B型肝炎疫苗 Hepatitis B vaccine
編輯歷史
| 時間 | 作者 | 版本 |
|---|---|---|
| 2017-07-17 16:32 – 16:33 | r0 – r1 | |
顯示 diff+ B型肝炎疫苗 Hepatitis B vaccine
+
+ 英文條目:https://en.wikipedia.org/wiki/Hepatitis_B_vaccine
+
+ 中文條目https://zh.wikipedia.org/wiki/%E4%B9%99%E5%9E%8B%E8%82%9D%E7%82%8E%E7%96%AB%E8%8B%97
+ （內容為 "B型肝炎疫苗（英語：Hepatitis B vaccine），或稱B肝疫苗是一種用來預防由B肝病毒導致的B型肝炎的疫苗。"）
+
+ Hepatitis B vaccine is a vaccine that prevents hepatitis B.[1] The first dose is recommended within 24 hours of birth with either two or three more doses given after that. This includes those with poor immune function such as from HIV/AIDSand those born premature. In healthy people routine immunization results in more than 95% of people being protected.[1]
+ Blood testing to verify that the vaccine has worked is recommended in those at high risk. Additional doses may be needed in people with poor immune function but are not necessary for most people. In those who have been exposed to thehepatitis B virus but not immunized, hepatitis B immune globulin should be given in addition to the vaccine. The vaccine is given by injection into a muscle.[1]
+
+ '''B型肝炎疫苗'''（{{lang|en|Hepatitis B vaccine}}），常簡稱'''B肝疫苗'''。是用來預防[[B型肝炎]]的[[疫苗]][1] 。第一劑建議於出生後的24小時內就注射，要視情況決定之後還須追加第二或第三劑。這包括[[免疫功能不全]]的患者例如：患有[[人類免疫缺乏病毒]]或[[早產兒]]。若是身心健康且有定期接種疫苗，則保護力可高達95% [1]。
+ 高風險族群會建議進行血液檢測以確認疫苗的效用。有免疫功能問題的病人可能有追加注射疫苗的必要，但一般民眾則大多不需要。曾受到[[B型肝炎病毒]]感染且尚未有健全免疫力的病患，之後追加施打的疫苗應增加{{le|B型肝炎免疫球蛋白|Hepatitis B immune globulin}}，此疫苗會經由{{le|肌肉注射|Intramuscular injection}}的方式接種[1]。
+
+ Serious side effects from the hepatitis B vaccine are very uncommon. Pain may occur at the site of injection. It is safe for use during pregnancy or while breastfeeding. It has not been linked to Guillain-Barre syndrome. The current vaccines are produced with recombinant DNA techniques. They are available both by themselves and in combination with other vaccines.[1]
+ B型肝炎疫苗較少會引發嚴重的副作用，在注射的當下可能會感到些許疼痛。在[[懷孕]]或是[[哺乳期間]]依舊可以施打疫苗。並沒有證據顯示B肝疫苗和[[格林-巴利症候群]]有相關性。現今使用的疫苗是利用[[DNA重組技術]]製成的，可以單獨使用或和其他疫苗混合施打[1]。
+
+ The first hepatitis B vaccine was approved in the United States in 1981.[2] A safer version came to market in 1986.[1] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[3] The wholesale cost is between 0.58 and 13.20 USD per dose as of 2014.[4] In the United States it costs between 50 and 100 USD.[5]
+ 第一劑的B肝疫苗是在1981年經美國核准[2]，1986年一個更加安全的疫苗接著問世[1]。目前此藥名列[[世界衛生組織基本藥物標準清單]]內，同時也是[[基礎醫療]]裡很重要的藥物之一[3] 。2014年單劑的量販價介於0.58至13.20美元間[4]，在美國的售價則落在50到100美元的區間內[5]。
+
+
+ *Medical uses（醫療用途）
+
+ Babies born to mothers infected with HBV are vaccinated with hepatitis B vaccine and injected with hepatitis B immunoglobulin (HBIG).[6]
+
+ 若母親為B型肝炎帶原者，嬰兒會在出生24小時內[中1]接種B型肝炎疫苗，並注射B型肝炎免疫球蛋白（HBIG）[6]，若出生後臨床狀況穩定則越早注射越好[中1]。
+
+ *[中1]http://www.cdc.gov.tw/professional/info.aspx?treeid=5b0231beb94edffc&nowtreeid=dc132e275cf714e3&tid=D76D08D4B13EB623
+
