愛滋病毒感染者施打七價結合型肺炎鏈球菌疫苗血清反應之一年追蹤

One-year Longitudinal Follow-up of Serologic Responses to Vaccination with 7-Valent Pneumococcal Conjugate Vaccine among HIV-infected Adult Patients

路景蘭(Ching-Lan Lu)

指導教授 ： 張上淳

共同指導教授 ： 張淑媛(Sui-Yuan Chang)

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.00221

摘要

愛滋病毒感染者較沒有感染愛滋病毒的一般人容易發生侵入性肺炎鏈球菌疾病。在沒有高效能的抗病毒藥物組合治療(俗稱雞尾酒療法)的年代，愛滋病毒感染者感染侵入性肺炎鏈球菌疾病的風險為一般民眾的100倍；然而，愛滋病毒感染者在接受高效能的抗病毒藥物治療後，感染侵入性肺炎鏈球菌疾病的風險仍為一般民眾的35到60倍。有鑑於此，美國疫苗接種諮詢委員會建議愛滋病毒感染者施打23價肺炎鏈球菌疫苗。雖然多數文獻支持23價肺炎鏈球菌多醣體疫苗可增加愛滋病毒感染者保護力，但仍有文獻指出23價肺炎鏈球菌多醣體疫苗所引起的抗體效價受到多重因子影響，例如：在未同時接受雞尾酒治療病患或是CD4細胞數量較低的愛滋病毒感染者，接種23價肺炎鏈球菌多醣體疫苗後產生抗體反應會比較差。此外，在一般病患接種23價肺炎鏈球菌多醣體疫苗後，血液中可以維持足夠保護性的抗體濃度的時間大約是五年，但是在愛滋病毒感染病患，這個期間可能不到三年。西元2000年美國食品藥物管制局通過7價蛋白結合型肺炎鏈球菌疫苗上市，適用於2歲以下幼童和2-9歲的高危險群，共需接種四劑。國外研究發現愛滋病毒感染者施打7價蛋白結合型肺炎鏈球菌疫苗後，其抗體效價比接種23價肺炎鏈球菌多醣體疫苗的病患來得高。但是目前仍不清楚成人該施打多少劑的7價蛋白結合型肺炎鏈球菌疫苗。
　　本研究將愛滋病毒感染者分為兩個組群，一組80人接種兩劑7價蛋白結合型肺炎鏈球菌疫苗，兩劑間隔一個月;另一組79人只接種一劑疫苗，接種後每三個月追蹤血請抗體濃度，共追蹤一年。血清抗體濃度是以ELISA方法偵測受試者血清中對血清型6B、14、19F、和23F四種肺炎鏈球菌血清型的抗體濃度。本研究的第一個目標為分析比較兩組疫苗接種者血清抗體上升兩倍以上的比例是否有所不同，第二個目標則是評估影響抗體產生的相關因子；另外，我們也評估7價蛋白結合型肺炎鏈球菌疫苗對愛滋病毒感染者短期內CD4細胞數目和病毒量的影響。
　　我們的追蹤研究結果發現，愛滋病毒感染者在接種疫苗後第十二個月，兩劑組中有85%的受試者對至少一種肺炎鏈球菌血清型產生反應，57.5%對至少兩種肺炎鏈球菌血清型產生反應，28.8%對至少三種肺炎鏈球菌血清型產生反應，13.8%對四種肺炎鏈球菌血清型都產生反應；一劑組中則有72.2%對至少一種肺炎鏈球菌血清型產生反應，44.3%對至少兩種肺炎鏈球菌血清型產生反應，27.8%對至少三種肺炎鏈球菌血清型產生反應，6.3%對四種肺炎鏈球菌血清型都產生反應。在不同血清型方面，施打7價蛋白結合型肺炎鏈球菌疫苗後第六個月，血清型14的反應率最高（兩劑組：66.2%；一劑組：64.6%），再來是血清型23F（兩劑組：66.2%；一劑組：59.5%），血清型19F（兩劑組：46.8%；一劑組：35.4%），而血清型6B最差（兩劑組：42.9%；一劑組：31.7%）。在第十二個月，血清型14的反應率在兩劑組為57.0%，一劑組為57.0%，血清型23F在兩劑組為60.0%，一劑組為45.6%，血清型19F在兩劑組為33.8%；一劑組為26.6%，血清型6B在兩劑組為32.5%；一劑組為21.5%。在施打一劑或兩劑疫苗後第三個月比較容易對四種肺炎鏈球菌血清型都發生反應，打兩劑疫苗者在第六個月比較容易對四種肺炎鏈球菌血清型都發生反應。另外，最低點CD4細胞數目越高者、異性戀者、和B型肝炎帶原者也比較容易對四種肺炎鏈球菌血清型都發生反應。在施打疫苗後第三個月受試者在血清型6B、14、和19F都可以觀察到基礎血清抗體量越高的病患，之後越不容易達到兩倍以上的增加；之前感染過B型肝炎的受試者，也較不容易發生反應；在接受兩劑疫苗的受試者，第三個月的血清型6B抗體反應和第六個月的血清型19F抗體反應比較好，除此之外並沒有差別。
總結，愛滋病毒感染者在接種7價蛋白結合型肺炎鏈球菌疫苗後一年，根據肺炎鏈球菌血清型的不同，反應率介於21.5%至60.0%間。接種兩劑7價蛋白結合型肺炎鏈球菌疫苗的愛滋病毒感染者，抗體的持久度並不會比僅接受一劑者來得好。

