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Comparison And Analysis Of The Immune Effectiveness After Administration Of Live Attenuated And Inactivated Varicella Zoster Vaccine Delivered By Different Routes Respectively

Posted on:2014-01-24Degree:MasterType:Thesis
Country:ChinaCandidate:H P LiuFull Text:PDF
GTID:2234330395998154Subject:Biochemistry and Molecular Biology
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Varicella-zoster Virus is a double-strand DNA virus and belongs to herpes virusclass, α-herpes virus subclass. Primary infection cause chicken pox after which thevirus remains latent in nerve ganglia for a long time. In some conditions, the latentvirus can be reactivated thus leading to shingles. For varicella zoster, the Okavaricella zoster vaccine is widely used and it has contributed a lot to the reduce theoutbreak of varicella zoster since routinely vaccinated in1995. In spite of theattenuated nature of the varicella zoster vaccine, around6%healthy subjects developvaricella-like rash after first time administration. Moreover, live attenuated vaccine isnot applicable to the immunocompromised individuals, such as those suffering fromhematological malignancy, undergoing immunosuppressive therapies, receivedhematopoietic stem cell transplant or solid organ transplant, and the HIV-infectedpatients or with autoimmune disease. Comparing to healthy population, there is ahigher incidence for them to develop zoster. Furthermore, it is more likely for them todevelop severe and life-threatening complications. Therefore, there is an urge need todevelop a safe vaccine which can effectively protect the immunocompromisedindividuals from shingles and the complications. Specifically to theimmunocompromised, the researchers have investigated the efficiency ofnon-replicated vaccines in preventing the infection of the virus, such as the subunitvaccines, virus-like particle vaccines and the inactivated vaccines. Given their lost ofvirulence, it seems to be more safe and stable compared to those live vaccines. As forherpes zoster, heat inactivated vaccine has been utilized for clinical trials, however,given the lack of ability to replicate in vivo, the immune effectiveness still needs to be strengthened. Based on this, we consider whether other delivery route could carrypositive result on the immune effect.In regards to the delivery route of immunization, most vaccines are deliveredthrough the traditional subcutaneous or intramuscular route. However, due to somepotential advantage of the intradermal route, it had been gaining more and moreattention. Firstly, there are abundant professional antigen present cells and otherimmune cells, including dermal dendritic cells, microphages, mast cells, leukocyteand lymphatic and blood capillary vessels, thereby contributing to the immediateinteraction between different immune cells and subsequent activation of the innateimmunity as well as the adaptive immunity. Therefore, comparing to the muscular andthe hypodermis, it will induce more effective immune response after an intradermaldelivery and especially in low-responders. Nowadays, vaccines approved toadministrate through intradermal route are BCG and rabies vaccines. Meanwhile, atleast twelve vaccine have been under clinical trails delivered by intradermal route,including influenza vaccines, hepatitis A vaccine, hepatitis B vaccine, polio vaccine,measles vaccine, yellow fever vaccine, tetanus vaccine and so on.This experiment aims to compare the immune effect after administrating the samedose live and inactivated varicella zoster vaccine in Balb/c mice through theintradermal and subcutaneous delivery route. We mainly study level of the humuroland cellular immunity. In humurol immunity, the difference of the level of specificanti-VZV IgG in serum after different delivery route is investigated by FluorescentAntibody to Membrane Antigen assay. In cellular immunity, we utilize ELISPOT andLuminex to investigate the ability of splenocyte to secret IFN-γand Th1/Th2cytokines. By comparing and analyzing of the data, we furthermore make anevaluation about the immune effectiveness of live and inactivated varicella zostervaccine delivered by different routes. Generally, it provides reference for theapplicability of the varicella zoster vaccine and the choice of different delivery route.
Keywords/Search Tags:live attenuated varicella zoster vaccine, subcutaneous delivery, inactivated varicella zoster vaccine, Intradermal delivery
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