+ Many countries now routinely vaccinate infants against hepatitis B. In countries with high rates of hepatitis B infection, vaccination of newborns has not only reduced the risk of infection, but has also led to marked reduction in liver cancer. This was reported in Taiwan where the implementation of a nationwide hepatitis B vaccination program in 1984 was associated with a decline in the incidence of childhood hepatocellular carcinoma.[7]
+ 現今很多國家注射疫苗以對付B型肝炎。有很多國家B型肝炎感染的機率較高，新生兒接種B型肝炎疫苗不只可以降低感染的風險，也顯著的減少了[[肝癌]]的病例。像[[台灣]]1984年實施的B型肝炎接種計劃也和其兒童肝癌發生率的下降有關[7][中2]。
+
+ *[中2] <ref>[http://www.tccf.org.tw/old/magazine/vol7/8.htm B型肝炎疫苗接種與盛行率之下降]</ref>
+
+ In UK, the vaccine is offered to MSM, usually as part of a sexual health check-up. A similar situation is in operation in Ireland.[8]
+
+ 在英國，會提供B型肝炎疫苗給[[男男性接觸人群]]，這是性健康檢查的一部分，在愛爾蘭也有類似的措施[8]。
+
+ In many areas, vaccination against hepatitis B is also required for all health-care and l
+ aboratory staff.[9]
+
+ 在許多地區，所有醫療護理人員及相關實驗室人員都要接受B型肝炎疫苗接種[9]。
+
+ The Centers for Disease Control and Prevention have issued recommendations for vaccination against hepatitis B among patients with diabetes mellitus.[10]
+
+ [[美国疾病控制与预防中心]]建議[[糖尿病]]病患都接受B型肝炎疫苗接種[10]。
+
+ Effectiveness(疫苗效用)
+
+ Following the primary course of 3 vaccinations, a blood test may be taken after an interval of 1–4 months to establish if there has been an adequate response, which is defined as an anti-hepatitis B surface antigen antibody level above 100 mIU/ml. Such a full response occurs in about 85–90% of individuals.[11]
+
+ 在首次完成三劑B型肝炎疫苗注射後一到四個月會抽一次血，檢驗B型肝炎表面抗原B型肝炎病毒表面抗體（anti-hepatitis B surface antigen antibody(anti-Hbs)）的數值是否超過100 mIU/ml，超過則代表個體對疫苗已經產生適當的免疫反應，通常百分之85到90的人注射完疫苗後會產生反應。
+ *原文中 anti-hepatitis B surface antigen (anti-Hbs) antibody level 應該是b型肝炎表面抗原的抗體，(anti-Hbs)也是''表面抗原的抗體''的縮寫，所以我把括弧移到antibody之後
+
+ *補充:表面抗原陽性就是感染，表示有病毒才會驗到病毒表面抗原，打疫苗是為了發展出表面抗原的抗體，也就是免疫力，所以抗體陽性是有免疫力，沒打過的人有抗體那就是被感染過
+
+ *翻譯怕混淆，在台灣都不翻''B型肝炎表面抗原抗體''，都翻成''B型肝炎表面抗體''
+ *http://www.cdc.gov.tw/professional/knowdisease.aspx?treeid=BEAC9C103DF952C4&nowtreeid=7296679902209942&id=4632148C425C4923&did=656
+
+ An antibody level between 10 and 100 mIU/ml is considered a poor response, and these people should receive a single booster vaccination at this time, but do not need further retesting.[11]
+
+ B型肝炎表面抗體數值介在10 到 100 mIU/ml 之間視為對疫苗反應不佳，這些人需要在檢驗出來後再額外注射一劑疫苗，但不需要隔一段時間後再抽血評估。
+
+
+ People who fail to respond (anti-Hbs antibody level below 10 mIU/ml) should be tested to exclude current or past Hepatitis B infection, and given a repeat course of 3 vaccinations, followed by further retesting 1–4 months after the second course. Those who still do not respond to a second course of vaccination may respond to intradermal administration[12] or to a high dose vaccine[13] or to a double dose of a combined Hepatitis A and B vaccine.[14] Those who still fail to respond will require hepatitis B immunoglobulin (HBIG) if later exposed to the hepatitis B virus.[11]
