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How COVID-19 Immunity Holds Up Over Time

Posted on by Lawrence Tabak, D.D.S., Ph.D.

Antibody protection. Graph showing gradient of many antibodies early and less as time goes on

More than 215 million people in the United States are now fully vaccinated against the SARS-CoV-2 virus responsible for COVID-19 [1]. More than 40 percent—more than 94 million people—also have rolled up their sleeves for an additional, booster dose. Now, an NIH-funded study exploring how mRNA vaccines are performing over time comes as a reminder of just how important it will be to keep those COVID-19 vaccines up to date as coronavirus variants continue to circulate.

The results, published in the journal Science Translational Medicine, show that people who received two doses of either the Pfizer or Moderna COVID-19 mRNA vaccines did generate needed virus-neutralizing antibodies [2]. But levels of those antibodies dropped considerably after six months, suggesting declining immunity over time.

The data also reveal that study participants had much reduced protection against newer SARS-CoV-2 variants, including Delta and Omicron. While antibody protection remained stronger in people who’d also had a breakthrough infection, even that didn’t appear to offer much protection against infection by the Omicron variant.

The new study comes from a team led by Shan-Lu Liu at The Ohio State University, Columbus. They wanted to explore how well vaccine-acquired immune protection holds up over time, especially in light of newly arising SARS-CoV-2 variants.

This is an important issue going forward because mRNA vaccines train the immune system to produce antibodies against the spike proteins that crown the surface of the SARS-CoV-2 coronavirus. These new variants often have mutated, or slightly changed, spike proteins compared to the original one the immune system has been trained to detect, potentially dampening the immune response.

In the study, the team collected serum samples from 48 fully vaccinated health care workers at four key time points: 1) before vaccination, 2) three weeks after the first dose, 3) one month after the second dose, and 4) six months after the second dose.

They then tested the ability of antibodies in those samples to neutralize spike proteins as a correlate for how well a vaccine works to prevent infection. The spike proteins represented five major SARS-CoV-2 variants. The variants included D614G, which arose very soon after the coronavirus first was identified in Wuhan and quickly took over, as well as Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529).

The researchers explored in the lab how neutralizing antibodies within those serum samples reacted to SARS-CoV-2 pseudoviruses representing each of the five variants. SARS-CoV-2 pseudoviruses are harmless viruses engineered, in this case, to bear coronavirus spike proteins on their surfaces. Because they don’t replicate, they are safe to study without specially designed biosafety facilities.

At any of the four time points, antibodies showed a minimal ability to neutralize the Omicron spike protein, which harbors about 30 mutations. These findings are consistent with an earlier study showing a significant decline in neutralizing antibodies against Omicron in people who’ve received the initial series of two shots, with improved neutralizing ability following an additional booster dose.

The neutralizing ability of antibodies against all other spike variants showed a dramatic decline from 1 to 6 months after the second dose. While there was a marked decline over time after both vaccines, samples from health care workers who’d received the Moderna vaccine showed about twice the neutralizing ability of those who’d received the Pfizer vaccine. The data also suggests greater immune protection in fully vaccinated healthcare workers who’d had a breakthrough infection with SARS-CoV-2.

In addition to recommending full vaccination for all eligible individuals, the Centers for Disease Control and Prevention (CDC) now recommends everyone 12 years and up should get a booster dose of either the Pfizer or Moderna vaccines at least five months after completing the primary series of two shots [3]. Those who’ve received the Johnson & Johnson vaccine should get a booster at least two months after receiving the initial dose.

While plenty of questions about the durability of COVID-19 immunity over time remain, it’s clear that the rapid deployment of multiple vaccines over the course of this pandemic already has saved many lives and kept many more people out of the hospital. As the Omicron threat subsides and we start to look forward to better days ahead, it will remain critical for researchers and policymakers to continually evaluate and revise vaccination strategies and recommendations, to keep our defenses up as this virus continues to evolve.


[1] COVID-19 vaccinations in the United States. Centers for Disease Control and Prevention. February 27, 2022.

