A volunteer receives the second component of the nasal Sputnik V COVID-19 vaccine at Sechenov University Clinical Hospital No 2 in Moscow on Feb. 15, 2022.
2022年2月15日，在莫斯科謝切諾夫大學第二臨床醫院，一名志願者接受第二種成分的Sputnik V COVID-19鼻腔型疫苗(一種由俄羅斯Gamaleya 流行病學暨微生物學研究所，開發供COVID-19使用之腺病毒的病毒載體疫苗)。
BY JAMIE DUCHARME FEBRUARY 15, 2022 3:52 PM EST
When SARS-CoV-2, the virus that causes COVID-19, infiltrates the body, it typically enters through the nose or mouth, then takes root and begins replicating.
當導致2019冠狀病毒症(COVID-19：Coronavirus Disease-19)病毒的第二型嚴重急性呼吸系統徵候群-冠狀病毒(SARS-CoV-2：Severe Acute Respiratory Syndrome Coronavirus-2)滲入人體時，其通常通過鼻子或嘴巴進入，然後紮根並開始複製。
But what if it could never get a foothold in the upper airways? That’s the promise of nasal COVID-19 vaccines, which are meant to prevent infection by blocking the virus at its point of entry.
不過，倘若該種病毒永遠不會立足於上呼吸道，將會怎麼樣？那是必須藉由，在入口處阻擾此種病毒，來防止感染之鼻腔型COVID-19疫苗有指望的事。
There is not yet a nasal COVID-19 vaccine available in the U.S.—and it’s not clear if or when there will be—but multiple research teams in the U.S., including the National Institute of Allergy and Infectious Diseases, and abroad are working on them.
於美國，尚無一種可資使用的鼻腔型COVID-19疫苗(且目前尚並不清楚，是否或何時會有)。不過在美國，包括國家過敏暨傳染病研究所等，多支研究團隊及國外團隊，正針對這種疫苗進行研究。
Russian scientists are testing a nasal form of their Sputnik V vaccine in adult volunteers, and researchers in India have gotten approval for a Phase 3 trial.
俄羅斯科學家們正在成年志願者中，試驗其Sputnik V鼻腔型疫苗。而印度研究人員們，已經獲准進行第三期試驗。
Many researchers are excited about the prospect of nasal vaccines for COVID-19. “Yes with an exclamation point,” says Troy Randall, an immunologist at the University of Alabama at Birmingham, when asked if they’re worth exploring.
有關鼻腔型疫苗對COVID-19的前景，諸多研究人員是興奮的。當被問及它們是否值得探索時，美國阿拉巴馬大學伯明罕分校的免疫學家，Troy Randall宣稱：「是的！」
In countries like the U.S., where about 76% of people have had at least one dose of the COVID-19 vaccine, nasal vaccines would by default be used primarily as booster shots, and some research teams are studying them specifically in this capacity. But if they’re found to be effective and eventually authorized, they could also give young children and people who fear needles more options.
在諸多像大約76％的人，已經至少有一劑COVID-19疫苗的美國國家中，在默認情況下，鼻腔型疫苗會被使用，主要作為加強注射。因此，有些研究團隊正以此未經發掘的用途，進行研究它們。不過，倘若發現它們有效且最終獲得授權，則它們也可能給予幼兒及害怕針頭的人更多選擇。
There’s a long road ahead. While oral vaccines are fairly common, the only nasal vaccine cleared by the U.S. Food and Drug Administration to fight a respiratory pathogen is FluMist, which is used to prevent influenza among people ages 2 to 49.
前頭有漫長的路。儘管口服疫苗相當普遍，不過由美國食品暨藥物管理局審批，來對抗一種呼吸道病原體的唯一鼻腔型疫苗是FluMist。這被用來預防，2至49歲人群中的流行性感冒。
FluMist was in development for decades but was briefly taken off the market due to efficacy issues, which could foreshadow the challenges awaiting vaccine researchers working to create a nasal COVID-19 vaccine.
FluMist開發已經數十年。不過，由於功效問題，被短暫退出市場過。這可能預示著，諸多挑戰正等著，致力於開發鼻腔型COVID-19疫苗的疫苗研究人員們。
Still, researchers hope that nasal vaccines may one day do what even the highly effective mRNA vaccines made by Pfizer-BioNTech and Moderna have not: slow transmission enough to bring the pandemic to an end.
