前景廣闊的結核病疫苗獲得 5.5 億美元的強心劑
該候選藥物正在進入期待已久的 III 期試驗——如果成功，這將是 100 多年來針對該疾病的第一個新疫苗。
資料來源：Lilly Tozer / 2023 年 6 月 28 日 / 新聞 / Nature
結核病患者的 3D 電腦斷層掃描胸部掃描。圖片來源：Vsevolod Zviryk/Science Photo Library
在兩大資助者決定向其最後階段的臨床試驗投入 5.5 億美元後，一種有前途的結核病候選疫苗正在獲得新的生命。 如果成功，這將是一個多世紀以來市場上第一種新的結核病疫苗。
將參與試驗的南非結核病疫苗倡議副主任托馬斯·斯克里巴 (Thomas Scriba) 表示：「長期以來，結核病一直處於資源不足、資金不足和低估的狀態Ｊ」。
比爾及梅琳達·蓋茨基金會和 Wellcome 於 6 月 28 日宣布提供資金。 該候選疫苗由葛蘭素史克製藥公司開發，並已將其授權給蓋茨醫學研究所。
結核病由結核分枝桿菌引起，是世界上最大的流行病之一，每年奪去 160 萬人的生命。 低收入和中等收入國家的負擔尤其沉重。 這種差異在 COVID-19 大流行期間得到了戲劇性的體現，當時衛生服務中斷導致感染增加。
對抗結核病的一個主要挑戰是，細菌可以在體內隱藏多年，然後才成為出現症狀的活躍感染。 據估計，全球四分之一的人攜帶這種潛伏感染。 儘管 BCG 疫苗（卡介苗的縮寫）——於 1921 年開發出來，至今仍然是唯一可用的結核病疫苗——可以有效地保護兒童，但它對成人的幫助有限。
候選疫苗名為 M72/AS01E，旨在解決潛在感染。 2019 年發布的 II 期試驗數據顯示，它對攜帶該細菌的成年人有 54% 的療效。 但由於缺乏商業潛力，葛蘭素史克放棄了它。
Scriba 表示，早就該進入 III 期試驗了。 「在這一領域進行大量投資是完全合適的，這樣我們才能真正適當地應對結核病問題的嚴重性」，他補充道。 該試驗將在亞洲和非洲多個國家招募 26,000 名參與者。
M72/AS01E 由一種名為 M72 的融合蛋白（由兩種結核分枝桿菌抗原組成）和一種佐劑 AS01E 組成。 研究人員選擇抗原的依據是它們的高免疫原性，即激發免疫系統的強大能力，從而刺激對抗細菌所需的關鍵 T 細胞反應，並為未來的攻擊創造記憶細胞。
儘管活動性結核病可以通過六到九個月的藥物療程來治療，但漫長的過程導致了高的治療不完全率和抗生素耐藥性。 貧困人口無法獲得治療也仍然是一個障礙。
威康公司傳染病主管亞歷山大·皮姆 (Alexander Pym) 表示，對候選疫苗的投資是對預防結核病方面需要解決的差距的承認。 他補充道，新疫苗將改變遊戲規則。
正在進行第三階段試驗的其他一些候選結核疫苗也帶來了希望，即一種新的預防方法很快就會惠及人們。 但倫敦帝國理工學院結核病研究室主任 Ajit Lalvani 表示，M72/AS01E 迄今為止在數據數量和質量上都超過了其他數據庫。
「我相信，到本十年期末時，我們將有一種新的結核病疫苗上架，而且希望不止一種」，斯克里巴說。
doi：https://doi.org/10.1038/d41586-023-02171-x
Promising tuberculosis vaccine gets US$550-million shot in the arm
The candidate is moving to long-awaited phase III trials — if successful, it would be the first new jab against the disease in more than 100 years.
Lilly Tozer / 28 June 2023 / NEWS / Nature
A 3D computed tomography chest scan of a patient with tuberculosis.Credit: Vsevolod Zviryk/Science Photo Library
A promising vaccine candidate for tuberculosis is getting a new lease of life after two major funders have decided to pour US$550 million into its final phase of clinical trials. If successful, it would be the first new tuberculosis vaccine on the market in more than a century.
“TB has been chronically under-resourced, underfunded and underappreciated for a very long time,” says Thomas Scriba, the deputy director of the South African Tuberculosis Vaccine Initiative, who will be involved in the trials.
The Bill & Melinda Gates Foundation and Wellcome announced the funding on 28 June. The vaccine candidate was developed by drug firm GSK, which has licensed it to the Gates Medical Research Institute.
Tuberculosis, caused by Mycobacterium tuberculosis, is one of the world’s biggest epidemics, claiming 1.6 million lives each year. The burden is particularly high in low- and middle-income countries. This disparity was dramatically showcased during the COVID-19 pandemic, when disruptions to health services led to increased infections.
A major challenge in fighting tuberculosis is that the bacterium can hide in the body for years before becoming an active infection that shows symptoms. Estimates suggest that one in four people globally carry this latent infection. And although the BCG vaccine (short for Bacillus Calmette–Guérin) — which was developed in 1921 and remains the only available jab against tuberculosis — protects children effectively, it offers limited help in adults.
The vaccine candidate, called M72/AS01E, aims to tackle the latent infections. And it showed promise in data published from phase II trials in 2019, demonstrating a 54% efficacy in adults who hosted the bacterium. But GSK abandoned it owing to a lack of commercial potential.
Moving to phase III trials is long overdue, says Scriba. “It’s entirely appropriate that there’s substantial investment in this field so that we can actually appropriately respond to the magnitude of the TB problem,” he adds. The trial will recruit 26,000 participants in several countries across Asia and Africa.
M72/AS01E consists of a fused protein called M72 — comprised of two M. tuberculosis antigens — and an adjuvant, AS01E. Researchers chose the antigens on the basis of their high immunogenicity — a strong ability to provoke the immune system, which stimulates the crucial T-cell response needed to fight the bacteria and to create memory cells for future attacks.
Although active tuberculosis is treatable with a six-to-nine-month course of antibodies, the lengthy process has led to high incompletion rates and antibiotic resistance. The lack of access to treatment for those in poverty also remains a barrier.
The investment in the vaccine candidate is an acknowledgement of the gap that needs to be addressed in preventing tuberculosis, says Alexander Pym, Wellcome’s director of Infectious Disease. A new vaccine would be a game changer, he adds.
And a handful of other tuberculosis vaccine candidates in phase III trials offer hope that a new method of prevention will reach people soon. But M72/AS01E so far surpasses the rest in the quantity and quality of data, says Ajit Lalvani, the director of the Tuberculosis Research Unit at Imperial College London.
“I’m confident that by the end of this decade, we will have a new TB vaccine on the shelves, and hopefully more than one,” says Scriba.
doi: https://doi.org/10.1038/d41586-023-02171-x