iou2007
學術研究數據分析
正文
主要有以下幾點
滅活疫苗有強烈的TH1傾向，所以不能誘發細胞免疫。隻能誘導體液免疫。體液免疫主要依賴血清中和抗體，目前研究基本認為抗體存在的時間不長，所以滅活疫苗引發的免疫力有效期很短。而MRNA疫苗能同時誘發體液和細胞免疫，所以保護力要長的多。
滅活疫苗的抗原為外源性質。在滅活過程中，病毒的RNA失活，病毒進入人體後不再複製。而疫苗本身的抗原是外源性的。相比之下，MRNA和腺病毒載體疫苗產生的抗原蛋白是內源性的。要知道，免疫過程是非常複雜的，不同人之間細微的差別會造成免疫原性的巨大差別。在人體內部產生的內源性抗原，誘導產生的抗體會更加有效果。
滅活疫苗誘導的抗體很多，大部分不具備中和病毒的效果，反而會有潛在可能成為病毒的帶路人。新冠病館毒的中和抗體主要是針對病毒的S蛋白。非中和性的抗體很多時候不但起不到消滅病毒的作用，反而會成為病毒進入細胞的捷徑。ADE效應就由此而來。
滅活病毒的中和抗體滴度遠遠低於康複患者血清抗體濃度。根據<柳葉刀>文章，科興疫苗中和抗體滴度隻有康複患者血清中和抗體滴度的14-40%。而MRNA疫苗中和抗體滴度是康複患者血清中和抗體滴度的幾倍。
滅活疫苗在智利等國家的失敗幾乎是必然的。
所以滅活疫苗本身中和抗體滴度低是致命的以外，細胞免疫的弱勢是更大的隱患。
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.
在另一篇自然文章裏根據87名康複者跟蹤研究，血清Igm和IgG抗體顯著下降，血清中和活性6個月後下降五倍。而記憶b細胞數量保持不變。而且記憶b細胞出現對RBD效率增加，顯示人體免疫持續進化
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樣的。新冠是單正鏈RNA病毒，而流感是多條負鏈RNA。
NATURE文章裏寫到，COVID變種在突破RBD5，6，22，23，26，38這些表位的時候，表位6、13、14、32、39、40、41、42、43高度保守
而建議未來疫苗設計為了避免選擇和逃避，抗體療法應該由針對不重疊或高度保守的表位
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.
下麵MODERNA發在自然的文章，MRNA疫苗和自然免疫產生的中和抗體針對RBD相同表位。用輝瑞和MODERNA疫苗產生的抗體幾乎相同，而其他表位的抗體是否由疫苗激發，有待研究
MRNA疫苗的抗體特異性，非常強。
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.
基於mRNA的SARS-CoV-2疫苗是安全有效的，並正在全球部署，以預防感染和疾病。這些疫苗以一種類似於自然感染的方式激發針對RBD(中和抗體22、23、24、25、26、27的主要目標)的抗體反應。值得注意的是，mRNA疫苗產生的中和抗體與自然感染產生的中和抗體針對相同的表位。數據與SARS-CoV-2S三聚體從注射的RNA翻譯而來，采用了一係列不同的構象是一致的。此外，用MODERNA(mRNA-1273)或輝瑞生物科技(BNT162b2)疫苗免疫的不同個體產生密切相關且幾乎相同的抗體。除了RBD以外的其他表位的中和抗體是否通過疫苗接種而產生，還有待確定。
回複 'iou2007' 的評論 :
流感雖然是變異最多，如今，我們都以認為去年遠遠低估了新冠的變異速度。 病毒變異的速度取決於多重因素：病毒在人群中繁殖的代數，及被感染人群的遷徙，免疫壓力與病毒的fitness。新冠的變異速度有可能會超過流感。
去看看流感和新冠病毒的結構，就能理解為什麽流感變異那麽快。
原因是多方麵的，有疫苗的不同，疫苗劑量的不同，人群的不同，及流形毒株的不同。
市場上流感疫苗的種類有滅活疫苗（雞胚生長的，細胞生長的含佐劑），減毒疫苗，重組蛋白疫苗。
你這個說法本身就有問題。佐劑就是疫苗的一部分。
由佐劑引發的TH1/TH2不平衡，也就是疫苗的不平衡。
我哪裏說了，TH1/TH2不平衡是抗原造成？不要隨便斷章取義。
流感比新冠變異能力強。
你的這些不妥，恐怕是真的不妥。
mRNA疫苗所用的LNP是一種新型佐劑，可以誘導 Th1 response。
回複 'iou2007' 的評論 :
滅活疫苗有強烈得TH2傾向，th1/th2不平衡，細胞免疫不行。這個本身沒有錯。
MRNA疫苗也能誘導大量的非中和抗體，
滅活疫苗誘導的抗體很多，大部分不具備中和病毒的效果，反而會有潛在可能成為病毒的帶路人
目前研究基本認為抗體存在的時間不長，所以滅活疫苗引發的免疫力有效期很短。而MRNA疫苗能同時誘發體液和細胞免疫，所以保護力要長的多。
滅活疫苗引發的中和抗體滴度比較低，不如MRNA疫苗引發的中和抗體滴度高。
而滅活疫苗本身的抗原是外源性的。相比之下，MRNA和腺病毒載體疫苗產生的抗原蛋白是內源性的
研究文章一般認為平衡的th1/th2的免疫效果更加理想。
因為博客被推薦，無法修改了。那隻是個輸入錯誤，但是不能改了。
滅活疫苗有強烈得TH2傾向，th1/th2不平衡，細胞免疫不行。這個本身沒有錯。
已經指出來了。
有不少人在寫些科普，本是好事，但缺少專業知識，以訛傳訛。
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.
刨去細菌類疫苗。目前在應用的病毒滅活疫苗不多。
隻有甲型肝炎，流感，狂犬病等幾種。流感疫苗效率不高，和現在新冠滅活疫苗差不多。
其他病毒疫苗，有減毒活疫苗，比如乙腦，重組蛋白疫苗，比如乙肝
你的疫苗卡上隻有部分是滅活疫苗。很多已經進化為非滅活疫苗了。比如乙肝。
除了這次covid mRNA 疫苗外，以前的好幾十種疫苗都是不是滅活疫苗？我兩個孩子疫苗卡好長，難道不是都是滅活疫苗嗎？所以它們全是失敗的？
我是一直被醫生蒙了，還是被您蒙了？