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COVID-19 Antibody Immunity Test

Jul 27, 2022

The Attomarker  Antibody Immunity Test measures antibodies in the blood to the SARS-CoV-2 coronavirus causing COVID-19. The total IgG response is measured to three antigens on the surface of the virus: Nucleocapsid (N), Spike (S) (and now Omicron Spike) and Receptor Binding Domain (RBD). RBD is the region of the spike protein that docks with the ACE2 receptor to enter our cells and indicates neutralising antibodies. 

Natural Antibodies

A patient response to the SARS-CoV-2 infection produces all three types of antibodies and to all three proteins: N, S and RBD Triple Positive ,Figure 1, and we can see the production of antibodies at14 days after symptoms for patients in a hospital recovery trial at St Thomas’. 

Figure 1 Triple Positive Response N+D+RBD for a patient recovering from SARS-COV-2 infection. CRP levels also remain elevated above the normal range of 20 mg/L

Vaccine Antibodies

The Antibody Immunity Test is also sensitive to antibodies produced by the vaccine characterised by an S and RBD response and not N, such as for the Pfizer vaccine Figure 1. The Test will tell you if the levels of antibodies are above pre-pandemic levels. 

Figure 2 Pfizer Vaccine Response after 2 inoculations showing strong S positive and RBD positive

Immunity and Antibody Lifetime

Antibody levels imply a positive, adaptive immune response which includes the production of antibodies and the T and B cell response. The concentrations of antibodies fall in time, maybe below pre-pandemic levels but immunity may still continue through the T cells and B cells, especially the B Cell “memory” response. All immunity will also fade in time and vaccine boosters have been scheduled by many authorities worldwide as a consequence . 

COVID – Secure Environments and Vaccine Efficacy

No environment can be made completely COVID secure by gatekeeper testing. A gatekeeper test such as PCR which is 80% sensitive or an LFT antigen test which is 75% sensitive in the hands of a healthcare professional and 56% when used at home. At the moment it is estimated that up to 200,000 people a day in the UK are contracting COVID,  but prevalence varies locally. About 1 in 10 people who get COVID, however badly, get long COVID

The vaccines provide significant but not complete protection against infection and illness. Efficacy is well-documented:

  • 25% of people with the Oxford AstraZeneca vaccine have no antibodies;
  • 5% of people with the Pfizer vaccine have no antibodies
  • 5% of people with the Moderna vaccine have no antibodies

You need to know if your vaccine has produced antibodies if:

  • You are a healthcare worker
  • You have a vulnerable immune system or at risk medically
  • You are visiting an elderly relative in a care home
  • You meet many people at work -occupational health
  • You are planning to travel on vacation in the UK or abroad

The vaccine may not protect you against all variants of the coronavirus.

Science Notes: COVID-19 Antibody Immunity Test

Virus Surface Antigens

The Attomarker Antibody Immunity Test uses the same markers as recommended by PHE for Vaccine Surveillance and in detailed studies on the persistence of immunity following COVID19 infection (1). The spike protein is targeted by all vaccines as responsible for the docking between the virus and the surface of our cells at the ACE2 receptor. RBD antibodies are thought to be neutralising and this RBD region is specifically targeted by the vaccines (2). 

Pre-pandemic Thresholds – Sensitivity and Specificity

The Antibody Test performance has been evaluated against 400 patients at St Thomas’ hospital and 400 patient commercial sera to derive the pre-pandemic thresholds for each of the three antigens which are then combined as a Boolean descriptor as N or S or RBD positive to give and antibody positive patients. The thresholds for immunity in other studies on protection in 18 vaccines (3) is 1 mg/L, consistent with the pre-pandemic thresholds observed in clinical trials.

The sensitivity of the Triple Antibody Tests is 96% (93% – 100%) and the specificity is 95% (92% – 99%) has been validated in a hospital setting for patients admitted with COVID19 and on collections of commercial samples. The Antibody Test has passed its CE marking validation. 

Accuracy of Virus Testing and Antibody Testing in COVID Secure Environments

The Antibody Test is more accurate than the test for the virus itself and is sensitive to viral infections 14 days after the onset of symptoms in hospital admissions. Together vaccine antibodies and antigen testing provide a measure of a COVID secure environment: antigen testing – who has the virus; antibody test – who has vaccine antibodies. For comparison: 

  • Antigens lateral flow tests are only 75% accurate when used by a healthcare professional; 56% effective when used by a member of the public (4).
  • PCR tests are 80% accurate for any one test (5); when used in a sequence of 2 tests 5 days apart they are 95% accurate.

Natural Antibodies 

Natural antibodies are produced during the infection and can be raised to N, S and RBD. The antibodies are part of an adaptive response, which includes CD4+ T cells and CD8+T cells. All parts of the immune response have a life-time between 3 and 6 months (1) hence the need for a vaccine booster. The natural antibodies and adaptive immune response provide protection against re-infections. In a study with healthcare workers in the first wave (6) 90% of recovered patients have detectable antibodies (7) and 90% non-reinfection (8). Similarly, re-infection in the SIREN study (9) 95% protection against COVID-19 symptoms and about 75% protection against being infected (10).

