Politicians have become more cautious about immunisation prospects. They are right to be
政治家們對免疫接種的前景變得更加謹(jǐn)慎，他們這樣做是正確的
Vaccines are simple in principle but complex in practice.
疫苗原理上簡單，實(shí)際上復(fù)雜
It would be hard to overstate the importance of developing a vaccine to Sars-CoV-2 – it’s seen as the fast track to a return to normal life. That’s why the health secretary, Matt Hancock, said the UK was “throwing everything at it”.
But while trials have been launched and manufacturing deals already signed – Oxford University is now recruiting 10,000 volunteers for the next phase of its research – ministers and their advisers have become noticeably more cautious in recent days.
Earlier this week, England’s deputy chief medical officer Jonathan Van-Tam said the words nobody wanted to hear: “We can’t be sure we will get a vaccine.”
Vaccines are simple in principle but complex in practice. The ideal vaccine protects against infection, prevents its spread, and does so safely. But none of this is easily achieved, as vaccine timelines show.
More than 30 years after scientists isolated HIV, the virus that causes Aids, we have no vaccine. The dengue fever virus was identified in 1943, but the first vaccine was approved only last year, and even then amid concerns it made the infection worse in some people. The fastest vaccine ever developed was for mumps. It took four years.
在科學(xué)家分離出引起艾滋病的 HIV 病毒30多年后，我們還沒有疫苗。登革熱病毒是在1943年被發(fā)現(xiàn)的，但是第一種疫苗直到去年才被批準(zhǔn)，即使在那時，人們還是擔(dān)心它會使一些人的感染更加嚴(yán)重。有史以來發(fā)展最快的疫苗是針對腮腺炎的?；怂哪甑臅r間。
Scientists have worked on coronavirus vaccines before, so are not starting from scratch. Two coronaviruses have caused lethal outbreaks before, namely Sars and Mers, and vaccine research went ahead for both. But none have been licensed, partly because Sars fizzled out and Mers is regional to the Middle East. The lessons learned will help scientists create a vaccine for Sars-CoV-2, but there is still an awful lot to learn about the virus.
科學(xué)家們之前已經(jīng)研究過冠狀病毒疫苗，所以并不是從零開始。兩種冠狀病毒曾引起過致命疫情，即非典型肺炎和中東呼吸綜合癥，疫苗研究對這兩種病毒都進(jìn)行了研究。但是沒有一種疫苗得到許可，部分原因是非典疫情消失了，而 Mers 是中東地區(qū)性疫苗。這些經(jīng)驗教訓(xùn)將有助于科學(xué)家研制 Sars-CoV-2疫苗，但是關(guān)于這種病毒還有太多東西需要了解。
A chief concern is that coronaviruses do not tend to trigger long-lasting immunity. About a quarter of common colds are caused by human coronaviruses, but the immune response fades so rapidly that people can become reinfected the next year.
Researchers at Oxford University recently analysed blood from recovered Covid-19 patients and found that levels of IgG antibodies – those responsible for longer-lasting immunity – rose steeply in the first month of infection but then began to fall again.
Last week, scientists at Rockefeller University in New York found that most people who recovered from Covid-19 without going into hospital did not make many killer antibodies against the virus.
“That’s what is particularly challenging,” says Stanley Perlman, a veteran coronavirus researcher at the University of Iowa. “If the natural infection doesn’t give you that much immunity except when it’s a severe infection, what will a vaccine do? It could be better, but we don’t know.” If a vaccine only protects for a year, the virus will be with us for some time.
愛荷華大學(xué)的資深冠狀病毒研究人員 Stanley Perlman 說: “這就是特別具有挑戰(zhàn)性的地方。”?！叭绻匀桓腥境鞘菄?yán)重感染，否則不會給你那么大的免疫力，那么疫苗能起什么作用呢？可能會更好，但我們不知道?！?如果一種疫苗只能保護(hù)一年，那么這種病毒將會伴隨我們一段時間。
The genetic stability of the virus matters too. Some viruses, such as influenza, mutate so rapidly that vaccine developers have to release new formulations each year. The rapid evolution of HIV is a major reason we have no vaccine for the disease.
So far, the Sars-CoV-2 coronavirus seems fairly stable, but it is acquiring mutations, as all viruses do. Some genetic changes have been spotted in the virus’s protein “spikes” which are the basis of most vaccines. If the spike protein mutates too much, the antibodies produced by a vaccine will effectively be out of date and might not bind the virus effectively enough to prevent infection.
Martin Hibberd, professor of emerging infectious diseases at the London School of Hygiene and Tropical Medicine, who helped identify some of the virus’s mutations, called them “an early warning”.