儘管如此，研究人員們期盼，有朝一日鼻腔型疫苗能做到，甚至由輝瑞-BioNTech及莫德納製造之高效mRNA疫苗，都沒有做到的效能：使傳播速度慢到，足以結束此大流行病。
Shot-in-the-arm COVID-19 vaccines introduce the body to genetic material from the SARS-CoV-2 virus, teaching the immune system what to do if it’s faced with the real thing. These shots have proven very good at preventing severe disease and death, but less adept at blocking infections—particularly against highly contagious Omicron.
注射於手臂的COVID-19疫苗，使人體接觸來自第二型嚴重急性呼吸系統徵候群-冠狀病毒(SARS-CoV-2：Severe Acute Respiratory Syndrome Coronavirus-2)的遺傳物質，來使免疫系統，倘若面對實際病毒時，知曉做什麼。此些注射已經證實，極善於預防嚴重疾病及死亡。不過，較不擅長阻擾感染，特別是對高度傳染性的Omicron。
Nasal vaccines could theoretically prevent many infections by conferring “local” immunity where it’s needed most: the nose. If it worked, a spritz would blanket the upper airways with defenses similar to those generated by the body after a brush with the actual virus, says Dr. James Crowe, director of Vanderbilt University Medical Center’s Vaccine Center.
理論上，鼻腔型疫苗能藉由，在最需要的地方(鼻子)賦予“局部”免疫力，來預防諸多感染。美國范德比爾特大學，醫學中心的疫苗中心主任，James Crowe博士表示，倘若其起作用，一道細噴流能，以類似身體接觸實際病毒後，產生的那些防禦力，覆蓋上呼吸道。
“You get the best immunity to virus pathogens by mimicking, to the greatest extent possible, the actual infection without causing disease,” Crowe says. “Stopping a virus in its tracks, right at the front door, is very attractive.”
Crowe宣稱：「藉由模仿實際感染而不引起疾病，人們能獲得對病毒病原體，達最大可能程度的最佳免疫力。在病毒路徑的正前門阻止它，是很具吸引力的。」
If done right, Crowe says, nasal vaccines could be highly effective—but developing them is difficult. They typically use live but weakened forms of a virus, which introduces a “Goldilocks” challenge, Crowe says.
Crowe表示，倘若被適當開發，鼻腔型疫苗會是高度有效。不過，開發它們很困難。通常，它們使用經削弱形式、卻活性的病毒。這引發了一種，“恰到好處(金髮姑娘)”的挑戰。
Weaken the virus too much and the vaccine won’t work; not enough, and it could overstimulate the immune system, leading to side effects. The balance has to be perfect. The nose is also a very different environment than the deltoid muscle, where shots are typically given. It’s a near-direct line to the brain, which clearly necessitates a different set of precautions, Crowe says.
削弱病毒太多，結果疫苗不會起作用；不夠，它可能過度刺激免疫系統，而導致副作用。必須是完美的平衡。鼻子也是一處，比通常被進行注射的肩部三角肌，非常不同的環境。Crowe表示，這是一條通到大腦，近乎直的線。顯然，這需要一套不同的預防措施。
The upper airways are also built to encounter foreign substances and thus may not respond as readily to a vaccine, says Benjamin Goldman-Israelow, an instructor at the Yale School of Medicine. He co-authored a recent study, which has not yet been peer-reviewed, that examined how mice responded to nasal versus injected COVID-19 vaccines.
美國耶魯大學醫學院講師，Benjamin Goldman-Israelow表示，上呼吸道也被形成，來對抗外來物質。因此，對疫苗可能並不那麼容易作出反應。他合撰了一項，探究小鼠對於鼻腔，對注射之COVID-19疫苗，如何作出反應，尚未經過同行評審的最新研究。
The research found that mice mounted a stronger immune response when they were injected first and then boosted with a nasal vaccine, as opposed to getting a nasal vaccine alone.
該項研究發現，與單獨接種鼻腔型疫苗相較下，當首先注射COVID-19疫苗，之後以一種鼻腔型疫苗加強時，小鼠發動了更強的免疫反應。
That may be because the upper airways are equipped with natural defenses against invading particles—they’re the body’s entry point for the outside world, after all—and thus do not always respond strongly when first introduced.
那或許是，因為上呼吸道配備了，對抗入侵粒子的天然防禦機制。畢竟，它們是人體供外部世界進入的入口點。因此，當首次被引入時，並非總是強烈作出反應。
“By giving that initial priming through the [injected] mRNA vaccine, we educate the immune system, so that by the time we give the intranasal boost, the immune system already knows to recognize this as foreign,” Goldman-Israelow says.
