即使在 COVID 之後，世界疫苗策略也在失敗
塞思伯克利 / 世界觀 / 2022 年 12 月 13 日 / 自然
如果沒有全球性的、公共資助的策略，市場將無法提供疫苗以在流行病激增之前阻止它。
四個星期前，我參觀了位於坎帕拉的穆拉戈國家轉診醫院，我曾在那裡工作。 今天，它是烏干達伊波拉隔離區之一的所在地。 在我訪問期間，我目睹了政府和醫護人員在沒有最有效的工具：疫苗的情況下為遏制這場可怕的疫情而面臨的一些挑戰。 蘇丹伊波拉病毒株已造成 56 人死亡，並蔓延至烏干達的 9 個地區，包括擁有 200 萬人口的首都和與其他國家接壤的地區。 如果它蔓延到鄰國，可能會引發地區危機。
這一切本來是可以避免的。 尚未批准針對蘇丹伊波拉病毒的有效疫苗或治療方法。 如果世界從以前的伊波拉疫情和 COVID-19 中吸取教訓，疫苗本可以在疫情開始時準備好進行臨床測試。事實是它們並不存在這是的全球性的失敗。
儘管面對 COVID-19 聯合起來生產數十億劑疫苗，但在首先開發疫苗以預防疾病時，世界仍在沉睡。 即使技術可用，市場仍然沒有動力提供可以預防疾病爆發的疫苗。 如果我們連針對已知的嚴重威脅（例如伊波拉病毒）的疫苗都不能準備好，那麼未來未知的大流行威脅還有什麼希望呢？
為在烏干達戰勝伊波拉病毒，資助在賴比瑞亞行之有效的措施
七年前，我在《自然》雜誌的專欄中警告過這個問題（S. Berkley Nature 519, 263; 2015）。 然而，儘管 COVID-19 敲響了警鐘，但這仍然是我們大流行病防範盔甲中最大的漏洞之一。
有了針對毀滅性疾病的有效可用疫苗，政府可以透過接觸者追踪和環形疫苗接種來防止升級：在伊波拉病毒的情況下，每個感染者的幾十個接觸者可能會接種疫苗。 但是，生產預防傳播所需的少量劑量對製藥公司來說是無利可圖的，捐助國政府也不願意將資金浪費在可能永遠不會使用的預防性疫苗上。
很難描述「短視」這種情況。 以每批幾百萬美元的價格製備預防性疫苗應被視為一項小保險，以避免重蹈世界剛剛在 COVID-19 上花費的 12 萬億美元的覆轍。
市場對疫苗的支持失敗應該讓每個人都感到擔憂，因為未來大流行的風險正在增加。 即使 COVID-19 繼續傳播，在特定年份仍有 2% 的機會爆發新的大流行病。 氣候變化、人口增長、城市化和人口遷移都有助於疫情更快地傳播和升級。
我們最好的防禦措施是準備好疫苗，以便在災難襲來時使用。 世界衛生組織列出了九種具有大流行潛力的優先病原體，包括嚴重急性呼吸系統綜合症 (SARS) 和伊波拉病毒，以及代表一種可能的、尚未發現的病原體的「X 病」。 所有這九種都值得全力以赴：透過動物模型和早期臨床試驗階段開發幾種候選疫苗； 已準備好在爆發時立即進行測試的經過品質測試的小瓶疫苗； 如果疫苗被證明有效，則儲備足夠的劑量來控制疾病。 對於X病，應準備一套病毒載體和信使RNA傳遞系統，攜帶證明對疾病有效的抗原序列，並儘可能完成製造和臨床試驗。 透過提前進行大量臨床前和臨床工作，我們可以在需要時盡可能準備好劑量。
mRNA 疫苗能否改變對抗伊波拉病毒的鬥爭？
怎樣才能最終促成改變，讓我七年後不再寫這篇文章？ 需要明確的是，我們已經走了很遠，從幾乎不談論這個問題到生活在每天都強調其相關性的大流行病中。 我樂觀地認為心態正在發生變化。
關鍵的第一步是建立一個充分的、公共補貼的市場。 這將在 G20 各國政府的支持下實現協調一致的全球戰略，以推動生產預防流行病疫苗所需的研究、開發和靈活的小規模製造，即使正如我們所希望的那樣，它們並不需要。
富裕國家應該帶頭。 他們應確保設在奧斯陸的流行病防範創新聯盟 (the Coalition for Epidemic Preparedness Innovations, CEPI) 和設在紐約市的國際愛滋病疫苗倡議 (the International AIDS Vaccine Initiative, IAVI) 等機構獲得充足的資金來開展這項工作，這將涉及密切合作，與政府研究機構以及全球疫苗免疫聯盟、疫苗聯盟和世界衛生組織合作。
對於蘇丹埃博拉病毒，在 CEPI、IAVI、美國國家衛生研究院、美國生物醫學高級研究與發展局等機構的推動下，已在早期測試中確定了三種候選疫苗。 上週，烏干達收到了第一批用於預定試驗的疫苗。 但對於已經死亡的 56 人和已感染的 142 人，試驗來得太遲了——而且由於目前沒有新病例，它們可能來不及確定疫苗的有效性。
COVID-19 帶來了疫苗開發的復興。 許多疾病的新疫苗正在研製中。 我們有機會利用最新的方法和緊迫感。 馬跑了之後，我們不能繼續關上馬厩的門。 如果我們繼續依賴僅在流行病爆發後基於市場才生產數百萬劑的模式，那麼我們就已經失敗了。
自然 612, 377 (2022) ； doi: https://doi.org/10.1038/d41586-022-04423-8
利益兢爭：S.B. 創立了 IAVI，並在 CEPI 的研發委員會任職。
Even after COVID, the world’s vaccine strategy is failing
Seth Berkley / WORLD VIEW / 13 December 2022 / Nature
Without a global, publicly funded strategy, the market will fail to deliver vaccines to stop pandemics before they surge.
