有些疫苗打了管一辈子，新冠疫苗为什么不行？
研究人员计算出了其他疫苗的保护阈值，但对新冠疫苗而言，这个重要数字至今仍是一个谜。
Some Vaccines Last a Lifetime. Here’s Why Covid-19 Shots Don’t.
Researchers have calculated a key number—the threshold of protection—for other vaccines. Covid-19’s is still a mystery.
新冠疫苗的保护效力为什么不能再持久一点？
麻疹疫苗可以帮助接种者终身免疫，水痘疫苗的效力可以持续10到20年，破伤风疫苗也可以管上十年或更久。然而，美国官员正在考虑是否批准完成了新冠疫苗接种的成年人在仅六个月后就接种加强针。
疫苗的作用在于通过接种形成本来在自然感染后才能获得的保护，并且没有重症或死亡风险。
“理想的疫苗让接种者即便接触了这种病毒，也不会被感染。”研究免疫应答的埃默里大学(Emory University)生物学教授拉斯托姆·安迪亚(Rustom Antia)说，“但并非所有疫苗都能达到这种理想的效果。”
Why don’t Covid-19 vaccinations last longer?
Measles shots are good for life, chickenpox immunizations protect for 10 to 20 years, and tetanus jabs last a decade or more. But U.S. officials are weighing whether to authorize Covid-19 boosters for vaccinated adults as soon as six months after the initial inoculation.
The goal of a vaccine is to provide the protection afforded by natural infection, but without the risk of serious illness or death.
“A really good vaccine makes it so someone does not get infected even if they are exposed to the virus,” said Rustom Antia, a biology professor at Emory University who studies immune responses. “But not all vaccines are ideal.”
他说，疫苗的保护分三个层级，包括：全面防止感染和传播，防止重症和降低传播，仅预防重症。
疫苗的效力取决于一连串因素：疫苗激发的免疫应答的强度，由此产生的抗体的衰减速度，病毒或病菌是否容易变异，以及感染发生的部位。
所谓保护阈值，是指足以预防生病的免疫水平。针对每种病毒，保护阈值都不相同，甚至连判定保护阈值的方式也存在差异。
The three tiers of defense, he said, include full protection against infection and transmission; protection against serious illness and transmission; or protection against serious illness only.
The effectiveness depends on the magnitude of the immune response a vaccine induces, how fast the resulting antibodies decay, whether the virus or bacteria tend to mutate, and the location of the infection.
The threshold of protection is the level of immunity that’s sufficient to keep from getting sick. For every bug, it’s different, and even how it’s determined varies.
“大体来说，也就是每毫升血液中抗体或中和抗体的水平。”俄勒冈健康与科学大学(Oregon Health & Science University)教授马克·斯利夫卡(Mark Slifka)说。
（T细胞也能起到保护作用，但抗体更容易测量。）
1942年，两名德国研究人员为了检验之前的动物实验结果，故意将自己暴露在毒素中，通过这种方式确定了针对破伤风的保护阈值为每毫升血液含有0.01国际单位抗体。
“其中一人在自己的大腿上注射了两剂致命的破伤风毒素，然后观察身体的变化。”斯利夫卡博士说，“另一人注射了三剂致命毒素。”
这两人都没有生病。
麻疹疫苗的阈值确定于1985年，当时一所大学的宿舍在一次献血活动后不久便暴露在该传染病环境中。后来，研究人员检测了献血学生血液中的抗体水平，最终确定，要预防麻疹，每毫升血液中的抗体需达到0.02国际单位。
“Basically, it’s levels of antibodies or neutralizing antibodies per milliliter of blood,” said Mark Slifka, a professor at Oregon Health & Science University.
(T-cells also contribute to protection, but antibodies are easier to measure.)
A threshold 0.01 international units per milliliter was confirmed for tetanus in 1942 when a pair of German researchers intentionally exposed themselves to the toxin to test the findings of previous animal studies.
“One of them gave himself two lethal doses of tetanus in his thigh, and monitored how well it went,” Dr. Slifka said. “His co-author did three lethal doses.”
Neither got sick.
A threshold for measles was pinned down in 1985 after a college dorm was exposed to the disease shortly after a blood drive. Researchers checked antibody concentrations in the students’ blood donations and identified 0.02 international units per milliliter as the level needed to prevent infection.
就这两种疾病而言，对疫苗反应的强度较高或抗体的衰减速度较慢，相应的结合即能产生持久的免疫应答：麻疹抗体的衰减速度较为缓慢；破伤风抗体的衰减速度更快，但疫苗促使人体产生的抗体数量远远超过了身体需求，从而抵消了抗体下滑的影响。
“在应对破伤风、白喉、麻疹和牛痘上，我们是幸运的。”斯利夫卡说，“我们已经知道了保护阈值是多少。随着时间推移，你发现抗体水平在下降，这时如果你知道保护阈值，就可以计算出疫苗效力大概可以持续多久。但就新冠病毒而言，我们不清楚它的保护阈值。”
从历史上看，最有效的疫苗使用的是复制型病毒，基本上可以做到终身免疫。
麻疹疫苗和水痘疫苗使用的就是复制型病毒。
非复制型疫苗和蛋白质疫苗（如破伤风疫苗）的效力没有那么久，但注入免疫佐剂（一种可以增强免疫反应的物质），疫苗效力可以得到强化。
破伤风疫苗和甲肝疫苗就要使用免疫佐剂。
With these diseases, the magnitudes of response to the vaccines combined with the antibodies’ rates of decay produce durable immune responses: Measles antibodies decay slowly. Tetanus antibodies decay more quickly, but the vaccine causes the body to produce far more than it needs, offsetting the decline.