+
+ B型肝炎表面抗體數值落在10 mIU/ml以內表示個體對疫苗不反應，這些人在抽血檢查以排除是否過去曾感染B肝或現在正處於感染階段，並且接受額外三劑B型肝炎疫苗注射，注射完成後經一到四個月再抽血檢測B型肝炎表面抗體數值。那些在第二次疫苗注射療程後依舊對疫苗沒有反應的人，可能會對皮內注射、高劑量疫苗，或是A型B型肝炎結合疫苗有反應，而對疫苗依舊沒有反應的人如果之後暴露到B型肝炎病毒，會需要注射B型肝炎免疫球蛋白（HBIG）。
+
+ Poor responses are mostly associated with being over the age of 40 years, obesity and smoking,[15] and also in alcoholics, especially if with advanced liver disease.[16]Patients who are immunosuppressed or on renal dialysis may respond less well and require larger or more frequent doses of vaccine.[11] At least one study suggests that hepatitis B vaccination is less effective in patients with HIV.[17]
+
+ 對疫苗反應不佳的人通常是因為以下因素 : 超過40歲、肥胖、抽菸或酗酒，尤其是有嚴重肝病患者。 免疫抑制的病人或接受腎臟透析的病人也可能對疫苗反應較差或需要更大劑量、頻率的疫苗注射。至少已有一個研究指出，B型肝炎的疫苗在HIV患者體內較難生效。
+
+ Duration of protection(疫苗保護期)
+
+ It is now believed that the hepatitis B vaccine provides indefinite protection. However, it was previously believed and suggested that the vaccination would only provide effective cover of between five and seven years,[18][19] but subsequently it has been appreciated that long-term immunity derives from immunological memory which outlasts the loss of antibody levels and hence subsequent testing and administration of booster doses is not required in successfully vaccinated immunocompetent individuals.[20][21] Hence with the passage of time and longer experience, protection has been shown for at least 25 years in those who showed an adequate initial response to the primary course of vaccinations,[22] and UK guidelines now suggest that for initial responders who require ongoing protection, such as for healthcare workers, only a single booster is advocated at 5 years.[11]
+
+ 目前認為疫苗只能提供五到七年的免疫保護[18][19]，但隨後發現人體{{le|免疫記憶功能|immunological memory}}會發展出長期免疫。長期免疫會長久維持而不受體內抗體減少的影響，因此在疫苗成功建立對B型肝炎病毒免疫功能的個體中，終生不需要再做抗體數值追蹤及補打疫苗[20][21]。在長期實驗中，那些施打疫苗一開始即有適當抗體數量的個體，疫苗保護力至少維持25年。英國的指導方針建議對於需要持續保護力的人群，例如醫藥衛生工作者，至少每五年施打一劑疫苗。
+
+ *這一段講的根本前後矛盾阿XD 抗體不會消失幹嘛補打
+ *以我臨床看到的是抗體體樹真的會隨時間衰退，有些人甚至一兩年就沒抗體了，上大學大家都會再測一次，DATA大概是經過20年有1/3左右人需要補打。
+
+ *Side effects（副作用）
+
+ Several studies looked for a significant association between recombinant hepatitis B vaccine (HBV) and multiple sclerosis (MS) in adults. Most published scientific studies do not support a causal relationship between hepatitis B vaccination and demyelinating diseases such as MS.[23] A 2004 study[24] reported a significant increase in risk within 3 years of vaccination. Some of these studies were criticized for methodological problems. This controversy created public misgivings about HB vaccination, and hepatitis B vaccination in children remained low in several countries. A 2006 study concluded that evidence did not support an association between HB vaccination and sudden infant death syndrome, chronic fatigue syndrome, or multiple sclerosis.[25] A 2007 study found that the vaccination does not seem to increase the risk of a first episode of MS in childhood.[26]
