SARS-CoV-2的疫苗研發製造的策略:
1.去活化病毒疫苗(inactivated virus vaccines):
病毒已經是被用物理的或化學的去活化(Viruses are physically or chemically inactivated),但是仍然保存病毒顆粒的完整性(preserve the integrity of the virus paticle),它們充當免疫抗原(immunogen)。
2.病毒類似的顆粒或奈米顆粒的疫苗(Virus -like particle or nanoparticle vaccines):
結構性的病毒的蛋白質已經被共同表現(structural viral proteins are co-expressed),,形成沒有感染性的顆粒(form non-infectious particles),來當作疫苗的免疫抗原(vaccine immunogen),它們類似真實的類病毒(real virions)但是缺乏病毒的基因體(lack the virus genome)。
3.蛋白質次單元的疫苗(Protein subunit vaccines):
這種策略只有包括關鍵性的病毒的蛋白質或胜太(only key proteins or peptides),它們能夠在細菌(bacteria)酵母菌(yeast)昆蟲或脯乳類細胞(insect or mammalian cells)中在人體外被製造(manufactured in vitro),目前最大多數的在臨床期和臨床前期階段登錄在案候選的SARS-CoV-2疫苗,都是根據這種策略研發製造的。
4.病毒引導導航導向的疫苗(virus-vectored vaccines):
編碼致病原抗原的基因(genes encoding pathogen antigen),是被導入非複製的或複製的病毒載體(cloned into non-replicating or replicating virus vectors)例如腺病毒(adenvirus),這些抗原在免疫化作用後,由被轉換的宿主細胞產生(the antigens are produced by transduced host cells after immunization)。
5.DNA和mRNA疫苗(DNA and mRNA vaccines):
DNA和mRNA疫苗(DNA and mRNA vaccines),有可以快速製造用來抵抗突現性的致病原的優勢(DNA and mRNA vaccines have the advantage of rapid manufacturing against pathogens),DNA 疫苗(DNA vaccines),藉由再重組的DNA 質體所編碼的病毒的抗原(viral antigens encoded by a recombinant DNA plasmid),在宿主細胞中經由次序性的轉錄到轉譯的過程產生(produced in host cells via sequential transcription-to translation process)。相反地,mRNA 疫苗(mRNA vaccines)是藉由在人體外的轉錄過程被合成(synthesized by in vitro transcription),它們經由在人體內的直接的蛋白質轉譯,在細胞質中產生病毒的抗原(they produce viral antigens in the cytoplasm through direct protein trsnslation in vivo)。
6.活的減毒的病毒疫苗(Live-attenuated virus vaccines):
在這種策略中,病毒是藉由在人體外或人體內的過程或反向的遺傳的突變的產生作用而被減毒(virus is attenuated by in vitro or in vivo passage or reverse genetic mutagenesis),這個結果病毒變成沒有致病性或變成弱的致病性(the resulting virus becomes non-pathogenic or weakly pathogenic),但是仍然維持保持類似活的病毒感染的免疫抗原性(retains immunogenecity by mimicking live virus infection)。
資料來源:
Viral targets for vaccines against COVID-19
Nature Reviews Immunology(2020)18 DEC 2020)
感謝 #Cheng_Sheng_Tai 醫師提供資料
同時也有1部Youtube影片,追蹤數超過16萬的網紅夠維根Go Vegan,也在其Youtube影片中提到,這是個常見的迷思,不只一般的民眾會搞混 連專業的醫療人員都不太清楚... FB粉絲專頁:https://www.facebook.com/GoVeganTW 提倡一種新的生活態度,透過動畫宣導"動物權利"! 特別感謝"台灣素食營養學會"贊助 臺灣素食營養學會官網:http://www.twvns...
in vivo and in vitro 在 Mr. Muscular - 你的網上健身百科全書 Facebook 的最讚貼文
年紀和肌肉發展的關係
年紀大等於較小訓練效果⁉️
🤔🤔🤔
頂級運動員退休的原因是他們太老嗎?
