Nature
Hedi Ledford
Gerry Gajadharsingh writes:
“With so-called “Freedom Day” approaching, on Monday 19th of July, the increase in COVID-19 infection because of the Delta variant and talk of booster COVID-19 vaccines in September/October 2021 many patients are asking my opinion.
We know that many patients had a minimal spike protein antibody response (especially in the elderly and immunocompromised patients’ populations) after the first dose of either vaccine, but we saw many patients getting a much stronger/robust response after the second dose of vaccine. The maximum level of spike protein Ab’s measured by this test is >2500. Unfortunately, there are patients where even two doses of vaccine, simply does not seem to have worked, either by measuring spike protein antibody responses or more recently via T cell responses. These patients still need to be very careful to minimise their risk of infection.
There are also patients who are having concerning reactions to receiving the vaccine, especially if they have had a history of having a previous COVID-19 infection. And I’m not talking about the minimal risk of anaphylaxis or cardiomyopathy from the Pfizer vaccine or stroke from the Oxford/Astrazeneca vaccine.
Testing for immunity to COVID-19 after infection or importantly, now after COVID 19 vaccination, has come on leaps and bounds over the past 3 to 4 months.
In February 2021 we were able to offer a blood test to detect spike protein antibodies (Roche Laboratories via TDL) which seemed far more superior and specific compared to the total IgG antibody test we were able to offer last year. In June 2021, we were also able to offer a brand-new blood test looking at T-cell responses TSPOT (Oxford Immunotec Laboratories via TDL), post COVID-19 infection or postvaccination to see how well or not immunity is working in individual patients.
I suppose the question that we should be asking ourselves is why would one to do these tests?
COVID-19 vaccination started in December 2020 and the first 4 vulnerable groups (and healthcare workers) as defined by JCVI, would probably have had both doses by around April/May 2021. So it may be that for many of the patients in the vulnerable groups six months at least may well have elapsed before they are offered a booster. I think it would be useful to know whether they need a booster?
It is thought that immunity, as measured by spike protein antibody response, is likely to wane over time, even in those who have had a good response to the vaccine. The research below is looking at T-cell response to vaccination and it’s possible that even with decreasing antibody levels the innate part of her immune system which provokes T-cell responses can still remain quite reactive giving us protection to severe disease although T cells generally can’t stop infection happening.
For your reference I measure my spike protein antibody responses on a monthly basis and more recently my T-cell response (since this new test only became available in June 2021). Four months post my second dose, I still have >2500 spike protein antibodies and a reactive (positive) T cell response. But as you would expect, I tend to do lots of other things to try to support my own immune system, not simply relying on vaccination to give me some immunity.
So, if you’re interested in knowing your level of immunity either post COVID-19 infection or after receiving a COVID-19 vaccine please go to
https://www.thehealthequation.co.uk/covid-19-testing/
Both tests are blood tests and can be carried out via phlebotomy (taking a blood sample), during your routine consultation or having a specific appointment to have the sample taken. In addition, the spike protein antibody test can be done on a capillary blood sample (finger prick sample), by a sample kit which can be sent to your home for you to do the sample yourself and a post-paid package (24 hr Royal Mail tracked) directly back to TDL laboratory, where the tests are analysed.”
In the race against emerging coronavirus variants, researchers are looking beyond antibodies for clues to lasting protection from COVID-19.
Concerns about coronavirus variants that might be partially resistant to antibody defences have spurred renewed interest in other immune responses that protect against viruses. In particular, scientists are hopeful that T cells — a group of immune cells that can target and destroy virus-infected cells — could provide some immunity to COVID-19, even if antibodies become less effective at fighting the disease.
Researchers are now picking apart the available data, looking for signs that T cells could help to maintain lasting immunity.
“We know the antibodies are likely less effective, but maybe the T cells can save us,” says Daina Graybosch, a biotechnology analyst at investment bank SVB Leerink in New York City. “It makes sense biologically. We don’t have the data, but we can hope.”
Coronavirus vaccine development has largely focused on antibodies, and for good reason, says immunologist Alessandro Sette at the La Jolla Institute for Immunology in California. Antibodies — particularly those that bind to crucial viral proteins and block infection — can hold the key to ‘sterilizing immunity’, which not only reduces the severity of an illness, but prevents infection altogether.
That level of protection is considered the gold standard, but typically it requires large numbers of antibodies, says Sette. “That is great if that can be achieved, but it’s not necessarily always the case,” he says.
