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Preliminary Study On Hepatitis A Vaccine - Induced Immunity

Posted on:2008-01-21Degree:MasterType:Thesis
Country:ChinaCandidate:Z N YangFull Text:PDF
GTID:2204360215463358Subject:Pathogen Biology
Abstract/Summary:PDF Full Text Request
Infection with HAV could be well prevented by hepatitis A vaccine. Inactivated hepatitis A vaccine has been used worldwide , and live attenuated hepatitis A vaccine has also been widely used in our country.Clinical trials and postmarket use showed that two kinds of hepatitis A vaccines had excellent immunogenicity, They were fully confirmed in seroconversion,GMT and long-lasting protection after immunization.However, it was incomprehensive to evaluate the immune protection by means of humoral immune response only, and to ignore the effect of cellular immune response. With the development of molecular immunology and basic medicine, people have begun to realize the significance of cellular immune response induced by vaccines.In this paper we focus the research on the cellular immune responses induced by the two kinds of vaccine, live attenuated hepatitis A vaccine and inactivated hepatitis A vaccine, which are generally immuned in our country. The goal of the research is to evaluate the systematic immunological effect of live attenuated and inactivated hepatitis A vaccines, to investigate whether the effects of cellular immune response induced by the two kinds of HAV vaccines were identical, and the extent of their differences, meanwhile the HAV antibody concentration and seroconversion were measured. So that we could evaluate the effect of cellular immunity at earlier phage of HAV infection.A total of 18 healthy volunteers(18~22 years old) were enrolled in this study,Fourteen volunteers with HAV antibodies negative were randomized into two trial groups to be injected Inactivated hepatitis A vaccine or attenuated hepatitis A vaccine respectively. Meanwhile, two volunteers who had been injected HAV vaccine two years ago were boosted as positive control and other two volunteers were set as negative control who would be injected one of the HAV vaccines afterward. All volunteers' heparinized venous blood were separately collected at O-(pre-vaccination), 1-, 2-, 3-, 4-, 5-, 6-, 24-, 25- week, then quality and quantity criteria were used to evaluate the the anti-HAV antibody, meanwhile the PBMC were collected . The level of IFN-γand IL-2 secreted by effect T-cell using ELISPOT, the percentage of lymphocytes secretingIFN-γamong CD3/CD4~+ T and CD3/CD8~+ T-cell using ICS technique, the concentrationof IFN-y,IL-2,IL-10,IL-4 in PBMC culture supernatants(grown in the presence or absence of HAV) by Luminex were determined after collected PBMC were stimulated by specific HAV antigen in vitro.The results indicated that methods used in the study such as ELISPOT,ICS,Lum-inex are of high sensitivity, specificity and are stable ,reliable, which can be applied to the assessment of the specific cellular immune after vaccination. Furthermore, Our data shows that live attenuated and inactivated hepatitis A vaccines elicits an earlier virus antigens specific cytotoxic lymphocytes and the high level of its effect element IFN-γwould been examined after primary immunization. Some differences about the virus specific T cellular immune responses induced by these two vaccines were observed at some week point, which may be attribute to the difference of the antigen amount existed in these two kinds of vaccines and duplicating and propagating of live vaccine in vivo. Our findings also suggest that evoked immune memory were existed among those who had already been injected with HAV vaccine after booster inoculation. They also had were existed rapidly increased, high concentration of antibody, anti-virus cytokine IFN-γ,and virus-specific T cell propagating, when restimulated by HAV antigen.In conclusion, Both live attenuated and inactivated HAV vaccines induced specific humoral and cellular immune responses,there were some differences about the virus specific T cellular immune responses induced by the two kinds of vaccines at some week point.This study set up primary methods to evaluate the cellular immunity against Hepatitis A vaccine. Moreover,We complementarited the evaluation documents of the immune effects of HAV vaccine through probing into and analysing the immune responses of human being administrated with HAV. By correlative study of cellular immunity against Hepatitis A vaccine, we filled up the vacancy of cellular immune effects of human being induced by domestic and imported HAV live attenuated vaccine. Also we supplied the refference evidence for comprehensively evaluaing the cellualr immune effects induced by HAV vaccine and provided foundations for post-exposure prophyaxis against HAV.
Keywords/Search Tags:Hepatitis A Vaccine, Humoral immune response, Cellular immune response, ELISPOT, ICS, Luminex, Cryopreservation
PDF Full Text Request
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