頂級運動員年齡平均值為20多歲[10]。而奧林匹克舉重選手的年齡平均值為26歲 。[9]但我們細心想想,頂級運動員退休的原因通常都是傷患、有關藥物使用的風險(drug-related health risks)、較佳的工作機會等等...
當我們更加深入探討有關力量和肌肥大的時候,我們會發現健力運動員都會在35歲(平均值)時達到最佳的狀態[11]。而有關健美運動員的研究不多,但當我們細心觀察那些傑出的健美選手時,會發現他們達到職業巔峰的時期通常都是在30-40多歲。
例子:Ronnie Coleman, Phil Heath, Dorian Yates, Arnold Schwarzenegger, Jay Cutler...
💪🏻💪🏻💪🏻
標題: Association of age with muscle size and strength before and after short-term resistance training in young adults [2]
圖2
研究背景
研究對象為18至39歲的男性和女性,使用磁力共振掃描(MRI)檢測肱二頭肌橫截面面積和測試肘屈肌群的一下最大力量(1RM),然後進行為期12星期的單邊手臂(非主用手)重量訓練。
訓練期結束後,再次使用磁力共振掃描(MRI)檢測肱二頭肌橫截面面積和測試肘屈肌群的一下最大力量。對比訓練前和訓練後的結果,最後得出當中的改變。
圖2A, 對象的肱二頭肌經歷12星期的重量訓練後,都有所增長。而各年齡層的肌肉增長沒有實際分別。在成年初期,年齡不會影響肌肉對重量訓練的反應。
圖2B,
年紀和二頭彎舉一下最大力量(1RM)有着負相聯的關係。
標題: Epidemiology of Sarcopenia [1]
研究背景及設計:
在明尼蘇達州的人群研究 (population-based study in Rochester, Minnesota)
年齡層抽樣方式提取數據 (Age stratified sample of men and women from the community)
😨😨😨
大眾而言,肌少症在大約20歲開始。不論性別,隨着人們年紀的增長,肌肉量都會穩定地下降。
既然肌少症在20歲開始...但是為什麼健力和健美運動員會在30~40多歲時達到運動表現的巔峰?
流失肌肉量·真正的成因⁉️
研究要點✅
1️⃣引致肌少症的主要成因,包括缺乏運動的生活方式和營養不良。[7]
2️⃣年紀令肌肉機能弱化,不使用(遺棄 disuse)肌肉會加劇這個問題 [8]
3️⃣要點:長期不使用肌肉(chronic disuse),是肌肉量流失和力量下降最主要的成因,並非老化(aging) [6]
4️⃣年紀不影響肌肉對力量訓練的反應 [4]
5️⃣年輕和老年的女性有着差不多的肌肥大及力量增長 [5]
6️⃣年輕和老年的個體有著差不多的肌肥大增長 [3]
CrMenno Henselmanselmans
🔥🔥🔥
「年紀是心靈勝於物質的問題,如果你不在乎,就無所謂。」 Age is an issue of mind over matter. If you don't mind, it doesn't matter.
如有興趣深入了解各研究的背景,可以參閱Reference部份中的文章‼️
Reference
1. III, L.J.M., Khosla, S., Crowson, C.S., O'Connor, M.K., O'Fallon, W.M. and Riggs, B.L. (2000), Epidemiology of Sarcopenia. Journal of the American Geriatrics Society, 48: 625-630. https://doi.org/10.1111/j.1532-5415.2000.tb04719.x
2. Lowndes J, Carpenter RL, Zoeller RF, Seip RL, Moyna NM, Price TB, Clarkson PM, Gordon PM, Pescatello LS, Visich PS, Devaney JM, Gordish-Dressman H, Hoffman EP, Thompson PD, Angelopoulos TJ. Association of age with muscle size and strength before and after short-term resistance training in young adults. J Strength Cond Res. 2009 Oct;23(7):1915-20. doi: 10.1519/JSC.0b013e3181b94b35. PMID: 19749605; PMCID: PMC4103410.
