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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 [1].

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 [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.


[1] 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]

[2] 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


  • John CW says:

    I have CLL. Your blog describing the Lymph Nodes as a repository of memory B cells is encouraging; however, with Chronic Lymphocytic Leukemia and recent reports specifically identifying CLL patients as “unprotected”, I hope you will report on research being conducted on any protection offered by T cells and if warranted, a recommendation on a third booster for immunocompromised people.

  • Benyounes says:

    Which vaccine getting when we are allergic to penicillin, some food (celery) and had an anaphylactic shock?

  • Ron Psimas says:

    Everyone needs to review the VAERS report on the Vaccines and make an intelligent decision on these experimental vaccines.

    • D Hart MD says:

      From the VAERS website itself, “…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.”

      And for the age groups for which the vaccines are recommended, the vaccines are authorized, not experimental. They ARE experimental (not authorized, not approved) for those younger than 12 (Pfizer) and for those younger than 18 (Moderna and J&J), that is true.

      • Te Gigahoo says:

        Would appreciate it if you would cite an authorative source for that statement.

        • D Hart MD says:

          As I wrote, it’s from the VAERS website itself.

          For some reason, this NIH blog website apparently does not allow the posting by commenters of links to websites, so you have to do a bit of searching yourself. Go to the VAERS website and click on the “VAERS Data” button. You will find the quote I used is in the first paragraph of the Disclaimer.

          • Jan says:

            Thanks, its very helpful to know. I’m looking for the study that claims to come out by NIH that having the virus gives better immunity than a vaccine. Would ike to see the methods section.

      • Orli Rudolph says:

        With all due respect they are not FDA approved for 12+ or adults. They are authorized for Emergency Use. There are no long term studies nor have studies ever been conducted on large groups of humans until this worldwide vaccination. Only time will tell.
        Anyone who reads through the VAERS website can see it is skewed to benefit those that do not want any unbiased reports on vaccines. It is a tedious process to report an adverse reaction to VAERS. The hundreds and thousands of people willing to go through the process to report is enough of a reason to question safety.

        • Barb R says:

          Considering all the foods and supplements that we ingest in our body, NONE FDA approved, your stance on a vaccine during a global pandemic seems frightfully awry. Have you considered what happens if you are wrong?

          • Christine says:

            Junk food and supplements are not mandated. Nor are they experimental. There are YEARS of results. You cannot compare this experiment to supplements, which by the way are WAY safer than this clinical trial.

  • Mickey says:

    Dr. Collins, that’s a very good news. Big fan of your research.

  • L Rogers says:

    If VAERS website is not the most reliable source of reporting data for adverse events or complications related to the COVID-19 vaccines, can someone provide a more reliable source?

    • Orli Rudolph says:

      There is no other accurate method of recording adverse reactions and deaths from vaccines. It’s unfortunate that you have to dig so deep to see what they don’t want us to know. There have been 1000’s of reported adverse reactions and parents that have had their children 12+ vaccinated who are suffering from heart inflammation and myocarditis. Most of these parents are learning the hard way that they have NO government support and the medical bills are growing daily. Also the pharmaceutical companies carry NO liability.

  • Donald DAVIS says:

    This seems to downplay the need for returning to masking and the need for a booster! Gets confusing when NIH says two things: a person with full vaccination has a strong immune response against variants, yet we need to mask and may need a booster! This double-speak is why people don’t listen when NIH talks.

  • Sheila V. says:

    i have skleraderma, got covid in early january, been a long hauler since. My body also reacted with a Leukamoid reaction and just now feeling like i am turning the corner to health. my EKG has also shown that i apparently have had a heart attack in the past???
    if i already have antibodies, and this virus did what it did to me, do really think someone like me still needs a vaccine? the censorship and flip flopping and not reporting of true data and statistical science is truly causing so much un-trustworthiness and confusion on what is right…. as i believe what is good for most may not be the answer for all. looking for a NON POLITICAL , and medical/scientific answer please.

    • D Hart MD says:

      If you have scleroderma, you likely have seen (or may still be seeing) a rheumatologist, the specialist who often deals with scleroderma and other connective tissue disorders. My advice would be to consult with her/him. If not (or in addition to), please discuss it with your personal physician who should know the pros and cons of your being vaccinated, given your personal circumstances. Good luck to you.

    • sep332 says:

      After being infected with Covid, getting a vaccine cuts your chances of getting re-infected by about half. Also, while data is still thin, there are many reports of long Covid being relieved after getting a vaccine.

