本文選題：甲型肝炎 + 疫苗　； 參考：《北京生物制品研究所》2007年碩士論文

【摘要】： 甲型肝炎疫苗在甲型肝炎的預(yù)防和控制中發(fā)揮了積極作用。目前，甲型肝炎全病毒滅活苗在國(guó)內(nèi)外已廣泛使用；甲型肝炎減毒苗在國(guó)內(nèi)也已得到廣泛使用。實(shí)驗(yàn)研究和臨床應(yīng)用效果顯示兩種疫苗均具有較好的免疫原性，其免疫接種后的抗體陽轉(zhuǎn)率、抗體滴度以及抗體保護(hù)的持久性等方面，已經(jīng)得到充分的肯定。近年來隨著對(duì)分子水平免疫反應(yīng)認(rèn)識(shí)的深入和基礎(chǔ)研究的不斷加強(qiáng)，以及方法學(xué)的進(jìn)一步發(fā)展，人們?cè)u(píng)價(jià)一種疫苗的免疫應(yīng)答效果，不再僅局限于體液免疫方面，而是越來越關(guān)注疫苗誘導(dǎo)的細(xì)胞免疫的重要作用。 本研究主要評(píng)價(jià)目前國(guó)內(nèi)普遍應(yīng)用的兩種甲肝疫苗，即甲肝減毒活疫苗與甲肝滅活疫苗，免疫接種后誘導(dǎo)的細(xì)胞免疫應(yīng)答效果以及兩者間差別，同時(shí)檢測(cè)甲肝抗體滴度和抗體陽轉(zhuǎn)率，探討細(xì)胞免疫與體液免疫的關(guān)系及細(xì)胞免疫在早期抗甲肝病毒感染保護(hù)中的作用。 我們從18～22歲的健康志愿者中，選擇甲肝總抗體陰性者和既往甲肝疫苗接種者共18人為本次研究對(duì)象。隨機(jī)分為4組，其中實(shí)驗(yàn)組分為2組，每組7人，分別接種甲肝減毒活疫苗和甲肝滅活疫苗；對(duì)照組中，設(shè)立陽性對(duì)照(既往有甲肝疫苗接種史，自愿加強(qiáng)一劑甲肝疫苗)和陰性對(duì)照(實(shí)驗(yàn)結(jié)束時(shí)，再接種甲肝疫苗)，每組2人。分別在0周(免疫接種前)和免疫接種后1周、2周、3周、4周、5周、6周、24周(6個(gè)月)、25周(滅活苗加強(qiáng)后1周)各采血一次，分離血清，以化學(xué)發(fā)光法對(duì)特異性甲肝抗體進(jìn)行定性和定量檢測(cè)；同時(shí)分離外周血單個(gè)核細(xì)胞PBMC，在體外將PBMC以特異性甲肝抗原刺激后，ELISPOT法檢測(cè)效應(yīng)T細(xì)胞分泌Th1型細(xì)胞因子IFN-γ、IL-2情況，胞內(nèi)染色法測(cè)定CD3／CD4~+T淋巴細(xì)胞、CD3／CD8~+T淋巴細(xì)胞中分泌IFN-γ的陽性細(xì)胞百分比，Luminex法檢測(cè)細(xì)胞培養(yǎng)上清中IFN-γ、IL-2、IL-10、IL-4等多種細(xì)胞因子水平。 實(shí)驗(yàn)數(shù)據(jù)提示，應(yīng)用ELISPOT、胞內(nèi)染色、Luminex等檢測(cè)方法，特異性好、靈敏度高，結(jié)果穩(wěn)定、可靠，適用于疫苗接種后特異性細(xì)胞免疫應(yīng)答的評(píng)價(jià)。實(shí)驗(yàn)結(jié)果顯示，在免疫接種甲肝滅活疫苗、甲肝減毒活疫苗后，，早期便可誘導(dǎo)產(chǎn)生病毒特異性T細(xì)胞的細(xì)胞免疫應(yīng)答反應(yīng)，并且伴隨高水平的效應(yīng)細(xì)胞因子IFN-γ產(chǎn)生。同時(shí)提示，在早期的某些時(shí)間點(diǎn)上，兩種苗所誘導(dǎo)的病毒特異性細(xì)胞免疫反應(yīng)強(qiáng)度存在差別，推測(cè)與兩種疫苗的甲肝抗原含量以及減毒苗活病毒在體內(nèi)復(fù)制增殖后產(chǎn)生大量?jī)?nèi)源性抗原有關(guān)。研究數(shù)據(jù)還顯示，加強(qiáng)接種后激發(fā)免疫記憶性在甲肝疫苗接種者是存在的。在病毒特異性T細(xì)胞增殖反應(yīng)的存在條件下，接種者受到病毒性抗原的刺激下會(huì)發(fā)生快速的免疫應(yīng)答反應(yīng)，結(jié)果導(dǎo)致快速高水平的抗體和IFN-γ等抗病毒細(xì)胞因子產(chǎn)生。 本研究初步建立了甲型肝炎疫苗的細(xì)胞免疫評(píng)價(jià)方法，通過對(duì)甲肝疫苗在人體免疫應(yīng)答效果的探討和分析，補(bǔ)充和完善了甲肝疫苗的免疫效果評(píng)價(jià)資料；通過人體誘導(dǎo)的細(xì)胞免疫的相關(guān)研究，填補(bǔ)了國(guó)內(nèi)外關(guān)于甲肝減毒活疫苗在人體誘導(dǎo)的細(xì)胞免疫相關(guān)研究的空缺，為今后更加全面的評(píng)價(jià)甲肝疫苗誘導(dǎo)的細(xì)胞免疫以及甲肝疫苗能否用于甲肝暴露后預(yù)防提供了一定的參考依據(jù)。
[Abstract]:Hepatitis A vaccine has played a positive role in the prevention and control of hepatitis A . At present , the inactivated vaccine of hepatitis A virus has been widely used at home and abroad ;
In recent years , with the deepening of the understanding of molecular level immune response , the increasing of antibody titer and the persistence of antibody protection , it has been fully affirmed that in recent years , with the deepening of the understanding of molecular level immune response and the persistence of antibody protection , it has been evaluated that the immune response of a vaccine is no longer limited to humoral immunity , but is more and more concerned with the important role of vaccine - induced cellular immunity .