3. Ivey FM, Roth SM, Ferrell RE, Tracy BL, Lemmer JT, Hurlbut DE, Martel GF, Siegel EL, Fozard JL, Jeffrey Metter E, Fleg JL, Hurley BF. Effects of age, gender, and myostatin genotype on the hypertrophic response to heavy resistance strength training. J Gerontol A Biol Sci Med Sci. 2000 Nov;55(11):M641-8. doi: 10.1093/gerona/55.11.m641. PMID: 11078093.
4. Mayhew DL, Kim JS, Cross JM, Ferrando AA, Bamman MM. Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans. J Appl Physiol (1985). 2009;107(5):1655-1662. doi:10.1152/japplphysiol.91234.2008
5. Loenneke, J.P., Rossow, L.M., Fahs, C.A., Thiebaud, R.S., Grant Mouser, J. and Bemben, M.G. (2017), Time‐course of muscle growth, and its relationship with muscle strength in both young and older women. Geriatr Gerontol Int, 17: 2000-2007. https://doi.org/10.1111/ggi.13010
6. Andrew P. Wroblewski, Francesca Amati, Mark A. Smiley, Bret Goodpaster & Vonda Wright (2011) Chronic Exercise Preserves Lean Muscle Mass in Masters Athletes, The Physician and Sportsmedicine, 39:3, 172-178, DOI: 10.3810/psm.2011.09.1933
7. Kim JS, Wilson JM, Lee SR. Dietary implications on mechanisms of sarcopenia: roles of protein, amino acids and antioxidants. J Nutr Biochem. 2010 Jan;21(1):1-13. doi: 10.1016/j.jnutbio.2009.06.014. Epub 2009 Oct 1. PMID: 19800212.
8. Venturelli M, Saggin P, Muti E, Naro F, Cancellara L, Toniolo L, Tarperi C, Calabria E, Richardson RS, Reggiani C, Schena F. In vivo and in vitro evidence that intrinsic upper- and lower-limb skeletal muscle function is unaffected by ageing and disuse in oldest-old humans. Acta Physiol (Oxf). 2015 Sep;215(1):58-71. doi: 10.1111/apha.12524. Epub 2015 May 28. PMID: 25965867; PMCID: PMC4516639.
9. Huebner M, Perperoglou A. Performance Development From Youth to Senior and Age of Peak Performance in Olympic Weightlifting. Front Physiol. 2019;10:1121. Published 2019 Aug 27. doi:10.3389/fphys.2019.01121
10. Age of Peak Competitive Performance of Elite Athletes: A Systematic Review
11. Peak Age and Performance Progression in World-Class Weightlifting and Powerlifting Athletes
額外閱讀:https://mennohenselmans.com/how-bad-is-aging-for-your-gains/
in vivo and in vitro 在 皮筋兒 Journey Facebook 的最讚貼文
在臉書河道看到的一篇文章,發文的人翻譯了一則外國人的發文:
https://m.facebook.com/story.php?story_fbid=10158846902129328&id=602809327
我有在外國人的發文底下留言,可惜不能在這個翻譯的人底下留言,所以我打在這邊。
首先 #疫苗 是什麼?這個google很容易,高中生物應該也有提過,疫苗的發展大約兩百年,前一百年只有不活化疫苗和減毒疫苗,後一百年才陸續研發了純化蛋白疫苗以及基因工程疫苗等等。
再來了解疫苗的分類:
#活疫苗 有不活化與減毒活疫苗、異質性活疫苗(例如牛痘)
#死疫苗 有死毒疫苗、死菌疫苗、次單位疫苗(細分 類毒素疫苗、基因工程重組蛋白疫苗、胜肽疫苗、基因轉殖植物性疫苗、基因型疫苗或抗基因型抗體)、多核苷或DNA疫苗、載體疫苗、標記疫苗、mRNA疫苗(近十年嶄新研究)。
(附上大學課本疫苗發展與實驗內頁比較圖)