Goldman-Israelow宣稱：「藉由透過[注射的] mRNA疫苗，給予初始的啟動，來訓練免疫系統，以便當給予鼻腔型加強劑時，免疫系統已經知道將其識別為異物。」
Another rodent study by Yale researchers, published in December, found that mice vaccinated with a nasal flu shot were less likely to catch influenza than those that received an injected vaccine—a finding that may also apply to other respiratory diseases, such as COVID-19.
由耶魯大學研究人員們，於2021年12月，發表的另一項囓齒動物研究，發現施打鼻腔型流感疫苗的小鼠，比那些接受注射之疫苗的小鼠，較不可能罹患流行性感冒。這是一項，也可能適用於，諸如COVID-19等，其他呼吸道疾病。
Animal studies from other research teams have also shown promising signs that nasal vaccines may prevent infections, particularly when given as boosters.
諸多來自其他研究團隊的動物研究，也已經顯示，鼻腔型疫苗能預防感染，特別是被施予作為加強劑時，大有可為的跡象。
Of course, large clinical trials—some of which are underway in other countries—are necessary to know how a product will work in humans. “We cannot draw conclusions about whether a nasal COVID-19 vaccine is going to work or not work until we see the data,” says Dr. Hana Mohammed El Sahly, a professor of virology and microbiology at Baylor College of Medicine.
當然，大型臨床試驗(其中一些正在其他國家進行)對於了解，產品如何能在人體中，起作用是必要的。美國貝勒醫學院病毒學及微生物學教授，Hana Mohammed El Sahly博士宣稱：「在看到數據之前，他們無法獲得有關鼻腔型COVID-19疫苗，將起作用與否的結論。」。
Already, there have been setbacks. Last year, the biopharmaceutical company Altimmune stopped testing a nasal COVID-19 vaccine candidate due to disappointing trial results.
先前，已經有諸多挫折。去年，由於令人失望的試驗結果，生物製藥公司Altimmune，停止了一種候選鼻腔型COVID-19疫苗的試驗。
Nasal vaccines are difficult to get right. In the early 2000s, long before the COVID-19 pandemic, a nasal flu vaccine used in Switzerland was found to be associated with Bell’s palsy, a form of facial paralysis that is typically temporary. By the time that research was published, it was no longer in clinical use.
鼻腔型疫苗很難正確接種。於2000年代初期，早在COVID-19大流行病之前，瑞士使用的鼻腔型流感疫苗，被發現與貝爾氏麻痺症有關。那是一種，通常暫時性的臉部麻痺。到了那項研究被發表時，臨床上不再使用。
FluMist, the nasal flu vaccine used in the U.S. and first approved in 2003, hasn’t run into such safety issues, but it was briefly taken off the market due to efficacy problems. The U.S. Centers for Disease Control and Prevention’s vaccine advisory committee did not recommend its use in 2016,
於2003年首度獲准，在美國使用的鼻腔型流感疫苗，FluMist未曾遭遇此類安全問題。不過，由於功效問題，被短暫退出市場過。美國疾病控制暨預防中心的疫苗諮詢委員會，在2016年不建議使用它。
A reformulated version of the vaccine returned to market for the 2018-2019 season. In its current form, “it does seem to work, and the data are supportive of its continued use,” El Sahly says.
一種重新配製的疫苗版本重返了市場，供2018-2019季節使用。以目前的形式，El Sahly宣稱：「它似乎確實起作用，且數據支持其持續使用。」
Still, FluMist is not authorized for people who are 50 and older or younger than 2. It’s also not recommended for immunocompromised individuals and some people who have lung conditions such as asthma.
儘管如此，FluMist未被受權，供50歲及以上或2歲以下的人使用。它也不被建議，供免疫功能低下的個體，及一些具有哮喘等，肺部疾病的人使用。
That’s because it contains a live but weakened virus: an effective way to prompt an immune response, but one that can lead to potentially serious side effects in people with underlying conditions.
那是因為，它含有一種經削弱、卻是活性的病毒：這是一種誘發免疫反應的有效方法。不過，在具有潛在疾病的人中，它可能導致潛在上的嚴重副作用。
“It’s a balancing act,” Randall says. “You want the vaccine to be effective, but you don’t want it to really hurt or cause [too much] inflammation.”
