mRNA疫苗能否改變對抗伊波拉的鬥爭?
繼成功的 COVID-19 mRNA 疫苗之後,該技術有望在預防另一種致命病原體方面發揮作用。
資料來源:Max Kozlov / 新聞 / 2022 年 11 月 7 日 / 自然 / 財團法人台灣紅絲帶基金會編譯
沒有疫苗被證明可以預防目前在烏干達流行的伊波拉病毒類型。圖片來源: Luke Dray/Getty
依賴 mRNA 技術的 COVID-19 疫苗被認為改變了人類對抗冠狀病毒大流行的鬥爭。這些疫苗——一種由製藥巨頭輝瑞公司與德國生物技術公司 BioNTech 製造,另一種由美國製藥公司 Moderna 製造——在短短幾個月內加速通過臨床試驗,並在開發開始不到一年後獲得主要監管機構的批准。現在,當烏干達在沒有經過驗證的疫苗的情況下與一種伊波拉病毒作鬥爭時,是否有針對這種致命病毒的 mRNA 疫苗?這種疫苗是否會同樣改變對抗伊波病毒的鬥爭?
有兩種疫苗已被證明可以預防伊波拉病毒:rVSV-ZEBOV (Ervebo),由新澤西州拉威的默克公司銷售,以及 Ad26.ZEBOV/MVA-BN-Filo (Zabdeno/Mvabea),由總部位於新澤西州新布倫瑞克的強生公司銷售,。但這些疫苗被認為只能預防一種病毒:薩伊株伊波拉病毒,該病毒在 2013 年至 2016 年期間在西非引起了大規模流行。目前尚無針對蘇丹株伊波拉病毒的有效疫苗,該病毒株是烏干達當前爆發的罪魁禍首,迄今為止,已造成 132 人感染和 51 人死亡。
「非洲的公共衛生將從更多選擇中受益」,位於蒙大拿州漢密爾頓的美國國家過敏和傳染病研究所病毒學實驗室負責人海因茨·費爾德曼說,他的研究為現有伊波拉疫苗的開發做出了貢獻。
多重保護
美國德克薩斯州立大學加爾維斯頓醫療分部的病毒學家 Alex Bukreyev 說,最好有一種疫苗可以對多種絲狀病毒(包括伊波拉病毒和其他引起出血性疾病的病原體,如馬堡病毒)提供保護,而不是擁有許多單獨的疫苗。這將使疫苗在貧困和農村地區的配送變得更加容易,因為每次爆發不同的伊波拉病毒株時都不需要進行昂貴的新疫苗接種活動。
目前的兩種薩伊株伊波拉病毒疫苗都依賴使用於另一種活性病毒的技術,這限制了某些人可以接受它們。在大多數情況下,Ervebo 僅被批准用於 18 歲以上的人群——其副作用可能令人不快。 Bukreyev 說,強生公司的方案可以提供給一歲及以上的人,但必須分兩劑給藥,相隔八週,這在快速增長的疫情中並不理想。
費城賓夕法尼亞大學專門研究 mRNA 技術的疫苗學家 Norbert Pardi 說,mRNA 疫苗可以解決其中的一些挑戰。與許多其他遞送平台不同,mRNA 疫苗不含病毒。相反,他們使用信使 RNA 來編碼在病毒表面發現的關鍵蛋白質。當 mRNA 進入人體細胞時,細胞開始製造蛋白質,從而引發針對病毒的免疫反應。
如果出現新物種,很容易調整 mRNA 編碼的蛋白質,或者包含不同的 mRNA 鏈以同時誘導針對多種絲狀病毒的保護。 Pardi 說,在預防 COVID-19 方面,mRNA 疫苗還具有安全性和有效性的「真實證據」:它們已被用於超過 50 億人。
但費爾德曼指出,COVID-19 和伊波拉病毒是截然不同的疾病。 COVID-19 疫苗在預防嚴重感染和死亡方面最有效,而不是預防感染。這種限制部分是由於逃避免疫的變異株出現的速度有多快。他說,任何伊波拉疫苗都有助於預防感染——以及阻止嚴重疾病——以避免繼續傳播並迅速遏制致命病原體,這一點至關重要。
Pardi 說,伊波拉病毒的變異速度幾乎沒有冠狀病毒那麼快,因此免疫逃避變體的不斷進化並不令人擔憂。但目前尚不清楚單次 mRNA 注射能否提供強有力的保護,防止伊波拉病毒感染,Feldmann 說。而且,與目前的薩伊株伊波拉病毒疫苗一樣,mRNA 疫苗必須在低溫條件下儲存,這會使配送複雜化。
疫苗交易已接近了
答案可能很快就會出現,但可能還不足以幫助烏干達持續爆發的伊波拉病毒。據彭博社報導,總部位於麻薩諸塞州劍橋市的 Moderna 即將達成協議,開發一種針對伊波拉病毒和其他絲狀病毒的 mRNA 疫苗。但目前尚不清楚 Moderna 希望針對哪個病毒株——或者它是否想開發一種針對多種病毒株的疫苗。
有一些研究顯示,mRNA 方法可能有助於應對伊波拉病毒。 2017 年,Bukreyev 和他的同事發現 兩種 mRNA 疫苗製劑在豚鼠身上產生了免疫反應。十隻接種動物在感染豚鼠適應的伊波拉病毒後均未死亡,而所有五隻對照動物在十天內均因重病而死亡或死亡。
與 Moderna 合作進行這項研究的 Bukreyev 表示,如果交易成功,可能需要在非人類靈長類動物身上進行大約三年的研究,才能確定疫苗是否對動物有效,然後則需要進行人體臨床試驗。
Pardi 希望 Moderna 和其他公司嘗試 mRNA 方法,並尋求針對多種病毒株的保護。「我們並不知道哪種伊波拉病毒株會導致下一次伊波拉病毒疫情的爆發」,他說。
doi:https://doi.org/10.1038/d41586-022-03590-y
參考文獻:Meyer, M. et al.《感染症期刊》。 217, 451–455 (2018)。
Can mRNA vaccines transform the fight against Ebola?