+ 近來有多項研究聚焦在觀察成人施打重組B型肝炎疫苗（HBV）與[[多發性硬化症]]（MS）間的關連。大部分已發表的科學研究多數都不認為B型肝炎疫苗和脫髓鞘疾病（如：多發性硬化症）有任何關係[23] 。只有一篇發表於2004年的研究顯示，在注射疫苗後的三年內，發病的機率有顯著提昇[24]。這當中有部分研究所採用的方法是飽受批評的。而這樣的爭議也誤導大眾對於注射B肝疫苗的想法，在少數幾個國家，孩童中有施打B肝疫苗的人數依舊偏低。2006年的另一篇研究得出的結論是，並沒有任何證據證明B肝疫苗和嬰兒猝死症、慢性疲勞症候群或是多發性硬化症之間有任何關係[25] 。於2007年公佈的研究認為，B肝疫苗並不會增加幼童時期罹患初期多發性硬化症的風險[26]。
+
+ A 2009 study of the hepatitis B vaccine and associated risk of CNS inflammatory demyelination was conducted. The hepatitis B vaccine was found to be generally safe, however the Engerix B vaccine appeared to triple the risk of CNS inflammatory demyelination in infant boys.[27] The study was criticized for methodological errors.[28]
+ The World Health Organization recommends a pentavalent vaccine, combining vaccines against diphtheria, tetanus, pertussis and Haemophilus influenzae type B with the vaccine against hepatitis B. There is not yet sufficient evidence on how effective this pentavalent vaccine is in relation to the individual vaccines.[29]
+ 2009年有一項研究針對B型肝炎疫苗和中樞神經炎症性[[脱髓鞘病]]間的關係進行研究，發現B型肝炎疫苗其實是相對安全的，真正有疑慮的是安在時（Engerix B vaccine）疫苗似乎會增加男嬰罹患中樞神經炎症性脱髓鞘病的風險，且高達三倍之多[27] 。但該研究也被批評，所用的研究方法尚有待商榷[28]。[[世界衛生組織]]建議使用五價疫苗，並混合[[白喉]]、[[破傷風]]、[[百日咳]]與[[B型流感嗜血菌]]的疫苗共同使用來對抗B型肝炎。現階段還缺乏決定性的證據，來了解到底五價疫苗和其他這些疫苗的共同作用或是關係[29]。
+
+ *History（歷史）
+
+ The road to the hepatitis B vaccine began in 1963 when American physician/geneticist Baruch Blumberg discovered what he called the "Australia Antigen" (now calledHBsAg) in the serum of an Australian Aboriginal person.[30] In 1968, this protein was found to be part of the virus that causes "serum hepatitis" (hepatitis B) by virologistAlfred Prince.[31] The American microbiologist/vaccinologist Maurice Hilleman at Merck used three treatments (pepsin, urea and formaldehyde) of blood serum together with rigorous filtration to yield a product that could be used as a safe vaccine.
+
+ Hilleman hypothesized that he could make an HBV vaccine by injecting patients with hepatitis B surface protein. In theory, this would be very safe, as these excess surface proteins lacked infectious viral DNA. The immune system, recognizing the surface proteins as foreign, would manufacture specially shaped antibodies, custom-made to bind to, and destroy, these proteins. Then, in the future, if the patient were infected with HBV, the immune system could promptly deploy protective antibodies, destroying the viruses before they could do any harm.[32]
+
+ B型肝炎疫苗的開發是在1963年開始的，當時澳洲醫師及遺傳學家[[巴鲁克·塞缪尔·布隆伯格]] 發現在[[澳大利亚原住民]]的血漿含有他稱為 "澳洲抗原"（現在的{{le|B肝表面抗原|HBsAg}}）[30]。1968年時，病毒學家{{le|阿爾弗雷德·卜林斯|Alfred Prince}}發現此蛋白質是導致"血清型肝炎"（B型肝炎）病毒的一部份[31]。美國[[默克藥廠]]的微生物家/疫苗學家{{le|莫里斯·希勒曼|Maurice Hilleman}}將血清和[[胃蛋白酶]]、[[尿素]]及[[甲醛]]混合後再過濾，得到的產物可以作安全的疫苗。希勒曼推測他可以將B肝表面蛋白質注射到病患體內作為疫苗。在理論上這相當安全，因為這些多餘的表面蛋白缺乏感染性病毒的DNA。免疫系統會識別這些蛋白質是外來物質，因此會產生特定形狀，可和蛋白質結合的抗體，用來摧毀這些蛋白質。因此以後若病患感染了B型肝炎，免疫系統可以及時產生保護性抗體，在病毒對人體有不良影響之前就破壞病毒[32]。
+ .
