mRNA Vaccines May Pack More Persistent Punch Against COVID-19 Than Thought
Posted on by Dr. Francis Collins
Many people, including me, have experienced a sense of gratitude and relief after receiving the new COVID-19 mRNA vaccines. But all of us are also wondering how long the vaccines will remain protective against SARS-CoV-2, the coronavirus responsible for COVID-19.
Earlier this year, clinical trials of the Moderna and Pfizer-BioNTech vaccines indicated that both immunizations appeared to protect for at least six months. Now, a study in the journal Nature provides some hopeful news that these mRNA vaccines may be protective even longer .
In the new study, researchers monitored key immune cells in the lymph nodes of a group of people who received both doses of the Pfizer-BioNTech mRNA vaccine. The work consistently found hallmarks of a strong, persistent immune response against SARS-CoV-2 that could be protective for years to come.
Though more research is needed, the findings add evidence that people who received mRNA COVID-19 vaccines may not need an additional “booster” shot for quite some time, unless SARS-CoV-2 evolves into new forms, or variants, that can evade this vaccine-induced immunity. That’s why it remains so critical that more Americans get vaccinated not only to protect themselves and their loved ones, but to help stop the virus’s spread in their communities and thereby reduce its ability to mutate.
The new study was conducted by an NIH-supported research team led by Jackson Turner, Jane O’Halloran, Rachel Presti, and Ali Ellebedy at Washington University School of Medicine, St. Louis. That work builds upon the group’s previous findings that people who survived COVID-19 had immune cells residing in their bone marrow for at least eight months after the infection that could recognize SARS-CoV-2 . The researchers wanted to see if similar, persistent immunity existed in people who hadn’t come down with COVID-19 but who were immunized with an mRNA vaccine.
To find out, Ellebedy and team recruited 14 healthy adults who were scheduled to receive both doses of the Pfizer-BioNTech vaccine. Three weeks after their first dose of vaccine, the volunteers underwent a lymph node biopsy, primarily from nodes in the armpit. Similar biopsies were repeated at four, five, seven, and 15 weeks after the first vaccine dose.
The lymph nodes are where the human immune system establishes so-called germinal centers, which function as “training camps” that teach immature immune cells to recognize new disease threats and attack them with acquired efficiency. In this case, the “threat” is the spike protein of SARS-COV-2 encoded by the vaccine.
By the 15-week mark, all of the participants sampled continued to have active germinal centers in their lymph nodes. These centers produced an army of cells trained to remember the spike protein, along with other types of cells, including antibody-producing plasmablasts, that were locked and loaded to neutralize this key protein. In fact, Ellebedy noted that even after the study ended at 15 weeks, he and his team continued to find no signs of germinal center activity slowing down in the lymph nodes of the vaccinated volunteers.
Ellebedy said the immune response observed in his team’s study appears so robust and persistent that he thinks that it could last for years. The researcher based his assessment on the fact that germinal center reactions that persist for several months or longer usually indicate an extremely vigorous immune response that culminates in the production of large numbers of long-lasting immune cells, called memory B cells. Some memory B cells can survive for years or even decades, which gives them the capacity to respond multiple times to the same infectious agent.
This study raises some really important issues for which we still don’t have complete answers: What is the most reliable correlate of immunity from COVID-19 vaccines? Are circulating spike protein antibodies (the easiest to measure) the best indicator? Do we need to know what’s happening in the lymph nodes? What about the T cells that are responsible for cell-mediated immunity?
If you follow the news, you may have seen a bit of a dust-up in the last week on this topic. Pfizer announced the need for a booster shot has become more apparent, based on serum antibodies. Meanwhile, the Food and Drug Administration and Centers for Disease Control and Prevention said such a conclusion would be premature, since vaccine protection looks really good right now, including for the delta variant that has all of us concerned.
We’ve still got a lot more to learn about the immunity generated by the mRNA vaccines. But this study—one of the first in humans to provide direct evidence of germinal center activity after mRNA vaccination—is a good place to continue the discussion.
 SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Turner JS, O’Halloran JA, Kalaidina E, Kim W, Schmitz AJ, Zhou JQ, Lei T, Thapa M, Chen RE, Case JB, Amanat F, Rauseo AM, Haile A, Xie X, Klebert MK, Suessen T, Middleton WD, Shi PY, Krammer F, Teefey SA, Diamond MS, Presti RM, Ellebedy AH. Nature. 2021 Jun 28. [Online ahead of print]
 SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans. Turner JS, Kim W, Kalaidina E, Goss CW, Rauseo AM, Schmitz AJ, Hansen L, Haile A, Klebert MK, Pusic I, O’Halloran JA, Presti RM, Ellebedy AH. Nature. 2021 May 24. [Online ahead of print]
COVID-19 Research (NIH)
Ellebedy Lab (Washington University, St. Louis)
NIH Support: National Institute of Allergy and Infectious Diseases; National Center for Advancing Translational Sciences
I am avoiding any vaccine because I am anemic, and using diet to recoup, more eggs and red meat. I live alone, therefore isolated in a nice condominium in Ecuador. I have read about VAERS and I realize that once I take a vaccine, I am at risk for heart illness and death. I have been diagnosed with sleep apnea by a study for the aging in Berkeley USB. Recently, possibly due to the anemia, I think I have been gradually becoming anemic for years, I have had hyper ventilation really bad. I was diagnosed by a medical doctor of internal medicine, and he pronounced anemia. I have had a new blood test and now an expat which I haven’t seen evaluated yet. Because of the breathing problems at 8,500 feet in the Andes mountains in Ecuador where I am retired on social security, I hesitate to take any vaccine, even the studies that confirm for women. I am 83 now, and I consider myself healthy of mind and body. I paint, grow a vegetable garden, avoid all sugar.
Suzanne, there may be good reasons in your case to avoid the vaccine, but VAERS is simply a raw data dump that (at best) reflects only a temporal relationship to the vaccine and not necessarily a causal relationship. There are reported adverse reactions (Bell palsy, for example) that, upon close examination, show no greater incidence in the vaccinated compared to the uninfected, unvaccinated population.
VAERS itself states, “VAERS reports alone cannot be used to determine if a vaccine caused or contributed to an adverse event or illness. The reports may contain information that is incomplete, inaccurate, coincidental, or unverifiable. In large part, reports to VAERS are voluntary, which means they are subject to biases.”
The best of health to you.
Spike proteings vs lymph nodes . . . Since we don’t know the answer to which is the more reliable, why would we not want to take the more cautious approach, and have a 6 month booster?
Is there any study on how long the J and J vaccine immunity lasts?
Thank you to all at NIH who have taken the responsibility to get us these two vaccines in such a rapid, safe way.
My biggest concern now is protecting our wonderful country from people who are dangerously infected (tested positive)and entering our borders … spreading this most dangerous virus.
This is a battle which needs to be fought on many different fronts in order to keep America healthy and safe.
I do not know if this is true, perhaps should not mention it – but, I have read that some of the top people – not Dr. Collins whose blog we are in here- but others – do not really believe travel bans work – if you look at our border controls, they were always on an honor system which seems highly unlikely to be followed- isolate yourself after you came across an ocean to get here? I think that is unrealistic.
IF we’d had effective travel bans, and maybe that is not possible, as some believe – but it we had kept out Delta and P1, it kind of looks like the epidemic here would be negligible – it might come back, but without those two variants, new cases per day might be under 1,000.
Little is being said about the Jansen vaccine which concerns me as my son and his wife received that one and live in a state not well vaccinated.
Thank you and your colleagues for all the work you’ve done on COVID-19, Long-COVID, and of course many other illnesses – and the work you are continuing to do.
I am glad to hear good news but I wish someone would give an update on modifications of the mRNA vaccines to deal with the new variants.
I see reports most infections are Delta now – and that the Israel health ministry reported efficacy, against any sign of infection, of only 64% for Pfizer/BionTech against Delta.
We were told the mRNA vaccines could be rapidly modified to target variants- but are also told Pfizer wants to give everyone a booster shot, of the same vaccine, in a few more months – why not a new vaccine targeted against Delta, and some others which are the main threats?