  • Harold Gielow says:

    Data from Israel show that 95% of hospitalizations are of the fully vaccinated. Public Health England reports similar data. CDC reports that vaccinated individuals have the same viral loads on reinfection as the unvaccinated. All data seems to point to what has been experienced in all other corona virus animal vaccination trials – antibody dependent enhancement is a significant risk. Also, vaccinating during a pandemic creates the pressure for variant emergence. This is, in essence, a massive serial passage gain of function experiment. What is never talked about is that 72% of the US population have preexisting antibodies to a key constituent of the vaccines – polyethylene glycol. This was well known by the manufactures and regulators. Their excuse, as I have family in Pharma, is we did not have time to change it. So, they knew about the problem, never mitigated the risk, never warned the public, and pushed ahead. The problem is not primarily anaphylaxis, but vaccine ineffectiveness. If your body is mounting an immune response to the vaccine itself, the vaccine effectiveness will be diminished. We really have no clue about the effectiveness of the vaccines in our population. We do know, however, that there have been, at a minimum, 12,000 post vaccination deaths, approximately 38% of those deaths occurring in vaccinated who became ill within 48 hours of getting vaccinated. The list of negative side effects, other than death, are as long as your leg, including blood clots, blindness, thrombocytopenia, eosinophilia, cerebral venous sinus thrombosis, myocarditis, pericarditis, transverse myelitis, ataxia, guillain-barré syndrome, Bell’s Palsy and others. This while alternative medications are readily and cheaply available, like Ivermectin. Our health authorities have failed us or duped us.

  • Zuccheri Gianni says:

    The time of persistence of the vaccine mRNA, how do we come to say that it is quickly destroyed?

    In some cases cats can be infected by FlaviViruses (RNA) which are equipped with an enzyme, REVERSE TRANSCRITPTASIS: this would convert the viral RNA fragment into DNA, producing diseases in the animal, including neoplastic ones. These viruses can also harbor in humans, generally without consequences.
    The question :
    In case a person is an unaware carrier of a Flavivirus, by increasing the number of vaccine doses , the timing of presence of the Covid19 vaccine mRNA in the individual increases:
    with a higher probability of having the Reverse Transcriptase of a Flavivirus that translates the mRNA of the vaccine into DNA?
    In the event that an individual is a carrier of HCV (RNA Virus with its own reverse transcriptase) and at the same time also of Flavivirus, what could this happen with vaccine mRNA?

    Have you heard any communications about it?

    • D Hart MD says:

      Zuccheri Gianni, I will contribute what little I have to offer on this topic, since I investigated it on another website.

      The only information I’ve been able to find relates to HIV, a virus known to have reverse transcriptase. To date, there is no known instance in which HIV has altered a person’s DNA via the HIV’s reverse transcriptase, according to Paul Offit, MD (see “News & Views: 3 Questions You Will Get About the New mRNA Vaccines” on the website of the Children’s Hospital of Philadelphia).

      Secondly, mRNA is destroyed relatively quickly after it’s taken up by the cells, so it seems that would reduce the likelihood that a flavivirus would have the opportunity for the conversion, even if it were possible.

      Thirdly, if a vaccine’s mRNA could be converted by the reverse transcriptase of a flavivirus, I presume the mRNAs of SARS-CoV-2 could be as well.

      Finally, I’ve not been able to find any evidence that human flavivirus infections have been found to convert human RNA of any sort (mRNA, rRNA, tRNA) to DNA.

      As the saying goes, absence of evidence is not evidence of absence, but at this point it seems unlikely that flaviviruses pose a problem to humans. I hope others, though, with more expertise in these matters than I would offer their opinions as well.

      • Zuccheri Gianni says:

        I appreciate the precise analysis of the problem, supported by an excellent competence in the subject.
        I wonder if there is any news on this from the FDA and the CDC.
        As pointed out in the reply, in particular that even SARS-CoV-2 mRNA could itself be translated into DNA by Reverse Transcriptase: the consequences would be a planetary catastrophe after some time!
        It is therefore necessary to deepen the subject.
        I thank and cordially greet you

        • D Hart MD says:

          Zuccheri Gianni, you are welcome. Great to meet you (virtually) on this website, and thank you for your gracious reply.

          I agree; while there is no evidence that the concern you expressed is an actual present danger, I hope and trust that this issue is being actively investigated or monitored in some way. As you wrote so appropriately, if it should ever come to pass, it would be catastrophic.

  • Zuccheri Gianni says:

    Days ago I exposed the fears that the Flaviviruses housed in cats, if transmitted to humans in an asymptomatic form, produce interference with mRNA in those who are carriers (both vaccine and SARS-CoV-2). I confronted my colleague Dr. HART who, although with a different point of view, gave me good food for thought
    Could Flaviviruses, equipped with REVERSE TRANSCRIPTASIS, translate mRNA into DNA foreign to host cells?
    In a source provided by Dr. HART, I understand that the vaccine mRNA would persist up to about 10-14 days after inoculation.
    At this point, having found no documentation about it, I find articles indicating that cats may be affected by the SARS-CoV-2 virus. So in that case we would have the conditions I mentioned and studying them would lead to important results?

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