“We’re fortunate with tetanus, diphtheria, measles and vaccinia,” Dr. Slifka said. “We have identified what the threshold of protection is. You track antibody decline over time, and if you know the threshold of protection, you can calculate durability of protection. With Covid, we don’t know.”
Historically, the most effective vaccines have used replicating viruses, which essentially elicit lifelong immunity.
Measles and chickenpox vaccines use replicating viruses.
Non-replicating vaccines and protein-based vaccines (such as the one for tetanus) don’t last as long, but their effectiveness can be enhanced with the addition of an adjuvant—a substance that enhances the magnitude of the response.
Tetanus and hepatitis A vaccines use an adjuvant.
强生公司(Johnson & Johnson)和阿斯利康(AstraZeneca)的新冠疫苗使用的是非复制型腺病毒，不含免疫佐剂。辉瑞(Pfizer)和Moderna的信使RNA(mRNA)新冠疫苗，其工作原理不同，不含有任何病毒。
为了绕开人体的免疫应答机制，病毒和病菌有时还会变异，这令事情变得更加复杂。
麻疹、腮腺炎、风疹以及水痘基本不会发生变异，但据《英国医学期刊》(British Medical Journal)，目前至少已发现八种SARS-CoV-2变体，这种病毒正是引发新冠肺炎的罪魁祸首。
“这确实让疫苗的起效机制变得更加复杂。”斯利夫卡说，“就好像慢慢地，你追踪的目标变得不止一个。流感病毒也会变异，我们的对策是每年研发一种新的流感疫苗，让它尽可能与当年新的流感毒株相匹配。”
流感疫苗的防护效力至少可以持续六个月。
The Johnson & Johnson and AstraZeneca Covid-19 vaccines use non-replicating adenovirus and don’t contain an adjuvant. The Pfizer and Moderna messenger RNA Covid-19 vaccines, which work differently, don’t contain any virus at all.
Complicating things further, viruses and bacteria that mutate to escape the body’s immune response are harder to control.
Measles, mumps, rubella and chickenpox hardly mutate at all, but at least eight variants of SARS-CoV-2, the virus that causes Covid-19, have been found, according to the British Medical Journal.
“It does make it more complicated for the vaccine to work,” Dr. Slifka said. “You’re chasing multiple targets over time. Flu also mutates. With flu, we’ve adjusted by making a new flu vaccine each year that as closely as possible matches the new strain of flu.”
Flu vaccines can offer protection for at least six months.
既然研制一种有效的疫苗来对付不断变化的病毒是如此复杂，那要不要暂且将此事搁在一边？如今有人已将希望寄托在另一策略上：依靠群体免疫来击败新冠病毒。但根据安迪亚博士的说法，考虑到新冠病毒感染人体的方式，这种办法挑战太大。
“对许多呼吸道感染来说，通过疫苗建立起长效群体免疫的可能性极低。”安迪亚说，“群体免疫只能持续一小段时间。它取决于病毒变化的速度，还取决于群体免疫减弱的速度。”
一个棘手之处在于，新冠病毒可以在上呼吸道和下呼吸道同时复制。
“我们的肺部和身体内部都有良好的血液循环，但鼻孔表面没有。”斯利夫卡说，“我们可以阻止严重疾病的发生，因为下呼吸道中存在抗体。”
但上呼吸道出现轻微感染的风险会一直存在。
放眼未来，新冠疫苗将继续更新迭代，以此对抗不同的病毒变种，另据帝国理工学院(Imperial College London)研究人员的说法，下一代新冠疫苗的研发重点可能也会侧重于增强鼻部潮湿表面和肺部的免疫力。
与此同时，想要抵御狡猾的病毒，也许还得再打一针疫苗才行。
Setting aside the complexities of crafting an effective vaccine to combat a shape-shifting virus, some hope has revolved around the possibility of defeating Covid-19 by achieving herd immunity, but, according to Dr. Antia, the way coronaviruses infect the body makes that challenging.
“Vaccines are very unlikely to lead to long-lasting herd immunity for many respiratory infections,” Dr. Antia said. “The herd immunity only lasts for a modest period of time. It depends on how fast the virus changes. It depends on how fast the immunity wanes.”
Part of the problem is that coronaviruses replicate in both the upper and lower respiratory tracts.
“We have good circulation in our lungs and body, but not on the surfaces of our nostrils,” Dr. Slifka said. “We can block severe disease because there are antibodies in the lower respiratory tract.”
But the risk of low-level infections in the upper respiratory tract can persist.
Moving forward, Covid-19 vaccines will be updated to combat variants of the virus, and according to researchers at Imperial College London, the next generation of vaccines might also focus on enhancing immunity in the moist surfaces of the nose and lungs.
In the meantime, avoiding the slippery virus might require another shot.