Pfizer’s Phase 3 study is around a year old now – I suspect they have data to back up their claim of a loss of efficacy – at the least, they know how much antibody levels fall after around a year. But my personal experience of the second Pfizer shot was I went to bed for the entire following day – slept and woke up with chills – and did not do much the day after – the third day I was back to normal – not too bad, well worth it, but taking a third shot would make me nervous- whereas, a new shot with different targets might not give any bad reaction, if I understand the science, because it would be a different antigen.
I agree that the data from Israel are really important. They seem to be the country doing the most careful analysis since they continue testing and genotyping all outbreaks. For vaccinated people, it seems to me that we are now more at risk of getting infected, even if our disease is mild or asymptomatic Therefore we can possibly spread the illness to unvaccinated children. We can also perhaps be at risk for long Covid. Both of are concerns to me even if they don’t seem to be at the top of the list for public health priorities.
So, I think boosters for the delta variant are important.
I wonder the age of these volunteers? Were any over 75 years old? How valid are the reports of people who were elderly or immunocompromised getting severe Covid19 following complete vaccination? If they are true why not take a booster? I am an 84 year old retired physician, partly trained at the NIH.
The oldest people who had lymph sampled were 52. They took blood from people up to age 73. The other study took bone marrow sample up to age 60 and blood up to age 69.
The mRNA vaccine technology it seems to me is just one of the many potential applications of this powerful preventive and therapeutic tool. It is amazing that you can now deliver instructions to cells in vivo to produce a therapeutic protein against any disease for which such a protein would be therapeutic. I think mRNA technology will be a bigger paradigm shift in disease therapeutics than penicillin was.
Yes, but the mRNA molecules are temporary and quickly broken down by the body. You have to deliver the mRNA to the specific cells that it will be useful for, and do it continually for it to keep having an effect.
I appreciate the concern, effort, and spending delegated to SARS COVID-19 immunity research, a gift to the well-being of the global population.
Though people with autoimmune diseases and a drug-induced reduction of B cells are a small minority of the population, we deserve to be part of the research to determine how effective the mRNA vaccine is for protecting us against Covid, and its mutation(s). I had my Pfizer Bio nTech mRNA vaccines in February and March, 2021, but all I know is my inoculation is not as strong as the average person’s, and no doctor will even venture a guess to tell me to what extent I am safe. Would a “booster” shot raise my resistance? Who knows? Researchers usually recruit volunteers from the under 60/65 age group, so there is no reliable scientific evidence to tell us anything about how an immune drug reacts/interreacts in an elderly senior’s body. Since the consequences of this virus are so serious, especially amongst the frail and elderly, perhaps it is time for researchers to establish a protocol to minimize risks, enabling elderly and those with compromised immune systems to contribute vital information to COVID-19 research. If nothing else, researchers will have a better understanding of the way an elderly body’s immune system engages with a drug like mRNA, which I’m betting is different than the average person’s immune system.
The ability to deliver instructions into human cells by a simple vaccination, which then transcribes and translates any polypeptide desired seems like an extraordinarily powerful new tool to potentially treat any disease treatable with a small, protein drug molecule. Couldn’t mRNA technology instruct cells to make a missing hormone, replace a faulty gene product or produce a protein that could quell an autoimmune response or stimulate an anti-cancer immune response?
I thank Dr. Collins for highlighting this important subject.
A relative of mine over eighty, already vaccinated with a second Pfizer booster three months ago, was given a booster for tetanus (associated with anti-diphtheria) a month ago, due to a small wound.
There are studies that indicate a protective effect towards severe forms of Covid-19 precisely on elderly people, given by the anti-tetanus and anti-diphtheria vaccination.
Is it possible that anti-tetanus and anti-diphtheria produce a synergistic effect on the persistence of immunity derived from the second booster of the mRNA vaccine for Covid-19? . . . Anti T-D is generally well tolerated and inexpensive.
What about us who have a compromised immune system and got no antibodies to the spike protein of the two shot series? Are we just a forgotten disposable group when discussing the lack of need for a booster shot!