[2] Neutralizing antibody responses elicited by SARS-CoV-2 mRNA vaccination wane over time and are boosted by breakthrough infection. Evans JP, Zeng C, Carlin C, Lozanski G, Saif LJ, Oltz EM, Gumina RJ, Liu SL. Sci Transl Med. 2022 Feb 15:eabn8057.

[3] COVID-19 vaccine booster shots. Centers for Disease Control and Prevention. Feb 2, 2022.


COVID-19 Research (NIH)

Shan-Lu Liu (The Ohio State University, Columbus)

NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Heart, Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development


  • J.D. says:

    Thank you Lawrence, very informative

  • Tana Kalnbach, RN, PHN says:

    Yes, we’ve known for well over a year the immunity from the disease was robust and long-lasting. The Johns Hopkins study came out a couple weeks ago confirming that. Reinfections were uncommon until Omicron where we saw an increase. We did notice, however, Omicron is much less dangerous. I work with thousands of students and hundreds of staff in a school district and experienced this first hand.

    • Norma Bruce says:

      Tana–do you mean the immunity is NOT robust and long-lasting? 1-6 months is hardly robust.

      • Arvind Kushwaha says:

        Exactly, the point. That means another shot at six months. What about T cell immunity. Why are we so concerned about antibody levels. Will repeated jabs not disable our immune system??

        • D Hart MD says:

          “Will repeated jabs not disable our immune system??”

          No, there is no evidence of that. A well-referenced article about that topic was published on February 4 of this year by FactCheck (dot org) titled “COVID-19 Booster Enhances Protection, Contrary to ‘Immune Fatigue’ Claims”

          • Tim says:

            So you believe FactCheck?

          • D Hart MD says:

            Tim, I neither believe nor disbelieve FactCheck. What I rely on is the credence (or lack thereof) of the information at the links in any article on FactCheck, as FactCheck does next to no original work of its own.

            As I noted in my comment to which you replied, the FactCheck article I mentioned is well-referenced, and it is the information at those links that I have read, evaluated, and deemed to be credible.

            To reject a FactCheck article out of hand without assessing its validity is intellectually lazy and is indicative of cognitive bias.

  • Steve White says:

    I understand researchers must use pseudoviruses and look at antibody levels for preliminary findings, but after over six months, for Delta variant, don’t we have data on whether or not people actually got sick, and how sick? And Omicron has not been around long, but the number of cases is huge. One would think meaningful conclusions could be made rapidly if the patients can be assessed immediately.
    I understand these are laymen’s questions and very smart people are working on this, so it may come across as just whining – but looking at the advice – or lack of firm advice- given by CDC, and how much it effects the country, it seems like a real problem – my kid’s schools were shutdown due to Omicron, and it appears to me the local county health department suppressed the data showing how low the danger from it is – if CDC was assessing new variants really fast – based, not on lab modeling findings, but rather who is sick and how sick – “So, Mr. Smith, you have Omicron, were you vaccinated? Were you previously infected? When? How sick did you get then? I need to know because I have to efile a report with CDC right now, and you need to file this report online, or from your phone, about your progress:”, we could get the information that Omicron was not so bad in a few days I would think. SOMEONE PLEASE CREATE AN APP, OR IF IT EXISTS, PLEASE CDC, PROMULGATE IT. s

    PS – and if a really bad variant comes along – or, God forbid yet a new very bad virus enters human population, perhaps we can find it and get data on it faster. In my view, all international travelers should be required to put an app on their cell phone and keep the phone on and with them when entering the US – I do not like government spying generally but we can put any requirements on visas we want, and for US citizens, I think a few weeks of monitoring is not too much to ask.

  • Dlw90 says:

    Why don’t you ever discuss naturally acquired immunity? Answer: Because it’s superior to vaccine-acquired immunity. Would be great to see the NIH address their purposeful blind spot.

    • D Hart MD says:

      I posted the comment below on another NIH article. I repeat it here as it seems relevant to your comment.

