倍。而记忆b细胞数量保持不变。而且记忆b细胞出现对RBD效率增加，显示人体免疫持续进化
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.
新冠和流感是完全不一样的。新冠是单正链RNA病毒，而流感是多条负链RNA。
NATURE文章里写到，COVID变种在突破RBD5，6，22，23，26，38这些表位的时候，表位6、13、14、32、39、40、41、42、43高度保守
而建议未来疫苗设计为了避免选择和逃避，抗体疗法应该由针对不重叠或高度保守的表位
Human neutralizing monoclonal antibodies to the SARS-CoV-2 RBD can be categorized as belonging to four classes on the basis of their target regions on the RBD7. Class-1 and -2 antibodies are among the most potent and also the most abundant antibodies5,6,22,23,26,38. These antibodies target epitopes that overlap or are closely associated with RBD residues K417, E484 and N501. They are frequently sensitive to mutation in these residues and select for K417N, E484K and N501Y mutations in SARS-CoV-2 S expression libraries in yeast and VSV13,16,32. To avert selection and escape, antibody therapies should be composed of combinations of antibodies that target non-overlapping or highly conserved epitopes6,13,14,32,39,40,41,42,43.
下面MODERNA发在自然的文章，MRNA疫苗和自然免疫产生的中和抗体针对RBD相同表位。用辉瑞和MODERNA疫苗产生的抗体几乎相同，而其他表位的抗体是否由疫苗激发，有待研究
MRNA疫苗的抗体特异性，非常强。
The mRNA-based SARS-CoV-2 vaccines are safe and effective, and are being deployed globally to prevent infection and disease. The vaccines elicit antibody responses against the RBD (the major target of neutralizing antibodies22,23,24,25,26,27) in a manner that resembles natural infection. Notably, the neutralizing antibodies produced by mRNA vaccination target the same epitopes as those produced by natural infection. Data are consistent with SARS-CoV-2 S trimers translated from the injected RNA adopting a range of different conformations. Moreover, different individuals immunized with the Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccines produce closely related, and nearly identical, antibodies. Whether or not neutralizing antibodies to epitopes other than those involving the RBD are elicited by vaccination remains to be determined.
基于mRNA的SARS-CoV-2疫苗是安全有效的，并正在全球部署，以预防感染和疾病。这些疫苗以一种类似于自然感染的方式激发针对RBD(中和抗体22、23、24、25、26、27的主要目标)的抗体反应。值得注意的是，mRNA疫苗产生的中和抗体与自然感染产生的中和抗体针对相同的表位。数据与SARS-CoV-2S三聚体从注射的RNA翻译而来，采用了一系列不同的构象是一致的。此外，用MODERNA(mRNA-1273)或辉瑞生物科技(BNT162b2)疫苗免疫的不同个体产生密切相关且几乎相同的抗体。除了RBD以外的其他表位的中和抗体是否通过疫苗接种而产生，还有待确定。
回复 'iou2007' 的评论 :
流感虽然是变异最多，如今，我们都以认为去年远远低估了新冠的变异速度。 病毒变异的速度取决于多重因素：病毒在人群中繁殖的代数，及被感染人群的迁徙，免疫压力与病毒的fitness。新冠的变异速度有可能会超过流感。
去看看流感和新冠病毒的结构，就能理解为什么流感变异那么快。
原因是多方面的，有疫苗的不同，疫苗剂量的不同，人群的不同，及流形毒株的不同。
市场上流感疫苗的种类有灭活疫苗（鸡胚生长的，细胞生长的含佐剂），减毒疫苗，重组蛋白疫苗。
你这个说法本身就有问题。佐剂就是疫苗的一部分。
由佐剂引发的TH1/TH2不平衡，也就是疫苗的不平衡。
我哪里说了，TH1/TH2不平衡是抗原造成？不要随便断章取义。
流感比新冠变异能力强。
你的这些不妥，恐怕是真的不妥。
mRNA疫苗所用的LNP是一种新型佐剂，可以诱导 Th1 response。
回复 'iou2007' 的评论 :
灭活疫苗有强烈得TH2倾向，th1/th2不平衡，细胞免疫不行。这个本身没有错。
MRNA疫苗也能诱导大量的非中和抗体，
灭活疫苗诱导的抗体很多，大部分不具备中和病毒的效果，反而会有潜在可能成为病毒的带路人
目前研究基本认为抗体存在的时间不长，所以灭活疫苗引发的免疫力有效期很短。而MRNA疫苗能同时诱发体液和细胞免疫，所以保护力要长的多。
灭活疫苗引发的中和抗体滴度比较低，不如MRNA疫苗引发的中和抗体滴度高。
而灭活疫苗本身的抗原是外源性的。相比之下，MRNA和腺病毒载体疫苗产生的抗原蛋白是内源性的
研究文章一般认为平衡的th1/th2的免疫效果更加理想。
因为博客被推荐，无法修改了。那只是个输入错误，但是不能改了。
灭活疫苗有强烈得TH2倾向，th1/th2不平衡，细胞免疫不行。这个本身没有错。
已经指出来了。
有不少人在写些科普，本是好事，但缺少专业知识，以讹传讹。
First Commercial Hepatitis B Vaccine
In 1981, the FDA approved a more sophisticated plasma-derived hepatitis B vaccine for human use. This “inactivated” type of vaccine involved the collection of blood from hepatitis B virus-infected (HBsAg-positive) donors. The pooled blood was subjected to multiple steps to inactive the viral particles that included formaldehyde and heat treatment (or “pasteurization”). Merck Pharmaceuticals manufactured this plasma vaccine as "Heptavax," which was the first commercial hepatitis B virus vaccine. The use of this vaccine was discontinued in 1990 and it is no longer available in the U.S.
Current Recombinant Hepatitis B Vaccines
In 1986, research resulted in a second generation of genetically engineered (or DNA recombinant) hepatitis B vaccines. These new approved vaccines are synthetically prepared and do not contain blood products - it is impossible to get hepatitis B from the new recombinant vaccines that are currently approved in the United States.
刨去细菌类疫苗。目前在应用的病毒灭活疫苗不多。
只有甲型肝炎，流感，狂犬病等几种。流感疫苗效率不高，和现在新冠灭活疫苗差不多。
其他病毒疫苗，有减毒活疫苗，比如乙脑，重组蛋白疫苗，比如乙肝
你的疫苗卡上只有部分是灭活疫苗。很多已经进化为非灭活疫苗了。比如乙肝。
除了这次covid mRNA 疫苗外，以前的好几十种疫苗都是不是灭活疫苗？我两个孩子疫苗卡好长，难道不是都是灭活疫苗吗？所以它们全是失败的？
我是一直被医生蒙了，还是被您蒙了？