携带H7HA重组腺病毒载体流感疫苗在小鼠模型中免疫原性及交叉反应性的研究

发布时间：2018-04-08 10:00

本文选题：H7N9　切入点：流感病毒　出处：《安徽大学》2014年硕士论文

【摘要】：2013年3月底H7N9型流感病毒首次感染人类,机体缺乏针对H7N9的特异性保护抗体,疫苗是预防H7N9病毒在人群中传播的有效手段。研究表明H7N7(A/Netherlands/219/03)亚型灭活流感疫苗的免疫原性较低,通过提高抗原量、配合佐剂、多次免疫等多种方法才能得到理想的免疫效果。而目前H7N9流感病毒的免疫原性仍然未知。复制缺陷型腺病毒载体具有快速、安全性好、能激发较强的体液和细胞免疫反应等特点,且有研究表明携带H5HA的重组腺病毒载体流感疫苗能产生较灭活疫苗更高的中和抗体滴度和交叉保护活性。在本研究中,为了比较H7重组腺病毒疫苗和全病毒灭活苗的免疫原性,我们制备了携带A/Netherlands/219/03(H7N7)和A/Anhui/1/2013(H7N9)血凝素抗原的重组腺病毒载体疫苗Ad5-NL和Ad5-AH,同时用反向遗传学技术拯救出H7/NL/219/2003-PR8和H7N9/AH/1/13-PR8重组流感病毒并灭活制备成全灭活疫苗NL-PR8和AH-PR8,分别免疫小鼠后检测血清中血凝抑制活性和中和抗体效价以及对其他H7毒株的交叉保护反应。研究结果显示,相比较于全灭活病毒疫苗,腺病毒载体流感疫苗能诱导机体产生更高的血凝抑制抗体和中和抗体。AH-HA的免疫原性优于NL-HA,无论是重组腺病毒疫苗Ad5-AH还是全病毒灭活苗AH-PR8,诱导的体液免疫应答均高于Ad5-NL和NL-PR8;同时,重组腺病毒疫苗Ad5-AH的交叉反应性高于Ad5-NL。综上,本研究比较了新型H7N9流感病毒的免疫原性,探索了复制缺陷性腺病毒载体疫苗作为H7N9候选疫苗的可能性,为H7N9流感病毒疫苗的研究提供了新思路。
[Abstract]:H7N9 influenza virus was first infected in humans at the end of March 2013, and the body lacks specific protective antibody against H7N9. The vaccine is an effective method to prevent the transmission of H7N9 virus in the population.The results show that the immunogenicity of the inactivated influenza vaccine of H _ 7N _ 7 / A / A / N _ (19 / 03) subtype is low, and the immunogenicity can be achieved by increasing the amount of antigen, adding adjuvant, multiple immunization and so on.At present, the immunogenicity of H7N9 influenza virus is still unknown.The replication-deficient adenovirus vector has the advantages of fast, safe, strong humoral and cellular immune response.Some studies have shown that the recombinant adenovirus vector influenza vaccine carrying H5HA can produce higher neutralizing antibody titer and cross-protection activity than the inactivated vaccine.In this study, the immunogenicity of H7 recombinant adenovirus vaccine and whole virus inactivated vaccine was compared.We prepared recombinant adenovirus vector vaccine Ad5-NL and Ad5-AH carrying A / R / 219 / 03 H7N7) and A / Anhui / 1 / 2013 H7N9). We also used reverse genetics techniques to save H7/NL/219/2003-PR8 and H7N9/AH/1/13-PR8 recombinant influenza viruses and inactivate them to make NL-PR8 and AH-PR8 vaccine, respectively, and immunize mice with AH-PR8.The hemagglutination inhibitory activity, neutralizing antibody titer and cross protection against other H7 strains were detected.The results of the study showed that, compared with the total inactivated virus vaccine,The immunogenicity of AH-HA induced by adenovirus vector influenza vaccine was higher than that of NL-HA.The humoral immune response of recombinant adenovirus vaccine Ad5-AH or whole virus inactivated vaccine AH-PR8 was higher than that of Ad5-NL and NL-PR8.The cross reactivity of recombinant adenovirus vaccine Ad5-AH was higher than that of Ad5-NL.In summary, the immunogenicity of novel H7N9 influenza virus was compared, and the possibility of replication-deficient adenovirus vector vaccine as H7N9 candidate vaccine was explored, which provided a new idea for the study of H7N9 influenza virus vaccine.
【学位授予单位】：安徽大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R511.7

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