基因疫苗自1992年首次在科學文獻報告至今,已經成為最熱門的疫苗研究新方向,目前包括傳染性疾病、癌症、過敏症與自體免疫性疾病,以廣泛進行基因疫苗的臨床前或臨床研究並獲得良好的結果。
發文的人顯然不懂疫苗有分活疫苗跟死疫苗,也不懂mRNA疫苗不等於活疫苗,應該也不懂免疫學。
這篇錯誤訊息蠻多的,可以參考國衛院的說明
https://forum.nhri.org.tw/covid19/j_translate/j2022/
當年大學學習時就知道了,疫苗的研發與應用的智慧,基因疫苗的作用原理與傳統疫苗不同。
傳統死毒疫苗或者重組蛋白疫苗,病毒抗原是由體外注射到人體,經由巨噬細胞等抗原呈現細胞(APC cell)吞噬後,被分解的抗原片段經MHC2(組織相容性複合體第二型)呈現給T cell。此種免疫反應是以引發輔助T cell,產生抗體為主的免疫反應。
而基因疫苗是在進入細胞後於細胞質表現抗原蛋白,這些內生性蛋白有部分會被酵素分解成蛋白片段,在內質網和MHC1結合以後呈現在細胞膜上,藉此和殺手T細胞表面受器結合,活化殺手T細胞,引發細胞毒殺作用。
基因疫苗也能引發MHC2抗體反應,因此基因疫苗可以同時引發抗體反應和殺手T細胞反應。
2018年發表的文獻指出mRNA疫苗的優點:
Over the past decade, major technological innovation and research investment have enabled mRNA to become a promising therapeutic tool in the fields of vaccine development and protein replacement therapy. The use of mRNA has several beneficial features over subunit, killed and live attenuated virus, as well as DNA-based vaccines. First, safety: as mRNA is a non-infectious, non-integrating platform, there is no potential risk of infection or insertional mutagenesis. Additionally, mRNA is degraded by normal cellular processes, and its in vivo half-life can be regulated through the use of various modifications and delivery methods. The inherent immunogenicity of the mRNA can be down-modulated to further increase the safety profile. Second, efficacy: various modifications make mRNA more stable and highly translatable. Efficient in vivo delivery can be achieved by formulating mRNA into carrier molecules, allowing rapid uptake and expression in the cytoplasm (reviewed in Refs 10,11). mRNA is the minimal genetic vector; therefore, anti-vector immunity is avoided, and mRNA vaccines can be administered repeatedly. Third, production: mRNA vaccines have the potential for rapid, inexpensive and scalable manufacturing, mainly owing to the high yields of in vitro transcription reactions.
1. 安全性,非感染性活體病毒,沒有潛在感染跟插入誘導基因改變的風險。
2. 穩定且可製成載體進入細胞質中,屬於最小的mRNA載體。(過往的基因疫苗都是需要plasmid DNA載體DNA,多一個步驟。)
3. 沒有抗載體的免疫反應,因此不用擔心anti-vector immunity。不會有過敏或者自體免疫產生。
4. 生產也很便利快速。
美國食品與藥物管理局特別針對基因疫苗的安全性、潛力與免疫能力制定相關規定,”Points to Consider on Plasmid DNA Vaccines for Preventive Infections Disease Indication”,作為研究基因疫苗時的參考指標。
相關文獻references:
1. Donnelly,J.J.,J.B. Ulmer, J.W. Shiver, and M.A. Liu. 1997. DNA vaccines. Annu. Rev. Immunol. 15:617-48.
2. Cytotoxic T-lymphocyte-, and helper T-lymphocyte-oriented DNA vaccination
Toshi Nagata et al. DNA Cell Biol. 2004 Feb.
https://pubmed.ncbi.nlm.nih.gov/15000749/
3. mRNA vaccines — a new era in vaccinology
https://www.nature.com/articles/nrd.2017.243
in vivo and in vitro 在 夠維根Go Vegan Youtube 的最佳解答
這是個常見的迷思,不只一般的民眾會搞混
連專業的醫療人員都不太清楚...