+ 希勒曼收集同性戀男性及[[娛樂性藥物]]使用者（已知較容易得到{{le|病毒性肝炎|viral hepatitis}}族群）的血液，當時是1970年代末期，當時醫學界還不知道HIV。血液樣本中除了B肝表面蛋白外，可能也包括HIV。希勒曼設計了一個有許多步驟的製程來純化血液，使其中只包括B肝表面蛋白。使製程消滅了其中所有當時已知的病毒，希勒曼相信此疫苗是安全的[32]。
+
+ The first large-scale trials for the blood-derived vaccine were performed on gay men, in accordance with their high-risk status. Later, Hilleman’s vaccine was falsely blamed for igniting the AIDS epidemic. (See Wolf Szmuness) But, although the purified blood vaccine seemed questionable, it was determined to have indeed been free of HIV. The purification process had destroyed all viruses—including HIV.[32] The vaccine was approved in 1981.
+ The blood-derived hepatitis B vaccine was withdrawn from the marketplace in 1986 when Pablo DT Valenzuela, Research Director of Chiron Corporation, succeeded in making the antigen in yeast and invented the world's first recombinant vaccine.[33] The recombinant vaccine was developed by inserting the HBV gene that codes for the surface protein into the yeast Saccharomyces cerevisiae. This allows the yeast to produce only the noninfectious surface protein, without any danger of introducing actual viral DNA into the final product.[32] This is the vaccine still in use today.
+
+ 用血液製成B肝疫苗進行的首次大規模臨床試驗，是以男同性戀者作為研究對象，以對應他們所處在的高風險狀態。之後希勒曼的疫苗卻被誤認為引燃愛滋病散播的元兇，因此受到抨擊。雖然純化血液所取得的疫苗看起來十分可疑，但它卻的確絕對不含愛滋病毒。疫苗純化的過程已經消滅了所有的病毒--包含愛滋病毒在內[32]，此疫苗也在1981年合法上市。
+
+ 1986年時{{le|奇龍公司|Chiron Corporation}}的研發經理成功的將B型肝炎抗原放進酵母中，製成了世界上第一劑重組疫苗，由血液製成的B型肝炎疫苗也退出巿場[33]。重組疫苗的作法是將產生表面蛋白的基因放進[[釀酒酵母]]中，因此酵母只會產生不具感染性的表面蛋白，疫苗中不會有真正病菌的DNA[32]，此B型肝炎疫苗目前仍在使用。
+
+
+ In 1976, Blumberg had won the Nobel Prize in Physiology or Medicine for his work on hepatitis B (sharing it with Daniel Carleton Gajdusek for his work on kuru). In 2002, Blumberg published a book, Hepatitis B: The Hunt for a Killer Virus.[34] In the book, according to Paul A. Offit—Hilleman's biographer and an accomplished vaccinologist himself—Blumberg...