In France they are giving people with certain immune conditions a third shot. In the USA, you can get more shots with a doctor’s approval. You might even be able to walk in to a Rite Aid and get one without a doctor’s note.
I live in Alabama. I have a prescription for a third shot. My pharmacist refuses to fill it and the State Dept of Health has denied me the shot because they say it’s not approved by the CDC. Alabama maintains a registry and their system shows my two Moderna shots.
I have read anecdotal reports of some who are immunocompromised who, like you, did not see a positive antibody response after completing the 2 shots of one of the mRNA vaccines, but who subsequently developed a robust response to vaccination with the J&J vaccine. One of those immunocompromised was a transplant surgeon.
I had a bad case of covid on Jan11 21 got out of hospital THE LAST DAY of Feb it really affected my lungs. My oxygen is now on 2 where it was 100 when I. Was at Vanderbilt icu from their I went to rehab don’t wear my oxygen all day. Just when I overdo. And I wear it at night. I am wondering if I can get the covi d shot. And which one should I try to take when I can have the shot. My doc says 6-9 months after I was sick.
How does your view comport with the observations from Israel? . . .
I received only 1 Pfizer vaccine in mid-January. A few minutes after having the vaccine, my throat became mildly numb, almost as if I sprayed Chloraseptic in my throat. I was able to breathe but it was definitely a bit more difficult to swallow. It lasted about 1.5 hours. An allergist advised me not to get the 2nd vaccine based on the CDC guidelines. I haven’t seen or heard anything about people like me…what options do we (I) have? I’m still very worried about getting the virus and have no idea what my immunity might be.
What’s with the headline? Who thought vaccines would wear off after 6-8 months?
My first vaccine was Pfizer then my second was Moderna at the insistence of the person administrating the vaccine , I said to her I was told when I booked it would be Pfizer? She said we don’t have it we are keeping it for the kids so you better take this one or you maybe out of luck take what you can get ? Now people are saying you shouldn’t mix the vaccines where before they were saying to go ahead .. so what’s happening now to the ones of us that had the mix of two different kinds?? Very worried 😟
Please don’t worry. Mixing vaccines is more effective than just taking one type. This is pretty common with vaccines because it gives your immune system broader exposure and helps it narrow down common aspects to look for. The reason they couldn’t *recommend* it is because there was not an official study about mixing Covid vaccine types. But now there was actually a small study in the UK (search for “mix and match vaccine study”) that proved the expected result.
What reasons does Pfizer claim support the need for a third shot and what is the status of research on those claims?
Note that the study that points to long-lasting immunity from the vaccines is based upon a prior study that points to the long-lasting immunity of naturally recovered individuals (SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans. Turner JS, Kim W, Kalaidina E, Goss CW, Rauseo AM, Schmitz AJ, Hansen L, Haile A, Klebert MK, Pusic I, O’Halloran JA, Presti RM, Ellebedy AH. Nature. 2021 May 24). As you point out, “The researcher based his assessment on the fact that germinal center reactions that persist for several months or longer usually indicate an extremely vigorous immune response that culminates in the production of large numbers of long-lasting immune cells, called memory B cells. Some memory B cells can survive for years or even decades, which gives them the capacity to respond multiple times to the same infectious agent.” Based on this, why have naturally recovered individuals not been treated the same as vaccinated individuals? The reason given is always that the vaccine will provide EXTRA antibodies to the S1 subsection of the RBD. Since we now know this is not the end all, be all of immunity against COVID, why is the naturally recovered population, which is AT LEAST 34 million in the United States but thought to be over 110 million, being discriminated against? Mandates that pertain to education and employment are being put in place with no regard to recovered status based on current guidance from the NIH and CDC. If the NIH and CDC wants to get more virus naive people vaccinated, they need to earn back the trust of the people, who view this disregard for basic logic as a reason for distrust.
I do, however, applaud you for not approving a booster shot at this point. Rather than just giving another dose of the same vaccines, it seems much more reasonable to develop new altered vaccines that instead focus on another aspect of the virus, such as the S2 subsection, which has been shown to be less mutatable.