FB粉絲專頁:https://www.facebook.com/GoVeganTW
提倡一種新的生活態度,透過動畫宣導"動物權利"!
特別感謝"台灣素食營養學會"贊助
臺灣素食營養學會官網:http://www.twvns.org/
--------------------------------------------------------------------------------
【參考資料】
不吃肉蛋白質夠嗎?http://www.twvns.org/info/faq/25-2008-08-20-03-38-47
顛覆你的觀念!你真的知道怎麼吃蛋白質?: www.twvns.org/info/faq/266-2015-06-17-09-32-20
告訴你~痛風要吃黃豆的理由: www.twvns.org/info/faq/213-2015-04-17-07-41-12
乳癌不能吃黃豆? https://youtu.be/ie3pVBvnIEM
1. 每日蛋白質需求量:
http://www.nationalacademies.org/hmd/~/media/Files/Activity%20Files/Nutrition/DRIs/DRI_Macronutrients.pdf
2. 豆類的優點(預防疾病、營養素):
Messina V. Nutritional and health benefits of dried beans. Am J Clin Nutr. 2014 Jul;100 Suppl 1:437S-42S. doi: 10.3945/ajcn.113.071472. Epub 2014 May 28.
3. 痛風可以吃豆類:
Teng GG, Pan A, Yuan JM, Koh WP. Food Sources of Protein and Risk of Incident Gout in the Singapore Chinese Health Study. Arthritis Rheumatol. 2015 Jul;67(7):1933-42. doi: 10.1002/art.39115.
4. 美國痛風研究:
Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med. 2004 Mar 11;350(11):1093-103.
Messina M, Messina VL, Chan P. Soyfoods, hyperuricemia and gout: a review of the epidemiologic and clinical data. Asia Pac J Clin Nutr. 2011;20(3):347-58.Review.
5. 日本痛風研究:
Yamakita J, Yamamoto T, Moriwaki Y, Takahashi S, Tsutsumi Z, Higashino K. Effect of Tofu (bean curd) ingestion and on uric acid metabolism in healthy and gouty subjects. Adv Exp Med Biol. 1998;431:839-42.
6. 乳癌研究:
Caan BJ, Natarajan L, Parker B et al. (2011) Soy food consumption and breast cancer prognosis. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20, 854-858.
Doyle C, Kushi LH, Byers T et al. (2006) Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices. CA: a cancer journal for clinicians 56, 323-353.
Guha N, Kwan ML, Quesenberry CP, Jr. et al. (2009) Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study. Breast cancer research and treatment 118, 395-405.
Hsieh CY, Santell RC, Haslam SZ et al. (1998) Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer research 58, 3833-3838.
Rock CL, Doyle C, Demark-Wahnefried W et al. (2012) Nutrition and physical activity guidelines for cancer survivors. CA: a cancer journal for clinicians 62, 243-274.
Setchell KD, Brown NM, Zhao X et al. (2011) Soy isoflavone phase II metabolism differs between rodents and humans: implications for the effect on breast cancer risk. The American journal of clinical nutrition 94, 1284-1294.
Shu XO, Zheng Y, Cai H et al. (2009) Soy food intake and breast cancer survival. Jama 302, 2437-2443.
7.吃素節能減碳:
Ruini LF, Ciati R, Pratesi CA, Marino M, Principato L, Vannuzzi E. Working toward Healthy and Sustainable Diets: The "Double Pyramid Model" Developed by the Barilla Center for Food and Nutrition to Raise Awareness about the Environmental and Nutritional Impact of Foods. Front Nutr. 2015 May 4;29.