+ ... claimed that the hepatitis B vaccine was his invention. Maurice Hilleman's name is mentioned once.... Blumberg failed to mention that it was Hilleman who had figured out how to inactivate hepatitis B virus, how to kill all other possible contaminating viruses, how to completely remove every other protein found in human blood, and how to do all of this while retaining the structural integrity of the surface protein. Blumberg had identified Australia antigen, an important first step. But all of the other steps—the ones critical to making a vaccine—belonged to Hilleman. Later, Hilleman recalled, "I think that [Blumberg] deserves a lot of credit, but he doesn't want to give credit to the other guy."[35]
+
+ 1976年，[[巴鲁克·塞缪尔·布隆伯格]]因為在B型肝炎的貢獻，和[[丹尼尔·卡尔顿·盖杜谢克]]（因[[庫魯病]]上的貢獻）一起獲得[[諾貝爾醫學獎]]。2002年布隆伯格出版了《''Hepatitis B: The Hunt for a Killer Virus''》。依照{{le|保羅·奧菲特|Paul A. Offit}}－撰寫希勒曼傳記的人，也是希勒曼熟識的疫苗學家－的說法，布隆伯格：
+
+ "聲稱B型肝炎疫苗是他的貢獻，希勒曼的名字只提到了一次。布隆伯格沒有提到希勒曼才知道如何使B型肝炎病毒去活化，如何殺死其他污染的病毒、如何完全去除血液中其他的蛋白質，又維持表面蛋白的結構完整。布隆伯格識別出了澳洲抗原，這是很重要的第一步，但後面的這幾步（也是疫苗製造的關鍵）是希勒曼完成的。最後希勒曼提到：「我認為他（布隆伯格）有很大的功勞，可是他不認為其他人也有功勞。」[35]
+
+
+ *Manufacture（製造）
+
+ The vaccine contains one of the viral envelope proteins, hepatitis B surface antigen (HBsAg). It now produced by yeast cells, into which the genetic code for HBsAg has been inserted.[36] Afterward an immune system antibody to HBsAg is established in the bloodstream. The antibody is known as anti-HBs. This antibody and immune system memory then provide immunity to HBV infection.[37]
+
+ 疫苗包括一種病毒包膜蛋白，也就是B肝表面蛋白（HBsAg），目前是基改過，可以產生B肝表面蛋白的酵母製造[36]。之後免疫系統會產生B肝表面蛋白的抗體（anti-HB），抗體及免疫系統的記憶性讓人體可以對抗B型肝炎[37]。
+
+
+ Brandnames（商品名）
+
+ The common brands available are Recombivax HB (Merck), Engerix-B (GSK), Elovac B (Human Biologicals Institute, a division of Indian Immunologicals Limited),Genevac B (Serum Institute), Shanvac B, etc. These vaccines are given by the intramuscular route.
+
+ 目前常見的商品名有 ''Recombivax HB'' （默克藥廠）、''Engerix-B''（GSK）、''Elovac B'' （Human Biologicals Institute，Indian Immunologicals Limited的子公司）、''Genevac B ''（Serum Institute）、''Shanvac B''等等。這些疫苗都是經肌肉注射。
+
+ *Research（研究）
+
+ Injectable Hepatitis B vaccines require expensive production processes and refrigeration, which can make them difficult to access in developing countries. As a result, researchers have been working to engineer plants capable of producing the ingredients necessary to make vaccines so that people can eat these plants to receive the vaccine. Potatoes, bananas, lettuce, carrots, tobacco are some of the plants being genetically engineered to produce the Hepatitis B vaccine ingredients.
+ 因為針劑型的B型肝炎疫苗之製成與冷凍程序所費不貲，這使得此疫苗在開發中國家較不普及。有鑑於此，研究者已經開始進行生物工程研究，希望可以找出製作疫苗內所需成分的植物，日後人們只要藉著食用該植物就可得到如同接種疫苗的效果。馬鈴薯、香蕉、萵苣、胡蘿蔔以及煙草等植物都藉由基因工程改造來製作B肝疫苗的組成成分。
+
+ The process of genetically engineering plants to produce the vaccine includes extracting the gene that codes for Hepatitis B surface antigens from the Hepatitis B genome, and placing it in a bacterial plasmid. The bacteria then infect a plant, which will produce the surface antigens. When a human eats the plant, their body is stimulated to produce an antibody response to the surface antigens. Although concerns remain in improving the efficacy of edible vaccines, controlling the dosage of vaccine in each plant, and managing land allocation for this process, scientists consider this a promising avenue for vaccinating underprivileged areas of the world.
+ 要製作疫苗所需的基因工程植物之製成程序包括；從B型肝炎的基因組中解讀出B型肝炎表面抗原的組成密碼，並以新的細菌質體取代之。該細菌會感染植物，接著再製造出表面抗原。當人們吃下植物後，身體就會自動產生對應表面抗原的抗體。現階段，可食用疫苗的功效仍有待提昇，而且每株植物的疫苗劑量更須調控，再來就是培育過程中土地的分配管控，但縱使有以上種種問題，科學家們依舊認為這對於讓B肝疫苗在相對落後國家的普及是一大福音。
+ *References
+ *1. "Hepatitis B vaccines WHO position paper" (PDF). Weekly epidemiological record 40 (84): 405–420. 2 Oct 2009.
