Politicians have become more cautious about immunisation prospects. They are right to be
政治家们对免疫接种的前景变得更加谨慎，他们这样做是正确的
Vaccines are simple in principle but complex in practice.
疫苗原理上简单，实际上复杂
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.
在科学家分离出引起艾滋病的 HIV 病毒30多年后，我们还没有疫苗。登革热病毒是在1943年被发现的，但是第一种疫苗直到去年才被批准，即使在那时，人们还是担心它会使一些人的感染更加严重。有史以来发展最快的疫苗是针对腮腺炎的。花了四年的时间。
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.
科学家们之前已经研究过冠状病毒疫苗，所以并不是从零开始。两种冠状病毒曾引起过致命疫情，即非典型肺炎和中东呼吸综合症，疫苗研究对这两种病毒都进行了研究。但是没有一种疫苗得到许可，部分原因是非典疫情消失了，而 Mers 是中东地区性疫苗。这些经验教训将有助于科学家研制 Sars-CoV-2疫苗，但是关于这种病毒还有太多东西需要了解。
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.
爱荷华大学的资深冠状病毒研究人员 Stanley Perlman 说: “这就是特别具有挑战性的地方。”。“如果自然感染除非是严重感染，否则不会给你那么大的免疫力，那么疫苗能起什么作用呢？可能会更好，但我们不知道。” 如果一种疫苗只能保护一年，那么这种病毒将会伴随我们一段时间。
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”.
伦敦卫生与热带医学学院的新发传染病教授 Martin Hibberd 帮助识别出了一些病毒的突变，他称之为“早期警告”。
Another challenge: making any vaccine safe
另一个挑战是: 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.
这意味着科学家必须非常仔细地检查危险副作用的迹象。在2004年寻找 Sars 疫苗的过程中，科学家们发现一种候选病毒会导致雪貂患上肝炎。另一个严重的问题是“抗体诱导增强” ，即疫苗产生的抗体实际上使未来的感染更加严重。这种影响在给予 Sars 和 Mers 实验疫苗的动物中造成了严重的肺损伤。
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 说，要理解每种疫苗带来的特殊挑战需要时间。他说: “你不知道每种疫苗都会给你带来的困难和具体的困难。”。“我们在处理这种病毒或这种病毒的组成部分方面没有经验。”
We should ‘end up with something’ … but what does that mean?
我们最终应该会得出一些东西... ... 但这意味着什么呢？
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.
冠状病毒疫苗很有可能不会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.
两种领先疫苗的早期结果表明，它们可能有一定的用途。
The US biotech firm Moderna reported antibody levels similar to those found in recovered patients in 25 people who received its vaccine.
美国生物技术公司 Moderna 报告的抗体水平与25名接种了该公司疫苗的康复患者的抗体水平相似。
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.
如果人类也有同样的反应，接种疫苗的人仍然会传播病毒，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，我们最终会得到一种疫苗，或者一些疫苗，而这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.”
消灭病毒的希望始于疫苗，但并不止于此。“如果我们有了疫苗，你得到的就不是彩虹和独角兽了，”世界卫生组织天花根除计划的领导者 Pandefense Advisory 的首席执行官 Larry Brilliant 说。“如果我们被迫选择一种只能提供一年保护的疫苗，那么我们就注定会产生地方性流行病，这种感染会一直伴随着我们。”
The virus will still be tough to conquer with a vaccine that lasts for years.
这种病毒仍然很难被持续数年研发的疫苗所征服。
“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”.
或者正如布里连特所说，这种病毒将会“在时间和地理上来回反复爆发”。
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”.
中央兰开夏大学研究应对威胁的心理学家 Sarita Jane Robinson 表示，人们仍在适应“新常态” ，如果不采取更多干预措施——比如对不戴面罩者处以罚款——“我们可能会看到人们回归旧习惯”。
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.”
