- There’s more to immunity than just antibodies.
- The two arms of the immune system work together: innate and adaptive/acquired immunity.
- The immune system is not a one-man Rambo; rather, they’re a network of fighters.
- Antibody levels naturally decline over time, i.e. level decreases following infection/recovery and vaccination.
- Adaptive immunity set up to fight the virus kicks in, once it sees the pathogen again.
COVID-19 is now ranked the “Number 1 cause of excess death”. Alarmist reports about “waning” antibody levels on fully-vaccinated people paint a doomsday scenario — suggesting that vaccines and other known treatments such as monoclonal antibodies may be rendered completely useless in stopping the pandemic.
It's a compelling story line, but a false one.
The effects of antibody decline, measured in terms of "titres", are not yet fully understood, as the body's immune system is complex. The role played by antibodies, B cells, T cells and other components continue to undergo continual scientific scrutiny. Vaccines, too, continue to have their efficacy investigated in the midst of variants, and subsequent "booster" shots. Data on the longevity of antibodies continue to be sliced and diced. One study quoting Italian researchers states that antibodies can be detected in the blood of recovered COVID-19 patients for at least 8 months post-infection.
What experts say:
What’s the proof of antibody “waning” among people who are COVID-recovered/vaccinated?
Scientists at the Imperial College London tracked antibodies in 365,000 randomly-selected adults. Tests show that the antibody response to the virus that causes COVID-19 “wanes” over time. The analysis, based on finger-prick tests, found that the number of people testing positive dropped by 26.5% across the study period.
Another study shows a 50% drop in antibody titres every 36 days. The research paper published in the New England Journal of Medicine reported a “rapid decay” in specific anti-SARS-CoV-2 antibodies in COVID-recovered persons.
The Italian study, conducted by clinical researchers San Raffaele hospital in Milan and published in Nature Communications, also confirmed the reduction in neutralising antibodyies over time.
Will this “waning” mean greater vulnerability to more infectious variants?
The answer is unclear. Prof. Karol Sikora, Dean of the College of Medicine at the University of Birmingham, said there’s more to the body’s immune system than just antibodies.
“It means that the antibody response, as a primary immune rejection for foreign protein — in this case the virus — wanes a bit. We’ve known that since the beginning.”
This sort of negativity (waning of antibodies) in the newspapers, it’s billed as terribly negative. It may not be.
He explained that surveys of blood samples from patients show antibody levels in various communities reach a maximum level six weeks after infection, and then they fall.
“But the other immune mechanisms kick in, including T cells immunity, lymphocytes, white blood cells that target the virus, and various other things we understand even less well than T cells. So we don’t know what it means.”
“This sort of negativity in the newspapers, it’s billed as terribly negative. It may not be,” Dr Sikora told CGTN channel. “What really matters is, over a period of time, do we as a society build up immunity against the virus.”
Should you measure your antibody levels after getting a COVID-19 vaccine?
A New Scientist report published in March 2021 shows commercial tests that promise to measure your immune response are “not very useful” — at least for now.
One reason: immune response to a vaccine is more intricate than a straightforward number — known as titre — measured in terms of units per millilitre (u/mL).
What is the antibody level created by natural infection?
Between 1 u/mL to 1,000 u/mL.
James Monico, co founder of Testing for All, told New Scientist that in an evaluation of 225 samples, the antibody level created by natural infection appeared to be between 1 and 1,000 u/mL. It’s a very wide range: what’s clear, he said, is that some antibodies are better than none.
• They also detect a wide variety of pathogenic microbes. In addition to simply detecting the presence/absence of a pathogen, RT-PCR also reports cycle threshold (Ct) values.
• Ct is the thermal cycle number at which the fluorescent signal exceeds that of the background and, therefore, passes the threshold for positivity.
• The quantity of target nucleic acid in the sample is inversely proportional to the Ct — lower Ct values means higher viral loads. This allows clinicians to compare of relative levels (quantity) of a pathogen.
What do the antibody test kits show — or does not show?
The test kits out in the market check the level of antibodies that recognise the outer S-protein of the coronavirus. However, the current tests present certain key flaws:
- They are unable to tell how well the antibodies respond to the various strains of COVID.
- They are unable to tell the presence of other components of immunity — such as B-cells (which trigger production of further antibodies if they encounter the virus), and killer T-cells (which directly act against virus-infected cells and kill them).
- It's unknown how antibody levels co-relate with a person’s infectiousness — the ability to to transmit the virus to others.
Besides waning antibody titres, what’s the evidence of waning vaccine efficacy (VE)?
A number of studies were published on this subject. A team led by Dr Srinivas Nanduri of the US CDC and colleagues reported in Morbidity and Mortality Weekly (MMWR) journal (published on August 27, 2021), showing reduced vaccine efficacy over time.