+ *2. Moticka, Edward. A Historical Perspective on Evidence-Based Immunology. p. 336. ISBN 9780123983756.
+ *3. "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
+ *4. "Vaccine, Hepatitis B". International Drug Price Indicator Guide. Retrieved6 December 2015.
+ *5. Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 314. ISBN 9781284057560.
+ *6. Mast, E. E.; Margolis, H. S.; Fiore, A. E.; Brink, E. W.; Goldstein, S. T.; Wang, S. A.; Moyer, L. A.; Bell, B. P.; Alter, M. J.; Advisory Committee on Immunization Practices (ACIP) (2005). "A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents" (Free full text). MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control 54 (RR–16): 1–31. PMID 16371945.
+ *7. Chang, M. -H.; Chen, C. -J.; Lai, M. -S.; Hsu, H. -M.; Wu, T. -C.; Kong, M. -S.; Liang, D. -C.; Shau, W. -Y.; Chen, D. -S. (1997). "Universal Hepatitis B Vaccination in Taiwan and the Incidence of Hepatocellular Carcinoma in Children". New England Journal of Medicine 336 (26): 1855–1859. doi:10.1056/NEJM199706263362602.PMID 9197213.
+ *8. "Hepatitis B vaccine". www.nhs.uk.
+ *9. Joint Committee on Vaccination and Immunisation (2006). "Chapter 12 Immunisation of healthcare and laboratory staff—Hepatitis B". Immunisation Against Infectious Disease 2006 ("The Green Book") (PDF) (3rd ed.). Edinburgh: Stationery Office. p. 468. ISBN 0-11-322528-8.
+ *10. Centers for Disease Control and Prevention (CDC) (2011). "Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP).". MMWR Morb Mortal Wkly Rep 60(50): 1709–11. PMID 22189894.
+ *11. Joint Committee on Vaccination and Immunisation (2006). "Chapter 18 Hepatitis B". Immunisation Against Infectious Disease 2006 ("The Green Book")(PDF) (3rd edition (Chapter 18 revised 10 October 2007) ed.). Edinburgh: Stationery Office. p. 468. ISBN 0-11-322528-8.
+ *12. King; Taylor, E. M.; Crow, S. D.; White, M. C.; Todd, J. R.; Poe, M. B.; Conrad, S. A.; Gelder, F. B. (1990). "Comparison of the immunogenicity of hepatitis B vaccine administered intradermally and intramuscularly". Reviews of infectious diseases 12(6): 1035–1043. doi:10.1093/clinids/12.6.1035. PMID 2148433.
+ *13. Levitz; Cooper, B.; Regan, H. (1995). "Immunization with high-dose intradermal recombinant hepatitis B vaccine in healthcare workers who failed to respond to intramuscular vaccination". Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America 16 (2): 88–91.doi:10.1086/647062. PMID 7759824.
+ *14. Cardell, K.; Åkerlind, B.; Sällberg, M.; Frydén, A. (2008). "Excellent Response Rate to a Double Dose of the Combined Hepatitis a and B Vaccine in Previous Nonresponders to Hepatitis B Vaccine". The Journal of Infectious Diseases 198 (3): 299–226. doi:10.1086/589722. PMID 18544037.
+ *15. Roome, A. J.; Walsh, S.; Cartter, M.; Hadler, J. (1993). "Hepatitis B vaccine responsiveness in Connecticut public safety personnel". Journal of the American Medical Association 270 (24): 2931–2934. doi:10.1001/jama.270.24.2931.PMID 8254852.
+ *16. Rosman, Md, A.; Basu, P.; Galvin, K.; Lieber, C. (1997). "Efficacy of a High and Accelerated Dose of Hepatitis B Vaccine in Alcoholic Patients a Randomized Clinical Trial". The American Journal of Medicine 103 (3): 217–222. doi:10.1016/S0002-9343(97)00132-0. PMID 9316554.