Four weeks ago, I visited Mulago National Referral Hospital, in Kampala, where I used to work. Today, it is home to one of Uganda’s Ebola isolation wings. During my visit, I witnessed some of the challenges that the government and health-care workers were facing to contain this terrible outbreak without the most effective tool there is: vaccines. The Sudan strain of ebolavirus has killed 56 people and spread to 9 districts in Uganda, including the capital city of 2 million people and regions that border other nations. If it spills into neighbouring countries, it could trigger a regional crisis.
All of this could have been avoided. No effective vaccines or treatments have been approved against Sudan ebolavirus. If the world had learnt its lesson from previous Ebola outbreaks and COVID-19, vaccines could have been ready for clinical testing at the outbreak’s start. The fact that they aren’t is a global failure.
Despite rallying to produce billions of doses of vaccines in the face of COVID-19, when it comes to developing vaccines to prevent a disease in the first place, the world is still asleep at the wheel. There is still no incentive for markets to deliver vaccines that can prevent outbreaks, even when the technology is available. If we can’t even have vaccines ready for known severe threats such as Ebola, then what hope is there for future unknown pandemic threats?
To beat Ebola in Uganda, fund what worked in Liberia
I warned about this problem seven years ago in a column in Nature (S. Berkley Nature 519, 263; 2015). Yet despite the COVID-19 wake-up call, this remains one of the biggest chinks in our pandemic-preparedness armour.
With effective, available vaccines against devastating diseases, governments could prevent escalation through contact tracing and ring vaccination: in the case of Ebola, perhaps a few dozen contacts of each infected person could be vaccinated. But producing the small number of doses needed to prevent spread is not profitable for drug companies, and donor governments are reluctant to waste money on preventive vaccines that might never get used.
‘Short-sighted’ hardly describes the situation. Preparing preventive vaccines for a few million dollars per batch should be seen as a small insurance policy to avoid a repeat of the US$12 trillion the world just spent on COVID-19.
The market’s failure to support vaccines should worry everyone, because the risk of future pandemics is growing. Even as COVID-19 continues to spread, in a given year there is a 2% chance of a new pandemic outbreak. Climate change, population growth, urbanization and human migration all help outbreaks to spread and escalate more rapidly.
Our best defence is having vaccines ready to use the moment disaster strikes. The World Health Organization keeps a list of nine priority pathogens with pandemic potential, including severe acute respiratory syndrome (SARS) and Ebola, as well as ‘disease X’, which represents a possible, as-yet-undiscovered pathogen. All nine deserve a full effort: development of several candidate vaccines through the animal-model and early clinical testing stages; vialed and quality-tested vaccines that are ready for immediate testing in an outbreak; and stockpiling of enough doses to control the disease if the vaccine is shown to be efficacious. For disease X, a set of viral vectors and messenger RNA delivery systems should be ready to carry the sequences of whichever antigens prove effective against the disease, and the manufacturing and clinical trials should be worked through as far as possible. By doing much of the preclinical and clinical work in advance, we can have doses as close to ready as possible when we need them.
Can mRNA vaccines transform the fight against Ebola?
What will it take to finally catalyse change, so that I’m not writing this again seven years from now? To be clear, we have come far, from hardly talking about this issue to living through a pandemic that daily highlights its relevance. I am optimistic that a change in mindset is in view.
A key first step is the establishment of an adequate, publicly subsidized market. This will enable a coordinated global strategy with the support of G20 governments to drive the research, development and flexible small-scale manufacturing needed to produce vaccines to prevent epidemics, even if, as we hope, they will not be needed.
Wealthy countries should take the lead. They should ensure that agencies such as the Coalition for Epidemic Preparedness Innovations (CEPI), based in Oslo, and the International AIDS Vaccine Initiative (IAVI), based in New York City, are fully funded to do this work, which will involve close collaboration with government research agencies as well as Gavi, the Vaccine Alliance, and the WHO.
For Sudan ebolavirus, three candidate vaccines have been identified in early testing, following research and development driven by CEPI, IAVI, the US National Institutes of Health, the US Biomedical Advanced Research and Development Authority and others. Last week, Uganda received the first vaccine shipment for scheduled trials. But for the 56 people who have died and the 142 who have been infected, trials will come too late — and, as there are currently no new cases, they might be too late to determine vaccine efficacy.
COVID-19 has brought a renaissance in vaccine development. New vaccines are in the pipeline for many diseases. We have an opportunity to capitalize on the latest methods and a sense of urgency. We can’t continue closing the stable door after the horse has bolted. If we keep relying on a market-based model that churns out millions of doses only after an epidemic is under way, then we have already failed.
Nature 612, 377 (2022)
doi: https://doi.org/10.1038/d41586-022-04423-8
COMPETING INTERESTS
S.B. founded IAVI and served on the research and development committee of CEPI.