編按:英國科學家於本月五日宣布 HIV 感染者「倫敦病人」在接受造血幹細胞移植後,血液中 HIV 病毒感染跡象完全消失,為全球第二例功能性治癒愛滋病患者。而後在六日,荷蘭科學家也在西雅圖愛滋病毒會議(CROI)宣布第三位在停藥後3個月也未在體內發現 HIV病毒的「杜塞道夫病人」( Düsseldorf patient)。他們是接受了怎樣的治療?愛滋病能夠痊癒已經是現在進行式了嗎?
早在 1996 年就有研究者發現,CCR5基因編碼的蛋白是 HIV 病毒入侵人體的「順風車」。CCR5 蛋白位於 CD4+ 輔助性 T 細胞的表面,像一個「小抓子」, HIV 病毒會利用它入侵輔助性 T 細胞,進而破壞整個免疫系統。更重要的是,研究人員發現一小部分人的兩個 CCR5 基因拷貝都產生了 CCR5 Δ32突變,也就是說缺失了 32 個核苷酸,這讓他們表達的 CCR5 蛋白比正常情況下要短,不能到達 T 細胞表面,因此他們的 T 細胞對 HIV 感染有高度抵抗力。大約 1% 的高加索人遺傳了這樣的一對基因,但是在亞洲人、非洲人、美洲土著人中,這種基因非常罕見。
這次移植到「倫敦病人」體內的造血幹細胞就攜帶兩個CCR5 Δ32突變拷貝,保護輔助性 T 細胞免於 HIV 病毒感染。對於整個免疫系統來說,CD4+ 輔助性 T 細胞一旦能夠正常行使生理功能,就可以募集足夠的殺手 T 細胞,清除 HIV 病毒。
從上世紀九十年代起,多個研究組就將注意力放在了保護輔助性 T 細胞等免疫細胞不被 HIV 侵染的環節上,但直到二十一世紀臨床試驗的結果仍不理想。這時,「柏林病人」出現了。
史上第一例因骨髓移植「治癒」HIV的柏林病人
居住在德國柏林的 Timothy Ray Brown 1995 年被確診為 HIV 感染者,隨後一直服用抗逆轉錄病毒藥物控制病情,效果還算不錯。但是,2006 年他又患上了一種與 HIV 感染不相干的疾病——急性骨髓性白血病(acute myeloid leukemia)。Timothy 接受了化療,但白血病再次復發,為了活下去,他只能選擇利用他人的骨髓幹細胞在自己體內重建一個免疫系統。
兩次骨髓移植後,Timothy 的白血病被治好了,同時,他在手術結束後再也沒有服用抗逆轉錄病毒藥物。從 2007 年手術結束到現在,醫生在他的血液、肝臟、腸道、大腦、淋巴組織及血漿中都沒有檢測到 HIV 病毒。Timothy 自此成為世界首個感染 HIV 後被「治癒」的患者,為了保護他的隱私,學界給了他一個「柏林病人」的代號,Timothy 在 2010 年主動公開了自己的名字,希望能鼓勵 HIV 感染者。
目前,沒人知道「柏林病人」是不是被「徹底根治」(sterilizing cured)了,因為 HIV 可以把自己的基因插入各種細胞的染色體中,但我們無法檢測,先前也有過病毒從血液中消失後又捲土重來的病例。至於這位「倫敦病人」,目前醫生只能確定他血液中的 HIV 病毒消失了,但其餘組織的情況 2 年後才能確定。
對於大多數 HIV 感染者來說,只要服用抗 HIV 藥物,就可以維持一種與普通人接近的生活(藥物的副作用和壽命的縮短仍然是無法回避的問題)。像柏林病人和倫敦病人那樣接受骨髓移植,並終身服用抗免疫排斥藥物,仍然是個風險極高的選擇。
成功案例能否再複製?
那麼,相同的治療方法是否有希望應用於中國的 HIV 感染者?
首先,CCR5 突變不能阻止所有 HIV 病毒。雖然 CCR5 蛋白是 HIV 入侵細胞的鑰匙,但它並不是唯一的那一把。HIV 存在的不同種類的病毒株,各有各的偏好:
看時間:數據是2022年6~8月的數據,已能獲得充沛疫苗資源的國家來說該國國民絕大多數都有接種疫苗,以澳洲公布的數據來看16歲以上的澳洲人98%有接種一劑疫苗,兩劑為96.3%,三劑為71.7%,而New South Wales的人口數根據Population Australia這個網站上顯示在2022年6月底可能會達到 826萬人,而該地區16歲以上居民97%有接種一劑疫苗,兩劑為95.4%,三劑為69.6%(數據來源)
2. 分母要選對:在做如該信提到的感染機率比較時,我們必須要有施打疫苗者跟有施打疫苗者比,沒施打疫苗者跟沒施打疫苗者比,為什麼?因為你要比的是施打疫苗者跟沒施打疫苗者各自的感染機率,而以澳洲數據來看16歲以上施打至少一劑疫苗者有98%(20,209,451人),換而言之沒施打疫苗者大約是2%(412,428人);而在New South Wales16歲以上施打至少一劑疫苗者有97%(約8,017,050人),未施打疫苗者大約3%(大約247,950人)如果沒選對分母,算出來的數據會大錯特錯。
中和性抗體需要不短的成熟期,不可能在疫苗接種後幾週內產生[49][50],除非你已經是接種超過一劑疫苗,接著在第二或是第三劑疫苗施打後幾週內產生中和性抗體那可能還說得過去。而 mRNA 疫苗可以有效刺激與誘導 T 細胞與 B 細胞已在過往實驗中獲得證實[51],對於其導致心肌炎、心包炎與過敏等的可能機制也有不少研究團隊分析討論[52][53],並針對其安全性與哪些族群可能施打有較高的風險有所研究[52–54]。
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這篇真的很長,拉到最下方的作者貢獻(Author contributions)區可以看到這段話:S.S., G.N and A.K. all contributed substantially to the writing of the original draft. P.M. participated in the process of editorial revisions. 意思是作者序上的前三位作者負責寫這篇文章的草稿,而最後一位作者是通訊作者並且負責整篇文章的投稿與問題回覆。
而更有趣的是該篇發表的主要編輯為 Dr. Jose Luis Domingo,他主要研究方向為環境與食品污染對人類健康的影響,但他的研究其實不少備受批評外,他曾經在 Food and Chemical Toxicology 期刊上徵稿[6],希望有人能夠投稿關於 Covid-19 疫苗對人體有害的稿件,之後便有了這篇號稱「MIT 研究」的發表,但國外也早已有文章批評其是披著科學文獻皮的虛假訊息[7]。
講完該發表作者群與編輯的背景與事蹟後,讓我們看一看這篇文章發表在哪個期刊:Food and Chemical Toxicology 食品與化學毒理學期刊;而正統疫苗相關發表會去什麼期刊:生物學、免疫學等相關期刊。每個期刊代表的研究領域不同外,同時也代表該期刊的評審背景,你不可能在食品相關期刊找到免疫學專業的評審,反之亦然。倘若這篇疫苗有害論的發表整體論點清晰佐證明確,那早就應該可以上免疫學相關期刊,不用跑去食品期刊湊熱鬧。