輝瑞和莫德納疫苗可能產十分生持久的免疫力 - 有研究表示

Recently Yahoo News on-line reported the following:

Pfizer, Moderna Vaccines Likely to Produce Long-Lasting Immunity - A study Suggests

The New York Times - Apoorva Mandavilli

Mon., June 28, 2021, 11:33 a.m.

The vaccines made by Pfizer-BioNTech and Moderna set off a persistent immune reaction in the body that may protect against the coronavirus for years, scientists reported Monday.

The findings add to growing evidence that most people immunized with the mRNA vaccines may not need boosters, so long as the virus and its variants do not evolve much beyond their current forms — which is not guaranteed. People who recovered from COVID-19 before being vaccinated may not need boosters even if the virus does make a significant transformation.

“It’s a good sign for how durable our immunity is from this vaccine,” said Ali Ellebedy, an immunologist at Washington University in St. Louis who led the study, which was published in the journal Nature.

The study did not consider the coronavirus vaccine made by Johnson & Johnson, but Ellebedy said he expected the immune response to be less durable than that produced by mRNA vaccines.

Ellebedy and his colleagues reported last month that in people who survived COVID-19, immune cells that recognize the virus lie quiescent in the bone marrow for at least eight months after infection. A study by another team indicated that so-called memory B cells continue to mature and strengthen for at least a year after infection.

Based on those findings, researchers suggested that immunity might last for years, possibly a lifetime, in people who were infected with the coronavirus and later vaccinated. But it was unclear whether vaccination alone might have a similarly long-lasting effect.

Ellebedy’s team sought to address that question by looking at the source of memory cells: the lymph nodes, where immune cells train to recognize and fight the virus.

After an infection or a vaccination, a specialized structure called the germinal center forms in lymph nodes. This structure is an elite school of sorts for B cells — a boot camp where they become increasingly sophisticated and learn to recognize a diverse set of viral genetic sequences.

The broader the range and the longer these cells have to practice, the more likely they are to be able to thwart variants of the virus that may emerge.

“Everyone always focuses on the virus evolving — this is showing that the B cells are doing the same thing,” said Marion Pepper, an immunologist at the University of Washington in Seattle. “And it’s going to be protective against ongoing evolution of the virus, which is really encouraging.”

After infection with the coronavirus, the germinal center forms in the lungs. But after vaccination, the cells’ education takes place in lymph nodes in the armpits, within reach of researchers.

Ellebedy and his colleagues recruited 41 people — including eight with a history of infection with the virus — who were immunized with two doses of the Pfizer-BioNTech vaccine. From 14 of these people, the team extracted samples from the lymph nodes at three, four, five, seven and 15 weeks after the first dose.

That painstaking work makes this a “heroic study,” said Akiko Iwasaki, an immunologist at Yale. “This kind of careful time-course analysis in humans is very difficult to do.”

Ellebedy’s team found that 15 weeks after the first dose of vaccine, the germinal center was still highly active in all 14 of the participants, and that the number of memory cells that recognized the coronavirus had not declined.

“The fact that the reactions continued for almost four months after vaccination — that’s a very, very good sign,” Ellebedy said. Germinal centers typically peak one to two weeks after immunization, and then wane.

“Usually by four to six weeks, there’s not much left,” said Deepta Bhattacharya, an immunologist at the University of Arizona. But germinal centers stimulated by the mRNA vaccines are “still going, months into it, and not a lot of decline in most people.”

Bhattacharya noted that most of what scientists know about the persistence of germinal centers is based on animal research. The new study is the first to show what happens in people after vaccination.

The results suggest that a vast majority of vaccinated people will be protected over the long term — at least, against the existing coronavirus variants. But older adults, people with weak immune systems and those who take drugs that suppress immunity may need boosters; people who survived COVID-19 and were later immunized may never need them at all.

Exactly how long the protection from mRNA vaccines will last is hard to predict. In the absence of variants that sidestep immunity, in theory immunity could last a lifetime, experts said. But the virus is clearly evolving.

“Anything that would actually require a booster would be variant-based, not based on waning of immunity,” Bhattacharya said. “I just don’t see that happening.”

People who were infected with the coronavirus and then immunized see a major boost in their antibody levels, most likely because their memory B cells — which produce antibodies — had many months to evolve before vaccination.

The good news: A booster vaccine will probably have the same effect as prior infection in immunized people, Ellebedy said. “If you give them another chance to engage, they will have a massive response,” he said, referring to memory B cells.

In terms of bolstering the immune system, vaccination is “probably better” than recovering from the actual infection, he said. Other studies have suggested that the repertoire of memory B cells produced after vaccination is more diverse than that generated by infection, suggesting that the vaccines will protect better against variants than natural immunity alone.

Ellebedy said the results also suggested that these signs of persistent immune reaction might be caused by mRNA vaccines alone, as opposed to those made by more traditional means, like Johnson & Johnson’s.

But that is an unfair comparison, because the Johnson & Johnson vaccine is given as a single dose, Iwasaki said: “If the J & J had a booster, maybe it will induce this same kind of response.”