      The results of a study out of Qatar published in the New England Journal of Medicine on February 9, 2022 (“Protection against the Omicron Variant from Previous SARS-CoV-2 Infection”) examined the protective effect of SARS-CoV-2 infection-derived immunity against symptomatic reinfection by alpha, beta, delta and omicron variants. The reinfections occurred at a median of about 9 months after the initial infections.

      They found that the protective effect of previous infections ranged from about 86% to 92% for the pre-omicron variants, but only about 56% for protection against an infection by the omicron variant. Fortunately, the protection against severe to fatal disease was pretty good, about 88% for an omicron infection. That protection against severe to fatal disease also is about par for 3 doses of the mRNA vaccines.

      Those results probably are a bit better than one would be expected to see in some other countries, as the median age of the Qatari population is 32.3. In the USA, for example, the median age is 38.5. The median age of the world (as of 2020) is 31.

    • John Gleeson says:

      Not a comment, but a question- is it?
      Is the waning of vaccine acquired immunity actually mirrored by the waning of immunity of populations exposed to the original variant or the alpha variant?
      Supposedly South Africans in the Cape area have large numbers of people with natural immunity as well as vaccine acquired immunity with research groups in situ- this location may be a suitable site to do population studies rather than biochemical studies.
      My guess is that ,as you suggest, the NIH does have a blind spot, but it is not”purposeful”.

    • Y.L. says:

      Absolutely! It will be great to see ,we’re comin!

  • Christy Ratheal says:

    Will the Covid vaccine become an annual vaccine like the Influenza vaccine?

  • Grand Junction, Colorado says:

    When will we get data, on how well the boosters protect against COVID, study seems incomplete with out the third level

  • D. Kov says:

    well written and informative…thank you.

  • Janet Leeper says:

    Excellent information.

  • Isaka says:

    Thank you so much! It’s informative

  • Jeffrey P. says:

    If ACTIV-5 data is positive could a case be made that an additional study for Lenzilumab would not be needed? Between Live-air and ACTIV-5, safety data and outcomes of saving lives.

  • Camillyn Weber says:

    Regarding natural immunity, the last review article I found on the CDC science page was: Equivalency of Protection From Natural Immunity in COVID-19 Recovered Versus Fully Vaccinated Persons: A Systematic Review and Pooled Analysis by
    Mahesh B. Shenai , Ralph Rahme , Hooman Noorchashm . Their conclusion: “While vaccinations are highly effective at protecting against infection and severe COVID-19 disease, our review demonstrates that natural immunity in COVID- recovered individuals is, at least, equivalent to the protection afforded by complete vaccination of COVID- naïve populations. There is a modest and incremental relative benefit to vaccination in COVID-recovered individuals; however, the net benefit is marginal on an absolute basis. Therefore, vaccination of COVID- recovered individuals should be subject to clinical equipoise and individual preference.” This was published in October 2021. Is there a more recent review of the literature article available in regards to natural immunity?

    • D Hart MD says:

      Yeah, that was before Omicron even existed (or, at least, known to exist). Things have changed some since then.

      There was an excellent article published in Nature Medicine (January 19, 2022) titled “mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant.” It showed a near absence of neutralizing antibody activity against the Omicron variant in those who had recovered from previous SARS-CoV-2 infection, as well as in those who had received the 2 doses of the Pfizer vaccine. A booster dose of the vaccine to those previously infected or previously fully vaccinated, however, resulted in a significant increase of serum neutralizing activity against Omicron.

  • E.P.D. says:

    Yes, Science has evolved. I Love Group Think.

  • Karla says:

    Why were the PhIII studies with adenoviral vector for HIV discontinued? And how is that relevant to what happens with adenoviral vector based vaccines for covid given MOA? Were those lessons passed on to a new generation of researchers or were they taught that pubmed searches of anything more than 10 years old is not relevant?

  • Daniel B. says:

    When should old folks get a 4th shot?

  • Fahmida pathan says:

    This article is very helpful to know about the immunue system of COVID-19.Thanks Lawrence Tabak.

  • Mitchell says:

    Very helpful, very interesting. Thank you for sharing!

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