Randall宣稱：「這是一種平衡舉措。人們希望疫苗有效，但不希望它事實上造成傷害，或引發[過多]炎症。」
Leaps in vaccine science have made it easier, if not easy, to find that balance. The Yale team working on nasal vaccines, for example, created a formula that does not contain an adjuvant (a material often added to vaccines to stoke a stronger response from the immune system) in hopes of reducing side effects.
疫苗科學方面的諸多躍進，已經使其較容易找到那種平衡(即使不容易)。譬如，在期盼減少副作用上，致力於鼻腔型疫苗的耶魯大學團隊創造了一種，不含佐劑(一種通常添加到疫苗中，以激發來自免疫系統之更強反應的物質)配方。
The pandemic also means there’s lots of interest in and money available for developing new vaccine candidates, which hasn’t always been the case.
But creating a vaccine to fight viruses that mutate frequently, like influenza and SARS-CoV-2, will always be challenging. That’s true whether researchers are developing a nasal vaccine or a shot in the arm, Randall says.
此次大流行病也意味著，有很多的參與及可資使用的資金供開發，情況並非總是如此的新候選疫苗。不過，研發一種對抗諸如流感及SARS-CoV-2等，經常變異的病毒，總是會具有挑戰性。Randall表示，那是無疑的，研究人員們是否開發鼻腔型或手臂注射型疫苗。
“We can ensure that the sequence that we selected is the one that actually ends up in the vaccine,” he says. But there’s no telling whether the sequence in the vaccine will be the one that “Mother Nature throws at us.” Such mismatches explain why the flu shot is far more effective in some years compared to others.
他宣稱：「他們能確保其選擇的序列，是實際最終於此種疫苗中的序列。」不過沒有敍述，於此疫苗中的序列，是否會是“大自然賦予人類”的那種。這種不匹配解釋了，為什麼流感疫苗，在某些年份中，遠比其他年份更有效。
So far, mRNA-based COVID-19 vaccines have held up well against new variants, providing strong protection against severe disease and death. Omicron, however, has been the best variant yet at dodging vaccine-acquired immunity, causing record-shattering numbers of cases and straining the health care system. That underscores the need for a tool that can prevent infections as well as severe disease.
迄今，在對抗新變異上，以mRNA為基礎的COVID-19疫苗，已經頗為承受住，能為嚴重疾病及死亡提供強有力的保護。不過，在躲避因疫苗獲得的免疫力上，Omicron一直是導致病例數破記錄，及給醫療保健系統帶來壓力的最佳變體。那強調了需要一種，除了嚴重疾病之外，也能預防感染的工具。
“Really, the goal is to reduce or even eliminate transmission,” says Tianyang Mao, a graduate student at the Yale School of Medicine and co-author of the study on booster nasal vaccines for COVID-19.
該項針對COVID-19鼻腔型加強劑疫苗研究的合撰人，美國耶魯大學醫學院研究生，Tianyang Mao宣稱：「其實，目標是減少或甚至消除傳播。」
Two years into the COVID-19 pandemic, the need is clear. But Yale’s Goldman-Israelow says his team is motivated to create a nasal vaccine not only for this pandemic, but also the next one.
COVID-19大流行病已經持續兩年，需求是顯而易見的。不過，耶魯大學的Goldman-Israelow表示，其團隊的動機是開發一種，不只供此次大流行病，而且也供下一次使用的鼻腔型疫苗。
Having the technology ready and waiting could significantly strengthen our country’s response the next time a new threat emerges—just as decades of work on mRNA vaccines came to fruition just in time to help with the COVID-19 pandemic.
技術準備就緒並等待，能顯著加強咱們國家，在下次出現新威脅時的反應。就如同數十年來，針對mRNA疫苗研究獲得的成果，正好及時協助對抗COVID-19大流行病。
If nasal vaccines had been available sooner to complement the COVID-19 vaccines we already have, he says, they could have “helped reduce transmission and help prevent the continuation of the pandemic that we’ve seen.”
他表示，倘若鼻腔型疫苗早點可資使用，來補足我們已經擁有的COVID-19 疫苗，則它們可能“有助於減少傳播及協助防止，我們已經遭遇之此次大流行病的持續。”
網址：https://time.com/6148257/nasal-vaccines-covid-19/?utm_medium=email&utm_source=sfmc&utm_campaign=newsletter+brief+default+ac&utm_content=+++20220217+++body&et_rid=197621499&lctg=197621499
翻譯：許東榮
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