+ *17.Pasricha, N.; Datta, U.; Chawla, Y.; Singh, S.; Arora, S.; Sud, A.; Minz, R.; Saikia, B.; Singh, H.; James, I.; Sehgal, S. (2006). "Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine". BMC Infectious Diseases 6: 65. doi:10.1186/1471-2334-6-65. PMC 1525180.PMID 16571140. Cold or Flu like symptoms can develop after receiving the vaccine, but these are short lived. As with any injection, the muscle can become tender around the injection point for some time afterwards
+ *18.Krugman; Davidson, M. (1987). "Hepatitis B vaccine: prospects for duration of immunity". The Yale journal of biology and medicine 60 (4): 333–339.PMC 2590237. PMID 3660859.
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+ *20. Gabbuti, A.; Romanò, L.; Blanc, P.; Meacci, F.; Amendola, A.; Mele, A.; Mazzotta, F.; Zanetti, A. R. (2007). "Long-term immunogenicity of hepatitis B vaccination in a cohort of Italian healthy adolescents". Vaccine 25 (16): 3129–3132.doi:10.1016/j.vaccine.2007.01.045. PMID 17291637.
+ *21. "Are booster immunisations needed for lifelong hepatitis B immunity?". The Lancet355 (9203): 561–565. 2000. doi:10.1016/S0140-6736(99)07239-6.PMID 10683019.
+ *22. Van Damme P, Van Herck K (March 2007). "A review of the long-term protection after hepatitis A and B vaccination". Travel Med Infect Dis 5 (2): 79–84.doi:10.1016/j.tmaid.2006.04.004. PMID 17298912.
+ *23."CDC - Hepatitis B and Multiple Sclerosis ( MS) - Vaccine Safety". cdc.gov.
+ *24.Hernán; Jick, S. S.; Olek, M. J.; Jick, H. (2004). "Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study". Neurology 63 (5): 838–842.doi:10.1212/01.WNL.0000138433.61870.82. PMID 15365133.
+ *25. Zuckerman, J. N. (2006). "Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines". Journal of Medical Virology 78 (2): 169–177.doi:10.1002/jmv.20524. PMID 16372285.
+ *26. Mikaeloff, Y.; Caridade, G.; Rossier, M.; Suissa, S.; Tardieu, M. (2007). "Hepatitis B Vaccination and the Risk of Childhood-Onset Multiple Sclerosis". Archives of Pediatrics & Adolescent Medicine 161 (12): 1176–1182.doi:10.1001/archpedi.161.12.1176. PMID 18056563.
+ *27. "Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood". Neurology. 2009.
+ *28. "Global Advisory Committee on Vaccine Safety: response to the paper (in press) by Y. Mikaeloff and colleagues in Neurology entitled "Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood"". World Health Organization. 2008.
+ *29. Bar-On ES, Goldberg E, Hellmann S, Leibovici L (2012). "Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB)". Cochrane Database Syst Rev (4): CD005530.doi:10.1002/14651858.CD005530.pub3. PMID 22513932.
+ *30. Blumberg B, Alter H (1965). "A "new" antigen in leukemia sera". JAMA 191: 101–106. doi:10.1001/jama.1965.03080070025007. PMID 14239025.
+ *31. Howard, Colin; Zuckerman, Arie J. (1979). Hepatitis viruses of man. Boston: Academic Press. pp. 16–18. ISBN 0-12-782150-3.
+ *32. "World Hepatitis Day: The History of the Hepatitis B Vaccine" [Planned Parenthood Advocates of Arizona], 26 July 2012,http://blog.advocatesaz.org/2012/07/26/world-hepatitis-day-the-history-of-the-hepatitis-b-vaccine/
+ *33. Fisher, Lawrence M. (October 13, 1986). "Biotechnology Spotlight Now Shines On Chiron". New York Times.
+ *34. Blumberg, Baruch (2002), Hepatitis B: The Hunt for a Killer Virus, Princeton: Princeton University Press.
+ *35. Offit, Paul A. (2007). Vaccinated:One Man's Quest to Defeat the World's Deadliest Diseases. New York: Smithsonian Books/Collins, pp 135-136..
+ *36."Hepatitis B Vaccine from Merck". Retrieved 2010-05-09.
+ *37. "CDC Viral Hepatitis". Atlanta, Georgia: Centers for Disease Control and Prevention. 2009-07-24. Retrieved 2009-10-22.
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