Two doses of mRNA vaccines (administered during the period from March–May 2021) were 74.7% effective against infection among nursing home residents early in the vaccination program. Then VE declined significantly to 53.1%, during June–July 2021, when Delta variant became more dominant.
Also, in a study published September 7, 2021 in The Lancet, a research team led by Dr. Prerak V Juhani, of the Department of Internal Medicine, Yale School of Medicine, noted rare emerging reports of breakthrough infections, i.e. infection among vaccinated. The team noted, however that the incidence of severe or critical COVID-19 illness remains low in those who are fully vaccinated.
Do fewer antibodies against COVID result in less protection over time?
The answer is not straightforward. This is because antibodies comprise only a part of the body’s immune system. There's evidence that show very elderly and/or immunocompromised people generate fewer antibodies from vaccinationover; people who are aged >65s produce 50%-75% fewer antibodies. None of the studies looked closely into whether fewer antibodies leads to less protection over time. What’s clear, however, is that a great majority of people filling up hospitals are from the unvaccinated camp.
“We’re not seeing the hospitals filling up with vaccinated people," says Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Saskatoon, Canada, told Bloomberg. “What we’re seeing is mostly unvaccinated people still making up the bulk of the new cases.”
Should we be worried about waning levels of antibodies following vaccination?
Think of the immune system as a network, or an army — instead of a one-man Rambo. It has numerous components that work together. In general, the immune system is made up of two parts: innate immunity and adaptive – or acquired – immunity. Besides antibodies, there are also B cells and T cells that act as a team to defend the body from foreign invaders.
After an infection has been cleared, it's normal for levels of antibodies to taper off, say experts. It’s important to note, however, that while antibodies represent an key part of the immune system, it’s only one part of the body’s system of internal defences.
Waning antibodies will come back up again from your memory B cells if exposed.
Due to the increased dominance of the highly infectious Delta variant, emerging data increasingly show a slight decrease in protection from vaccinations. However, clinicians like antibodies are like an accordion: "They will come back up again from your memory B cells if exposed," said Dr Monica Gandhi an infectious disease expert at the University of California in San Francisco.
"Which is why, again and again, please do not only think of antibodies when you think of immune system - think of its complexity. You have adaptive immunity set up to fight virus if you see it again so very unlikely to be infectious to others for long," she added.
• Bone marrow: It is the factory of blood cells. It’s an extremely important component of the immune system because all the body’s blood cells (including T and B cells, or lymphocytes) originate in the marrow of our bones. B cells remain in the marrow to mature; T cells travel to the thymus.
• Thymus: The thymus is a gland (located above the heart and between the lungs, responsible for producing the hormone thymosin which, in turn, aids in the production of T cells.
While in the thymus, T cells multiply, acquire different antigen receptors, and differentiate into helper T cells and cytotoxic T cells. Also part of the immune system are various proteins (e.g., CD4+ T cells, CD8+ T cells), found and expressed in the surface of T cells.
The thymus is only active through puberty. Throughout puberty, the thymus will have produced all the T cells an individual needs.
What’s the role of CD+8 T cells in immune “memory”?
In a study published in March 2021, researchers found that a key player in the immune response to SARS-CoV-2 — the CD8+ T cell —remained active against the virus.
The study was conducted prior to the emergence of virus variants by researchers at the US National Institute of Allergy and Infectious Diseases (NIAID), who analysed blood samples from 30 people who recovered from COVID-19 (prior to the emergence of virus variants).
The research team was led by NIAID’s Andrew Redd, and included scientists from Johns Hopkins University School of Medicine. In their study of recovered COVID-19 patients, the researchers determined that SARS-CoV-2-specific CD8+ T-cell responses remained largely intact and could recognise virtually all mutations in the variants studied.
The researchers stated their finding showS T cell response in recovered individuals — and most likely in vaccinees — are largely not affected by the mutations found in variants of concern, and should offer protection against emerging variants.
That study, however, was small — 30 people — and needs a larger sample to confirm.
Scientists are unsure about the exact levels and composition of antibody and T-cell responses needed to achieve a good level of immunity and avoid an “immune escape”.
TYPES OF T CELLS
- CD4+ T helper (Th) cells: They interact with CD8+ T cells, which drive the cytotoxic response that kills cells infected with the virus.
- The CD8+ T cells: They directly recognise viral peptides presented at the surfaces of infected cells, causing apoptosis (a form of programmed cell death), thus preventing the virus from spreading further.
- Follicular helper T (TFH) cells: These are a specialised subset of CD4+ T cells that provide help to B cells through both cell-cell interactions and release of cytokines, leading to the production of antibodies by B cells. These neutralising antibodies can recognize whole viruses and act by blocking the virus from infecting cells.
- Alveolar macrophages: They recognise the neutralised viruses and the cells killed by the CD8+ T cells and clear them by phagocytosis. This then results in recovery from the viral infection.