Testing for antibodies after a COVID-19 vaccine
COVID-19 antibody testing has provided important information to those who have not been able to test for COVID-19 while unwell or tested with PCR too late or early. It has helped people confirm that the illness they experienced was indeed COVID-19. It also has limitations as some people do not develop IgG antibodies after having COVID-19.
Now, COVID-19 antibody testing is being used as a tool to check whether a COVID-19 vaccine has worked to trigger a sufficient immune response. A new test has become available that not only gives a positive or negative result but also provides a quantitative result, ie. it tells you how many antibodies you have. This test has been referred to as the COVID-19 “vaccine antibody test” in some circles.
Below we have created a patient advisory to answer the most common questions, bring together the most recent research and give you all of the information you need to make an informed choice about COVID-19 antibody testing. We hope it is of help.
Testing after contracting COVID-19
When should I test?
IgG antibodies are detectable from around 24 – 28 days post-infection.
I definitely had COVID-19 but I tested negative – how is this possible?
Not everyone who is infected with COVID-19 develops IgG antibodies. This depends on viral load (how much of the virus you were exposed to), the strength of your primary immune response and other physiological factors.
How long do antibodies stay in the system?
A study conducted in Spain of 70,000 people, found that around 14 – 15% of people shed all of their antibodies within 2 months and for others, antibody levels declined over 3 – 9 months. These findings were echoed by King’s College. Some research suggests that T cells (one of the important white blood cells of the immune system) also play an important part and T cell memory can continue after IgG antibodies are shed.
Testing after your COVID-19 vaccination
When should I test after vaccination?
To the best of our knowledge, the best time to test is 28 – 35 days after your second dose. Although you can test for antibodies after your first dose, we don’t know the degree to which a single dose provides a sufficient immune response. The UK government roll-out of the vaccine has delayed the second dose to 3 months after the first, so we understand that you might be keen to be tested between the two. Although we are happy to conduct the test for you, you should be aware that there is no clear evidence available about whether antibodies are detectable after the first dose and when.
According to reports published by AstraZeneca in the Lancet, a single dose of the vaccination resulted in a four-fold increase in antibodies to the SARS-CoV-2 virus spike protein in 95% of participants one month after injection. In all participants, a T-cell response was induced, peaking by day 14, and maintained two months after injection. Neutralising activity against SARS-CoV-2 was seen in 91% of participants one month after vaccination and in 100% of participants who received a second dose. The levels of neutralising antibodies seen in participants receiving either one or two doses were in a similar range to those seen in convalescent COVID-19 patients.
Therefore if you do decide to test after your first dose of the AstraZeneca vaccine, you should aim to test around one month after your vaccination.
We have very limited information on testing after the first dose of the Pfizer or Moderna vaccine.
What test do you use and what does the result mean?
We use the Roche quantitative antibody test for those seeking to check their post-vaccination immunity response. Neither Abbott nor the rapid cassette is advisable for this purpose.
The Roche quantitative antibody test is helpful because it not only provides a positive or negative result but also provides the number of antibodies present. This is helpful to those who also want to monitor their antibody levels over time.
The Roche test has shown 100% specificity and sensitivity after 28 days.
The limitation of testing is that the immune response to the vaccine is multifaceted and not only dependent on levels of IgG antibodies so testing for antibodies will give you a partial picture only.
Can you tell me what level of antibodies is considered a successful immunisation for each vaccine?
Both neutralizing antibodies and T memory cells play a significant role in immune response and protection post-vaccination. Measuring immunity is a complex process especially when it comes to a new infection such as SARS-COV-2. Scientists are still working to learn what constitutes an effective natural immune response therefore at present it is difficult for scientists to state definitively what a good vaccine-induced immune response would look like and it is not yet known what level, or titre, is needed for protection.
Another significant challenge is the fact that there is no standardised or pre-aligned measurement process across the globe. Each laboratory uses several types of immunoassay to measure the single aspect of the immune response. As a result of this diversity in testing methodologies being carried out in various laboratories around the world, there is currently no definitive set values for a protective immune response. In time, standardisation of assays will occur, allowing the scientific community to build a greater understanding of the immune response to the SARS-CoV-2 virus and further development of vaccines and therapeutics for COVID-19.
In summary, our test will let you know if you have COVID-19 antibodies and also tell you how many, but we do not have data yet to inform you whether your level is considered a successful immune response to the vaccine dose.
Will you know whether the present antibodies are because of a previous infection or because of my vaccination?
No, we cannot differentiate between the antibodies caused by a past COVID-19 infection and those developed as a response to your vaccination. If you have had a previous COVID-19 infection, you should let your nurse know.
I’ve had my second dose over 28 days ago but I tested negative – how is this possible?
No vaccine is 100% effective and it is possible that you did not have an immunity response to the vaccine.
The AstraZeneca vaccine is an adenoviral vector-based vaccination. Researchers have taken the genes for the covid spike proteins and modified them into a harmless virus to make the vaccination.