倫敦衛(wèi)生與熱帶醫(yī)學(xué)學(xué)院的新發(fā)傳染病教授 Martin Hibberd 幫助識別出了一些病毒的突變，他稱之為“早期警告”。
Another challenge: making any vaccine safe
另一個挑戰(zhàn)是: 使任何疫苗都是安全的
In the rush to develop a vaccine – there are now more than 100 in development – safety must remain a priority. Unlike experimental drugs for the severely ill, the vaccine will be given to potentially billions of generally healthy people.
This means scientists will have to check extremely carefully for signs of dangerous side-effects. During the search for a Sars vaccine in 2004, scientists found that one candidate caused hepatitis in ferrets. Another serious concern is “antibody-induced enhancement” where the antibodies produced by a vaccine actually make future infections worse. The effect caused serious lung damage in animals given experimental vaccines for both Sars and Mers.
這意味著科學(xué)家必須非常仔細(xì)地檢查危險副作用的跡象。在2004年尋找 Sars 疫苗的過程中，科學(xué)家們發(fā)現(xiàn)一種候選病毒會導(dǎo)致雪貂患上肝炎。另一個嚴(yán)重的問題是“抗體誘導(dǎo)增強(qiáng)” ，即疫苗產(chǎn)生的抗體實(shí)際上使未來的感染更加嚴(yán)重。這種影響在給予 Sars 和 Mers 實(shí)驗疫苗的動物中造成了嚴(yán)重的肺損傷。
John McCauley, director of the Worldwide Influenza Centre at the Francis Crick Institute, says it takes time to understand the particular challenges each vaccine throws up. “You don’t know the difficulties, the specific difficulties, that every vaccine will give you,” he says. “And we haven’t got experience in handling this virus or the components of the virus.”
弗朗西斯·克里克研究院全球流感中心主任 John McCauley 說，要理解每種疫苗帶來的特殊挑戰(zhàn)需要時間。他說: “你不知道每種疫苗都會給你帶來的困難和具體的困難?！??！拔覀冊谔幚磉@種病毒或這種病毒的組成部分方面沒有經(jīng)驗?！?/span>
We should ‘end up with something’ … but what does that mean?
我們最終應(yīng)該會得出一些東西... ... 但這意味著什么呢？
When the prime minister, Boris Johnson, told a No 10 press briefing that a vaccine was “by no means guaranteed”, his chief scientific adviser, Patrick Vallance, agreed, but added: “I’d be surprised if we didn’t end up with something.” Many scientists share that view.
In all likelihood, a coronavirus vaccine will not be 100% effective.
冠狀病毒疫苗很有可能不會100% 有效。
Those in development draw on at least eight different approaches, from weakened and inactivated viruses to technologies that smuggle genetic code into the recipient’s cells, which then churn out spike proteins for the immune system to make antibodies against.
Ideally, a vaccine will generate persistent, high levels of antibodies to wipe out the virus and also “T” cells to destroy infected cells. But each vaccine is different and today no one knows what kind of immune response is good enough.
“We don’t even know if a vaccine can produce an immune response which would protect against future infection,” says David Heymann, who led the response of the World Health Organization (WHO) to the Sars epidemic.
Early results from two frontrunner vaccines suggest they might have some use.
兩種領(lǐng)先疫苗的早期結(jié)果表明，它們可能有一定的用途。
The US biotech firm Moderna reported antibody levels similar to those found in recovered patients in 25 people who received its vaccine.
美國生物技術(shù)公司 Moderna 報告的抗體水平與25名接種了該公司疫苗的康復(fù)患者的抗體水平相似。
Another vaccine from Oxford University did not stop monkeys contracting the virus, but did appear to prevent pneumonia, a major cause of death in coronavirus patients.
If humans react the same way, vaccinated people would still spread the virus, but be less likely to die from it.
如果人類也有同樣的反應(yīng)，接種疫苗的人仍然會傳播病毒，但是死于病毒的可能性更小。
How well a vaccine works determines how it is used. Armed with a highly effective vaccine that protects for several years, countries could aim for herd immunity by protecting at least two-thirds of the population.
Coronavirus patients pass the virus on to three others, on average, but if two or more are immune, the outbreak will fizzle out. That is the best-case scenario.
More likely is we will end up with a vaccine, or a number of vaccines, that are only partially effective.
更有可能的是，我們最終會得到一種疫苗，或者一些疫苗，而這些疫苗只是部分有效。
Vaccines that contain weakened strains of virus can be dangerous for older people, but might be given to younger people with more robust immune systems to reduce the spread of infection.