In this study , two kinds of hepatitis A vaccine , namely hepatitis A live attenuated live vaccine and hepatitis A virus inactivated vaccine , were evaluated in this study . The cellular immune response effect induced after immunization and the difference between them were evaluated . Meanwhile , the relationship between antibody titer and antibody positive rate was detected , and the relationship between cellular immunity and humoral immunity and the role of cellular immunity in the protection of early hepatitis A virus infection were discussed .









In the healthy volunteers from 18 to 22 years of age , 18 were randomly divided into 4 groups , in which the experimental group was divided into 4 groups , in which the experimental group was divided into 2 groups , 7 in each group , respectively inoculated with hepatitis A virus attenuated live vaccine and hepatitis A inactivated vaccine ;
In the control group , positive control was established ( prior to vaccination history of hepatitis A vaccine , voluntary enhancement of a dose of hepatitis A vaccine ) and negative control ( at the end of the experiment ) , 2 persons in each group . After 0 weeks ( pre - vaccination ) and 1 week after immunization respectively , 2 weeks , 3 weeks , 4 weeks , 5 weeks , 6 weeks , 24 weeks ( 6 months ) , 25 weeks ( 1 week after inactivated vaccine ) , the serum was isolated , and the specific hepatitis A antibodies were qualitatively and quantitatively detected by chemiluminescence method ;
The levels of IFN - 緯 , IL - 2 , IL - 10 and IL - 4 were measured by Luminex method .









The results showed that after immunization with hepatitis A virus inactivated vaccine and hepatitis A virus attenuated live vaccine , the cell immune response of virus - specific T cells could be induced .









In this study , the cellular immunity evaluation method of hepatitis A vaccine was established , and the evaluation data of the immune response of hepatitis A vaccine was supplemented and improved by discussing and analyzing the effect of hepatitis A vaccine on human immune response .
The study of cell immunity induced by human body fills the vacancy of the research on cell immunity induced by hepatitis A attenuated live vaccine at home and abroad , and provides a certain reference for the future comprehensive evaluation of the cell immunity induced by hepatitis A vaccine and whether the hepatitis A vaccine can be used for preventing hepatitis A exposure .
【學(xué)位授予單位】：北京生物制品研究所
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2007
【分類號(hào)】：R392

【參考文獻(xiàn)】

相關(guān)期刊論文 前6條

1 馬景臣,韓常全,丁月新,劉洪斌,張勇,張英林,汪萱怡,張玉偉,邢占春,趙卉,孟宗達(dá),徐志一;甲型肝炎減毒活疫苗加強(qiáng)免疫的效果[J];中國(guó)生物制品學(xué)雜志;2003年01期

2 陳嘉,羅榮娟,徐婉顏,張金蓮,李玉珠;甲型肝炎滅活疫苗與減毒活疫苗的免疫效果觀察[J];預(yù)防醫(yī)學(xué)論壇;2005年02期

3 劉建生,徐冬蕾,孟明耀,龐偉,馬進(jìn),陳統(tǒng)球,侯宗柳;甲型肝炎滅活疫苗(L-8株)口服及腹腔注射Bal b/c小鼠的免疫反應(yīng)評(píng)價(jià)[J];中國(guó)計(jì)劃免疫;2005年02期

4 徐冬蕾,劉建生,孟明耀,龐偉,馬進(jìn),張鳴,陳統(tǒng)球,侯宗柳;甲型肝炎減毒活疫苗免疫小鼠后的體液和細(xì)胞免疫應(yīng)答[J];中華微生物學(xué)和免疫學(xué)雜志;2005年03期

5 汪萱怡,馬景臣,徐志一,劉洪斌,張英林,韓常全,張玉偉,邢占春,陳吉朝,孟宗達(dá),顧惠心;甲型肝炎減毒活疫苗暴露后預(yù)防效果的觀察[J];中華醫(yī)學(xué)雜志;2002年14期

6 徐志一,李榮成,孟宗達(dá),張勇,閻純楷,周廷魁,汪萱怡,龔健,李艷萍,江世平,黃全誠(chéng),趙玉良,馬景臣,史同深,劉新立,夏建玲,李燕婷,劉洪斌,歐陽佩英;甲型肝炎減毒活疫苗免疫原性和保護(hù)效果的初步觀察[J];中華醫(yī)學(xué)雜志;1998年04期

本文編號(hào)：2016381