Translation

科學家週一報告說，Pfizer-BioNTech(輝瑞-BioNTech) 和 Moderna (莫德納) 的疫苗在體內引發了持續的免疫反應，這種反應能在數年內抵禦冠狀病毒。

這些發現增加了越來越多的證據，表明大多數接受 mRNA 疫苗免疫的人可能不需要加強免疫，只要病毒及其變體的進化不會超出它們當前的形式 -- 一個不能保證的可能性。在接種疫苗之前已從 COVID-19 中康復的人, 即使病毒確實發生了重大變化， 也可能不需要加強劑。

領導這項在《自然》雜誌上發表的研究的聖路易斯華盛頓大學免疫學家Ali Ellebedy 說：“這是一個好兆頭，表明這種疫苗對我們有多持久的免疫力”。

該研究沒有考慮強生公司(Johnson & Johnson)生產的冠狀病毒疫苗，但 Ellebedy 表示，他預計它的免疫反應的持久性不如 mRNA 疫苗產生的。

Ellebedy 和他的同事上個月報告說，從 COVID-19 復原的人中，免疫細胞能夠識別在感染後至少八個月內, 在骨髓中處於靜止狀態的病毒。另一個團隊的一項研究表明，所謂記憶 B 細胞, 在感染後至少在一年内會繼續成熟和加強。

根據這些發現，研究人員認為，曾感染冠狀病毒並隨後接種疫苗的人, 他的免疫力可能會持續數年，甚至一生。但目前尚不清楚只單獨接種疫苗是否會產生類似的長期効果。

Ellebedy 的團隊試圖通過查看記憶細胞的來源來解決這個問題：淋巴結，免疫細胞在那裡受訓練以識別和對抗病毒。

受感染或接種疫苗後，一種稱為胚芽中心的專門結構在淋巴結中形成。這種結構是 B 細胞的各種精英學校:  一個新兵訓練營。在那裡它們變得越來越老練, 並學會識別多組不同的病毒基因序列。

這些細胞練習的範圍越廣、時間越長，它們就越有可能阻止會出現的變種病毒。

西雅圖華盛頓大學的免疫學家 Marion Pepper 說:“每個人總是關注病毒的進化 - 這表明示B 細胞亦做同一樣的事情”; “它將可防禦病毒的持續進化，這真的令人鼓舞。”

感染冠狀病毒後，肺部形成胚芽中心。但是在接種疫苗後，細胞的學習在腋窩的淋巴結中開始，腋窩的淋巴是在研究人員的可接觸範圍內。

Ellebedy 和他的同事招募了 41 人- 其中 8 人有病毒感染史 - 他們接種了兩劑輝瑞-BioNTech 疫苗。在第一次接種後的第 3、4、5、7 和 15 週，研究小組從其中的 14 人裏提取了淋巴結樣本。

耶魯大學免疫學家 Akiko Iwasaki 說，這項艱苦的工作使這項研究成為一項“英勇的研究”。 “在人類中進行這種仔細的時間過程分析是非常困難的。”

Ellebedy 的團隊發現，在第一劑疫苗接種後15 週，所有 14 名參與者的胚芽中心仍然高度活躍，識別冠狀病毒的記憶細胞數量並沒有減少。

Ellebedy 說: “事實上，接種疫苗後反應持續了近四個月- 這是一個非常非常好的跡象” 。胚芽中心通常在免疫接種後一到兩周達到峰值，然後減弱。

亞利桑那大學免疫學家 Deepta Bhattacharya 說：“通常四到六週後，剩下的就不多了。”但 mRNA 疫苗刺激的胚芽中心“仍在繼續，幾個月後，大多數人裏面並沒有大幅下降。”

Bhattacharya 指出，目前科學家對胚芽中心持久性的了解大部分是基於動物研究。這項新研究首次展示了接種疫苗後會在人發生什麼。

結果表明，絕大多數接種疫苗的人將受到長遠保護 - 至少可以抵禦現有的冠狀的病毒的變種。但老年人、免疫系統較弱的人, 以及服用抑制免疫藥物的人可能需要加強劑；那些在 COVID-19 康復後並隨後接受免疫接種的人, 可能永遠不需要加強劑。

很難預測 mRNA 疫苗的保護作用會持續多久。專家說，如果沒有出現能閃避免疫的變異，理論上免疫可以持續一生。但病毒顯然在進化中。

Bhattacharya 說： “任何真正需要加強劑的情況都是由於變異，而不是基於免疫力的減弱。”; “我並沒有看到減弱情況發生。”

感染冠狀病毒然後接種疫苗的人的抗體水平顯著提高，這很可能是因為他們的記憶 B 細胞（它負責產生抗體）在接種疫苗前有幾個月的時間進化。

好消息是：Ellebedy 說，疫苗加強劑的效果可能與免疫人群先前感染的效果相同。關於記憶 B 細胞他又說: “如果你再給它們一次對應病毒的機會，它們就會有很强大的反應” 。

他說，在增強免疫系統方面，接種疫苗“可能比從實際感染後恢復產生的更強”。其他研究表明，接種疫苗後產生的記憶 B 細胞庫比感染產生的更多樣化，這表明疫苗比單一的自然免疫能更好地抵禦變異。

Ellebedy 說，結果還表明，這些持續免疫反應的跡象只可能由 mRNA 疫苗引起，而不是由更傳統的方法, 如強生公司 (Johnson & Johnson) 製造的疫苗能引起。

但這是一個不公平的比較，因為強生疫苗是單劑給藥，Akiko Iwasaki說：“如果強生有加強劑，也許它會引起同樣的反應。”

       So, while it is only a very small scale study, several interesting points have been suggested. First, people who recovered from COVID-19 previously and be vaccinated again, he/she may not need boosters. Second, in these people, immunity caused by vaccination may last for years, possibly a lifetime. Anything that would actually require a booster would be variant-based, not based on waning of immunity.  Third, the signs of persistent immune reaction may be caused by mRNA vaccines alone, as opposed to those made by more traditional means, such as those by Johnson & Johnson.