流感疫苗在成人及老人族群的免疫反應及效益評估

Evaluation the Efficacy and Immunity of Influenza Vaccination in Adult and Elderly People

陳建壬(Chien-Ren Chen)

指導教授 ： 陳志豪

中山醫學大學/醫學院/醫學研究所/碩士(2008年)

摘要

流感是重要的呼吸道疾病之ㄧ，每年世界各地都會出現流感之流行，而且臨床上常造成許多嚴重的合併症或死亡，在二十世紀曾發生三次的流感大流行，造成人類生命財產的重大損失，這幾十年來，雖然在抗流感病毒的藥物上有很大的進步，但接種流感疫苗仍是防治流感的最佳策略。本研究利用血球凝集抑制試驗評估於2006年末接種流感疫苗 (GlaxoSmithKline) 的成人及老人族群對抗2006-2007及2007-2008流感季本土流行株的血清抗體效價，另外也對這些病毒株的血球凝集素 (HA) 基因序列作演化分析，探討流感疫苗的效益以及病毒株間的演化關係。我們採集30名成人 (平均35.2±6.6歲) 及30名老人 (平均67.7±4.2歲) 接種疫苗前後間隔3週的配對血清，共120支檢體，和連續兩年的本土流感流行株抗原進行血球凝集抑制試驗，並分析其抗體幾何平均效價、血清轉化率、血清轉化係數及血清保護率。研究結果顯示兩個族群在接種疫苗後的抗體幾何平均效價有明顯的增加 (p < 0.05)。在血清轉化係數方面，2006-2007年除了成人族群在對A/Taiwan/0586/2006(H1N1) 的抗體反應較差外，其他都符合歐洲CPMP (Committee for Proprietary Medicinal Products) 的標準，但隔年就只有對A/Taiwan/80175/2008(H3N2) 的抗體反應符合標準。另外，在2006-2007年除了對B/Taiwan/0050/2006的抗體反應未符合歐洲CPMP血清轉化率的標準外，其他都達到標準，2007-2008年則只有對A/Taiwan/80175/2008(H3N2) 的反應達到標準。至於在血清保護率方面，2006-2007年兩個族群在接種疫苗後的血清保護率都達到70 %的閾值標準，然而隔年就只有老人族群接種疫苗後對A/Taiwan/80175/2008(H3N2) 的血清保護率達到標準。演化分析的結果則顯示在2007-2008的本土流行株中，以A/Taiwan/80175/2008 (H3N2) 與疫苗株的演化關係最為接近，而B/Taiwan/80141/2008與疫苗株屬不同的系代，演化差異最大。綜合我們的研究結果，建議每年應定期接種流感疫苗，它可以有效的誘發成人及老人族群的血清抗體反應，尤其若是疫苗株與流行株的抗原性高度吻合，流感疫苗將會有更高的效益。

關鍵字

幾何平均效價 ； 血清保護率 ； 血球凝集抑制試驗 ； 演化分析

並列摘要

Influenza is one of the important respiratory diseases that infects globally and possibly causes significant morbidity and mortality in human beings. Three influenza pandemics took place during the 20th century. Despite of the improvement in the antiviral therapies during the past decades, vaccination is still the most effective method of prophylaxis. In this study, we used hemagglutination inhibition (HAI) test to assess antibody responses against current influenza viruses in 2006-2007 and 2007-2008 between the adults and the elderly who were vaccinated with influenza vaccine (GlaxoSmithKline) at the end of 2006. Besides, the phylogenetic analysis of the hemagglutinin (HA) gene among these current strains was also performed. We would like to know the efficacy of the influenza vaccine and the evolutionary relationship among these virus strains. Totally 120 serum samples (including pre-vaccination and post-vaccination paired sera collected at an interval of three weeks) were collected from 30 adults (mean age: 35.2±6.6years old) and 30 geriatric volunteers (mean age: 67.7±4.2years old) . Then, HAI test was performed against local circulating strains during two consecutive influenza seasons. The antibody titers of both groups were analyzed by geometry mean titers (GMTs), seroconversion rates, seroconversion factors and seroprotection rates. The results revealed that the GMTs of both groups were significantly increased after vaccination (p<0.05). The seroconversion factors indicated that the antibody response of both groups fitted the criteria of guidelines of the European CPMP (Committee for Proprietary Medicinal Products), except that against A/Taiwan/0586/2006(H1N1) in adults in 2006-2007. However, only the antibody response against A/Taiwan/80175/2008(H3N2) fitted the criteria in 2007-2008. The seroconversion rates of elderly were greater than 30% while the rates of adults were greater than 40%, except that against the B/Taiwan/0050/2006 in 2006-2007. Similarly, only the antibody response against A/Taiwan/80175/2008(H3N2) fitted the criteria in 2007-2008. Besides, the seroprotection rates reached the threshold of 70% for all virus strains in both groups after vaccination in 2006-2007 while the rates were all below the threshold of the criteria next year, except that against A/Taiwan/80175/2008(H3N2) in elderly.The phylogenetic analysis also showed the A/Taiwan/80175/2008(H3N2) was located most nearby the vaccine strain while the B/Taiwan/80141/2008 was located in an independent lineage and distinct from the vaccine strain. In conclusion, our results suggested that the annual influenza vaccination program is appropriate and could provide a protective immunity in the adult and the elderly. In addition, there is a higher efficacy if a good match between vaccine and circulating virus strains.

並列關鍵字

geometry mean titers ； seroprotection rates ； hemagglutination inhibition test ； phylogenetic analysis

參考文獻

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