Once the vaccination is given, an immune response is created by the B cells locking onto the spike proteins, which then with the help of T cells will start to proliferate and pour out neutralising antibodies that target the spike protein.
Clinical trials have shown that this vaccination has an efficacy rate of an average of 70%, ranging from 62-90%. The Oxford-AstraZeneca vaccine requires two doses, given four weeks apart, to prime the immune system to fight off the coronavirus.
Pfizer and Moderna Vaccine
Pfizer-BioNTech and Moderna vaccine uses the genetic material of messenger RNA to deliver information to our cells to make spike proteins. The genetic mRNA is destroyed by the cells once the cell’s molecules have read its sequence and built a spike protein.
The T cells recognise the spike protein as a foreign agent and raise the alarm to other immune response cells such as the B cells. The B cells are then activated by helper T cells that will then produce antibodies that target the spike protein.
The Pfizer-BioNTech vaccine requires two injections, given 21 days apart. Trials of the two mRNA vaccines report efficacies above 90%.
The Moderna mRNA-1273 vaccine is given at a schedule of two doses (100 µg, 0.5 ml each) 28 days apart. If necessary, the interval between the doses may be extended to 42 days. It has overall efficacy of 90-95%.
The current government strategy is to delay the second dose of the vaccine. What do we know about antibody behaviour after only one dose of the vaccination?
The decision by the UK to extend the second dose vaccination is controversial as there is very limited data supporting this decision. This decision is taken by the UK government to protect the greatest number of at-risk people overall in the shortest possible time.
In both Pfizer-BioNTech and AstraZeneca vaccine, the trials did not compare different dose spacing or compare one with two doses.
AstraZeneca has conducted a trial in the UK and Brazil that include participants receiving different spacing between doses. The finding showed that a longer gap (two to three months) led to a greater immune response, but the overall participant numbers were small.
According to Public Health England, the Oxford-AstraZeneca vaccine provides significant protection against hospitalisation at 21 days after the dose one until 2 weeks after the second dose. This evidence suggests that the first dose might provide protection against severe COVID-19 disease. MHRA has also stated that, although optimal efficacy was achieved through two doses, both vaccines “offer considerable protection after a single dose, at least in the short term.”
A paper published in the New England Journal of Medicine stated that the efficacy of the Pfizer-BioNTech vaccine was 52.4% between the first and second dose (spaced 21 days apart).
The PHE Green Book indicates that short term protection for this vaccination starts after 10 days from the first dose. Looking at the data from day 15 to 21 on the Phase III trial, they have calculated that the efficacy against Covid-19 symptoms to be at around 89%. However, Pfizer has that there is no evidence how much the protection lasts beyond 21 days.
How long will my immunity last?
Due to the newness of the vaccination, researchers do not yet know how long protection will last. There is a possibility that the number of antibodies might decline with time but the immune system also contains special cells called memory B cells and memory T cells that might retain information about the coronavirus for years or even decades. Recent research suggests immunity may last 3 – 6 months but this is yet to be confirmed and it is too early to say for certain.
AstraZeneca PLC. COVID-19 vaccine AZD1222 showed robust immune responses in all participants in Phase I/II trial. (https://www.astrazeneca.com/media-centre/press-releases/2020/covid-19-vaccine-azd1222-showed-robust-immune-responses-in-all-participants-in-phase-i-ii-trial.html). Accessed January 2021
AstraZeneca PLC. What does immunogenicity mean in the context of COVID-19 vaccines? (https://www.astrazeneca.com/what-science-can-do/topics/disease-understanding/what-does-immunogenicity-mean-in-the-context-of-covid-19-vaccines.html). Accessed January 2021
Mahase, E. and Lacobucci, C. 2021. Covid-19 vaccination: What’s the evidence for extending the dosing interval?. Article 372:n18
Corum, J. and Zimmer, C. 2021. How the Pfizer-BioNTech Vaccine Works. (https://www.nytimes.com/interactive/2020/health/pfizer-biontech-covid-19-vaccine.html ) Accessed January 2020.
Cohn, A. and Mbaeyi, S.2020. What Clinicians Need to Know About the Pfizer-BioNTech COVID-19 Vaccine. (https://www.cdc.gov/vaccines/covid-19/downloads/pfizer-biontech-vaccine-what-Clinicians-need-to-know.pdf ). Accessed Jan 2021
Covid 19 prevention network. The Science of COVID-19 Vaccines and Monoclonal Antibodies. (https://www.coronaviruspreventionnetwork.org/coronavirus-vaccine-and-antibody-science/ ). Accessed January 2021
Centers for disease control and prevention. 2021. Interim Clinical Considerations for Use of mRNA COVID-19 Vaccines Currently Authorized in the United States. (https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html)
Macdonald, A. 2020. COVID-19 Antibody Testing: S vs. N Protein. (https://www.technologynetworks.com/diagnostics/blog/covid-19-antibody-testing-s-vs-n-protein-340327). Accessed on Jan 2021