On the heels of successful COVID-19 mRNA vaccines, the technology could hold promise in protecting against another deadly pathogen.
Max Kozlov / NEWS / 07 November 2022 / Nature
There are no vaccines proved to protect against the type of Ebola currently circulating in Uganda.Credit: Luke Dray/Getty
COVID-19 vaccines that rely on mRNA technology are credited with transforming humanity’s fight against the coronavirus pandemic. The vaccines — one made by drug giant Pfizer with German biotech firm BioNTech, another by US pharmaceutical company Moderna — sped through clinical trials in just months and gained approval from major regulatory bodies less than a year after development began. Now, as Uganda battles a type of Ebola without proven vaccines, is an mRNA vaccine against the deadly virus on the cards? And would such a vaccine similarly transform the fight against Ebola?
There are two vaccines that are already proven to protect against Ebola: rVSV-ZEBOV (Ervebo), sold by Merck of Rahway, New Jersey, and Ad26.ZEBOV/MVA-BN-Filo (Zabdeno/Mvabea), sold by Johnson & Johnson, which is based in New Brunswick, New Jersey. But the vaccines are thought to protect against only one species of the virus: Zaire ebolavirus, which caused a large epidemic in West Africa between 2013 and 2016. There are no proven vaccines against Sudan ebolavirus, the species responsible for the current outbreak in Uganda, which has so far caused 132 infections and 51 deaths.
“Public health in Africa would benefit from further options,” says Heinz Feldmann, head of the US National Institute of Allergy and Infectious Diseases’ Laboratory of Virology in Hamilton, Montana, whose research contributed to the development of the existing Ebola vaccines.
Multiple protection
It would be ideal to have a vaccine that confers protection against multiple filoviruses — the family that includes Ebola virus and other pathogens that cause haemorrhagic diseases, such as Marburg virus — rather than having many separate vaccines, says Alex Bukreyev, a virologist at the University of Texas Medical Branch at Galveston. This would make vaccine distribution easier in poor and rural areas, because costly new vaccination campaigns wouldn’t be needed with every outbreak of a different Ebola species.
Both current Zaire ebolavirus vaccines use technology that relies on another active virus, which limits who can receive them. In most circumstances, Ervebo is approved for use only in people over 18 — and its side effects can be unpleasant. Johnson & Johnson’s regimen can be offered to people one year old and up, but it must be given in two doses, eight weeks apart, which is not ideal in a rapidly growing outbreak, Bukreyev says.
mRNA vaccines could remedy some of these challenges, says Norbert Pardi, a vaccinologist at the University of Pennsylvania in Philadelphia who specializes in mRNA technology. Unlike many other delivery platforms, mRNA vaccines don’t contain a virus. Rather, they use messenger RNA to encode key proteins that are found on the surface of a virus. When the mRNA enters a person’s cells, the cells start to make the protein, which triggers an immune response against the virus.
It’s easy to tweak the proteins that the mRNA encodes if a new species emerges, or to include different strands of mRNA to induce protection against multiple filoviruses at once. mRNA vaccines also have the benefit of “real-life evidence” of their safety and effectiveness when it comes to protecting against COVID-19: they have been administered to more than five billion people, Pardi says.
But COVID-19 and Ebola are very different diseases, Feldmann notes. The COVID-19 vaccines have been most effective in warding off severe infection and death, rather than preventing infection. This limitation is caused in part by how quickly immunity-evading variants have cropped up. It’s crucial that any Ebola vaccines help to prevent infection — as well as stopping severe disease — to avoid onward transmission and contain the lethal pathogen quickly, he says.
Ebola viruses don’t mutate nearly as fast as coronaviruses, so constant evolution of immune-evading variants is less of a concern, Pardi says. But it’s not clear whether a single mRNA shot can provide robust protection against infection with Ebola, says Feldmann. And, like the current Zaire ebolavirus vaccines, mRNA vaccines must be stored in cold conditions, which can complicate distribution.
Vaccine deal close
Answers might be coming soon, but probably not soon enough to help with the ongoing Ebola outbreak in Uganda. Moderna, which is based in Cambridge, Massachusetts, is close to securing a deal to develop an mRNA vaccine against Ebola and other filoviruses, according to news agency Bloomberg. But it’s unclear which species Moderna hopes to target — or whether it wants to develop one vaccine against multiple species.
There is some research suggesting that the mRNA approach might work to tackle Ebola. In 2017, Bukreyev and his colleagues found that two mRNA vaccine formulations produced immune responses in guinea pigs. None of the ten inoculated animals died after they were infected with a guinea pig-adapted ebolavirus, whereas all five control animals died or were killed because of severe sickness within ten days.
Bukreyev, who worked with Moderna on the study, says that if the deal goes through, it will probably take about three years of research in non-human primates to find out whether the vaccine is effective in the animals, and then human clinical trials will be needed.
Pardi hopes that Moderna and other firms will try the mRNA approach, and seek protection against multiple species. “We don’t know which Ebola virus will cause the next Ebola outbreak,” he says.
doi: https://doi.org/10.1038/d41586-022-03590-y
References
1.Meyer, M. et al. J. Infect. Dis. 217, 451–455 (2018).