Meanwhile, older people might get vaccines that simple prevent infections progressing to life-threatening pneumonia. “If you don’t have the ability to induce immunity, you’ve got to develop a strategy for reducing serious outcomes of infection,” says McCauley.
But partially effective vaccines have their own problems: a vaccine that doesn’t stop the virus replicating can encourage resistant strains to evolve, making the vaccine redundant.
Hopes for eliminating the virus start with a vaccine but do not end there. “If and when we have a vaccine, what you get is not rainbows and unicorns,” says Larry Brilliant, CEO of Pandefense Advisory, who led the WHO’s smallpox eradication programme. “If we are forced to choose a vaccine that gives only one year of protection, then we are doomed to have Covid become endemic, an infection that is always with us.”
消滅病毒的希望始于疫苗，但并不止于此?！叭绻覀冇辛艘呙?，你得到的就不是彩虹和獨(dú)角獸了，”世界衛(wèi)生組織天花根除計劃的領(lǐng)導(dǎo)者 Pandefense Advisory 的首席執(zhí)行官 Larry Brilliant 說?！叭绻覀儽黄冗x擇一種只能提供一年保護(hù)的疫苗，那么我們就注定會產(chǎn)生地方性流行病，這種感染會一直伴隨著我們。”
The virus will still be tough to conquer with a vaccine that lasts for years.
這種病毒仍然很難被持續(xù)數(shù)年研發(fā)的疫苗所征服。
“It will be harder to get rid of Covid than smallpox,” says Brilliant. With smallpox it was at least clear who was infected, whereas people with coronavirus can spread it without knowing. A thornier problem is that as long as the infection rages in one country, all other nations are at risk.
As David Salisbury, the former director of immunisation at the Department of Health, told a Chatham House webinar recently: “Unless we have a vaccine available in unbelievable quantities that could be administered extraordinarily quickly in all communities in the world we will have gaps in our defences that the virus can continue to circulate in.”
Or as Brilliant puts it, the virus will “ping-pong back and forth in time and geography”.
或者正如布里連特所說，這種病毒將會“在時間和地理上來回反復(fù)爆發(fā)”。
One proposal from Gavi, the vaccine alliance, is to boost the availability of vaccines around the world through an “advance market commitment”. And Brilliant believes some kind of global agreement must be hammered out now. “We should be demanding, now, a global conference on what we’re going to do when we get a vaccine, or if we don’t,” he says.
“If the process of getting a vaccine, testing it, proving it, manufacturing it, planning for its delivery, and building a vaccine programme all over the world, if that’s going to take as long as we think, then let’s fucking start planning it now.”
People will have to adapt – and life will change. Heymann says we will have to get used to extensive monitoring for infections backed up by swift outbreak containment. People must play their part too, by maintaining handwashing, physical distancing and avoiding gatherings, particularly in enclosed spaces. Repurposed drugs are faster to test than vaccines, so we may have an antiviral or an antibody treatment that works before a vaccine is available, he adds. Immediate treatment when symptoms come on could at least reduce the death rate.
Yuen Kwok-yung, a professor of infectious disease at the University of Hong Kong, has advised his government that all social distancing can be relaxed – but only if people wear masks in enclosed spaces such as on trains and at work, and that no food or drink are consumed at concerts and cinemas.
At restaurants, tables will have to be shielded from each other and serving staff will follow strict rules to prevent spreading the virus. “In our Hong Kong perspective, the diligent and correct use of reusable masks is the most important measure,” he says.
Sarita Jane Robinson, a psychologist who studies responses to threats at the University of Central Lancashire, says people are still adapting to the “new normal” and that without more interventions – such as fines for not wearing face masks – “we could see people drifting back to old behaviours”.
中央蘭開夏大學(xué)研究應(yīng)對威脅的心理學(xué)家 Sarita Jane Robinson 表示，人們?nèi)栽谶m應(yīng)“新常態(tài)” ，如果不采取更多干預(yù)措施——比如對不戴面罩者處以罰款——“我們可能會看到人們回歸舊習(xí)慣”。
We might become blase about Covid-19 deaths when life resumes and the media move on, but the seriousness of the illness will make it harder to ignore, she says.
One last possibility could save a lot of trouble. Some scientists wonder whether the common cold coronaviruses crossed into humans in the distant past and caused similar illness before settling down. “If the virus doesn’t change there’s no reason to think that miraculously in five years’ time it won’t still cause pneumonia,” says Perlman. “But that’s the hope: that we end up with a much more mild disease and you only get a bad cold from it.”
Heymann says it is too soon to know how the pandemic will pan out. “We don’t understand the destiny of this virus,” he says. “Will it continue to circulate after its first pandemic? Or will it, like some other pandemic viruses, disappear or become less virulent? That we do not know.”