Killer cells
Alongside antibodies, the immune system produces a battalion of T cells that can target viruses. Some of these, known as killer T cells (or CD8+ T cells), seek out and destroy cells that are infected with the virus. Others, called helper T cells (or CD4+ T cells) are important for various immune functions, including stimulating the production of antibodies and killer T cells.
T cells do not prevent infection, because they kick into action only after a virus has infiltrated the body. But they are important for clearing an infection that has already started. In the case of COVID-19, killer T cells could mean the difference between a mild infection and a severe one that requires hospital treatment, says Annika Karlsson, an immunologist at the Karolinska Institute in Stockholm. “If they are able to kill the virus-infected cells before they spread from the upper respiratory tract, it will influence how sick you feel,” she says. They could also reduce transmission by restricting the amount of virus circulating in an infected person, meaning that the person sheds fewer virus particles into the community.
T cells could also be more resistant than antibodies to threats posed by emerging variants. Studies by Sette and his colleagues have shown that people who have been infected with SARS-CoV-2 typically generate T cells that target at least 15–20 different fragments of coronavirus proteins1. But which protein snippets are used as targets can vary widely from person to person, meaning that a population will generate a large variety of T cells that could snare a virus. “That makes it very hard for the virus to mutate to escape cell recognition,” says Sette, “unlike the situation for antibodies.”
So when laboratory tests showed that the 501Y.V2 variant identified in South Africa (also called B.1.351) is partially resistant to antibodies raised against previous coronavirus variants, researchers wondered whether T cells could be less vulnerable to its mutations.
Early results suggest that this might be the case. In a preprint published on 9 February, researchers found that most T-cell responses to coronavirus vaccination or previous infection do not target regions that were mutated in two recently discovered variants, including 501Y.V22. Sette says that his group also has preliminary evidence that the vast majority of T-cell responses are unlikely to be affected by the mutations.
If T cells remain active against the 501Y.V2 variant, they might protect against severe disease, says immunologist John Wherry at the University of Pennsylvania in Philadelphia. But it is hard to know from the data available thus far, he cautions. “We’re trying to infer a lot of scientific and mechanistic information from data that doesn’t really have it to give,” he says. “We’re kind of putting things together and building a bridge across these big gaps.”
Updating vaccines
Researchers have been analysing clinical-trial data for several coronavirus vaccines, to look for clues as to whether their effectiveness fades in the face of the 501Y.V2 variant. So far, at least three vaccines — a protein vaccine made by Novavax of Gaithersburg, Maryland, a single-shot vaccine made by Johnson & Johnson of New Brunswick, New Jersey, and a vaccine made by AstraZeneca of Cambridge, UK, and the University of Oxford, UK — were less effective at protecting against mild COVID-19 in South Africa, where the 501Y.V2 variant dominates, than in countries where that variant is less common.
In the case of AstraZeneca’s vaccine, the results were particularly striking: the vaccine was only 22% effective against mild COVID-19 in a sample of 2,000 people in South Africa. However, that trial was too small and its participants too young for researchers to draw any conclusions about severe disease, says Shane Crotty, an immunologist at the La Jolla Institute for Immunology.
Some coronavirus vaccine developers are already looking at ways to develop next-generation vaccines that stimulate T cells more effectively. Antibodies detect only proteins outside cells, and many coronavirus vaccines target a protein called spike that decorates the surface of the virus. But the spike protein is “quite variable”, suggesting that it might be prone to mutating, says Karlsson, and raising the risk that emerging variants will be able to evade antibody detection.
T cells, by contrast, can target viral proteins expressed inside infected cells, and some of those proteins are very stable, she says. This raises the possibility of designing vaccines against proteins that mutate less frequently than spike, and incorporating targets from multiple proteins into one vaccine.
Biotechnology firm Gritstone Oncology of Emeryville, California, is designing an experimental vaccine that incorporates the genetic code for fragments of several coronavirus proteins known to elicit T-cell responses, as well as for the full spike protein, to ensure that antibody responses are robust. Clinical trials are due to start in the first quarter of this year.
But Gritstone president Andrew Allen hopes that current vaccines will be effective against new variants, and that his company’s vaccine will never be needed. “We developed this absolutely to prepare for bad scenarios,” he says. “We’re half hoping that everything we did was a waste of time. But it’s good to be ready.”
Nature 590, 374-375 (2021)