關鍵字

愛滋病毒感染 ； 肺炎鏈球菌 ； 肺炎鏈球菌疫苗 ； 7價蛋白結合型肺炎鏈球菌疫苗 ； 血清抗體反應

並列摘要

Clinical studies have shown that vaccination with pneumococcal conjugate vaccine (PCV) decreases incidence of invasive pneumococcal diseases among HIV-infected children and adults. However, longitudinal follow-up of serologic responses to conjugated pneumococcal vaccination are rarely performed among HIV-infected adult patients receiving combination antiretroviral therapy (CART).
　　　From October 2008 to April 2009, 159 HIV-infected adult patients were enrolled who had never received pneumococcal vaccine before, were not taking immunosuppressives, or had no active opportunistic illnesses. Eighty patients received two doses of 7-valent PCV given one month apart and 79 received one dose. Anticapsular antibody responses against 4 serotypes were examined (6B, 14, 19F, and 23F) at the 3rd, 6th, 9th, and 12th month following vaccination with the use of ELISA after absorption with 10 μg/ml cell-wall polysaccharide and 30 μg/ml 22F polysaccharide. Significant antibody responses were defined as 2-fold or greater increase of antibody level following vaccination compared to baseline.
　　　Antibody response rates following vaccination varied with the 4 serotypes examined during follow-up. At 6th month, the rate was highest for serotype 23F (1-dose vs. 2-dose, 60.0% vs. 61.8%, P=0.75), followed by 14 (58.2% vs. 63.6%, P=0.47), 19F (36.4% vs. 49.1%, P=0.15), and 6B (34.5% vs. 40.0%, P=0.50). At 12th month, the 1-dose vs. 2-dose response rate for serotype 23F. 14, 19F, and 6B was 45.5% vs. 56.4% (P=0.25), 52.7% vs. 52.7% (P=0.99), 29.1 vs. 40.0 (P=0.23), and 23.6% vs. 30.9% (P=0.39), respectively. No significant differences of serotype-specific IgG concentrations for each serotype at the 4 time points were observed between patients receiving 1 dose and those receiving 2 doses of PCV except for serotype 6B at third month. Higher nadir CD4 count, heterosexual patients, and hepatitis B carrier were more likely to mount antibody responses to all 4 pneumococcal serotypes tested. Patients who received 2 doses of vaccine had a higher response rate at sixth month compared to patients who received 1 dose.
In this longitudinal follow-up study of 7-valent conjugated pneumococcal vaccination, the response rate to different serotypes one year after PCV vaccination ranged from 21.5% to 60.0% among HIV-infected patients. Patients who received 2 doses of PCV achieved similar serological responses against 4 serotypes to those who received 1 dose of PCV.

並列關鍵字

human immunodeficiency virus ； Streptococcus pneumoniae ； invasive pneumococcal disease ； pneumococcal vaccine ； 7-valent pneumococcal conjugate vaccine

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