Vaccine Efficacy

Pfizer – 92% effective and reducing cases

  • Israel study with 596,618 participants in mass vaccination setting (11): 92% reduction in documented infection after the second dose; 87% reduction hospitalisation after the second dose; 92% reduction in severe disease after second dose.
  • Potentially 8% will not show an antibody response.

Oxford-AstraZeneca – 69% – 74% (12)

  • These are the figures from the latest ‘real-world’ setting released by AstraZeneca.
  • Potentially 31% of people will not show an antibody response. 

Moderna 

This the latest vaccine to be released in the UK and it has shown 95.2% efficacy (95% confidence limits are between 91.2 % to 97.4 %) (13)

  • Potentially 4.8% of people will not show an antibody response. 

Vaccine Antibodies and Vaccine Surveillance

The vaccines trigger an immune response to the spike protein, part of which is the RBD. The antibodies from the Moderna antibody show persistence at 6 months after the second dose (14). Similarly, T cell and antibodies have been observed from the T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial (15).

According to PHE there is currently no agreed correlate of protection with antibody levels (16) although they continue to use N and S antibody markers and seroprevalence in vaccine surveillance and it is the primary endpoint of the care home surveillance VIVALDI study (17). A recent study, yet to be peer reviewed, (18) found 50% protective neutralisation level was estimated to be approximately 20% of the average convalescent level (95% CI = 14-28%). The estimated neutralisation level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level (CI = 0.7-13%, p = 0.0004). 

But PHE are carrying out antibody test (19) and are engaged in the surveillance COVID-19 Vaccine Surveillance Strategy (16) to assess vaccine efficacy. The Vaccine Surveillance strategy is proposing the differential response for N and S to distinguish between natural infection antibodies and vaccine antibodies and they are using commercially available platforms: Abbott assay targeting N protein (SARS-CoV-2 IgG chemiluminescent microparticle immunoassay (CMIA)) and the Euroimmun assay targeting the S protein (Anti-SARS-CoV-2 ELISA IgG).

The case for antibody levels being a correlate for protection is well established in 18 other vaccines (3) and evidence is continuing to grow for the COVID19 vaccines (20) and in Government trails (21). Some authors present stronger cases: “Antibodies are the only component of immune memory that can provide truly sterilizing immunity.” Published in Science in February 2021 (1). 

The Antibody Test has a signature for vaccine antibodies S and RBD responses which are not observed in pre-pandemic samples. The pre-pandemic threshold is consistent with levels reported from 18 other vaccines (3). 

Long COVID

COVID-19 is for most recovery is complete: for some long COVID and in a survey conducted by ONS (22) around 1 in 10 respondents reported symptoms for 12 weeks or longer.

References

  1. Dan JM, et al. (2021) Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science 371(6529):eabf4063.
  2. Dai L & Gao GF (2021) Viral targets for vaccines against COVID-19. Nature Reviews Immunology 21(2):73-82.
  3. Plotkin SA (2010) Correlates of protection induced by vaccination. Clin Vaccine Immunol 17(7):1055-1065.
  4. Mahase E (2020) Covid-19: Innova lateral flow test is not fit for “test and release” strategy, say experts. BMJ (Clinical research ed.) 371:m4469.
  5. Zhang Z, et al. (2021) Insight into the practical performance of RT-PCR testing for SARS-CoV-2 using serological data: a cohort study. The Lancet Microbe 2(2):e79-e87.
  6. Reynolds CJ, et al. (2020) Healthcare workers with mild / asymptomatic SARS-CoV-2 infection show T cell responses and neutralising antibodies after the first wave. medRxiv:2020.2010.2013.20211763.
  7. Gudbjartsson DF, et al. (2020) Humoral Immune Response to SARS-CoV-2 in Iceland. New England Journal of Medicine 383(18):1724-1734.
  8. Ali AM, Ali KM, Fatah MH, Tawfeeq HM, & Rostam HM (2020) SARS-CoV-2 Reinfection in Patients Negative for Immunoglobulin G Following Recovery from COVID-19 medRxiv:2020.2011.2020.20234385.
  9. Hall V, et al. (2021) Do antibody positive healthcare workers have lower SARS-CoV-2 infection rates than antibody negative healthcare workers? Large multi-centre prospective cohort study (the SIREN study), England: June to November 2020. medRxiv:2021.2001.2013.21249642.
  10. Lumley SF, et al. (2020) Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers. New England Journal of Medicine 384(6):533-540.
  11. Dagan N, et al. (2021) BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. New England Journal of Medicine 384(15):1412-1423.
  12. SMallapaty SaCE (2021) What scientists do and don’t know about the Oxford-AstraZeneca COVID vaccine. Nature 592:15-17.
  13. Baden LR, et al. (2021) Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. The New England Journal of Medicine 384(5):403-416.
  14. Doria-Rose N, et al. (2021) Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19. New England Journal of Medicine.
  15. Ewer KJ, et al. (2021) T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nature Medicine 27(2):270-278.
  16. PHE (2021) COVID-19 vaccine surveillance strategy.
  17. Shallcross L (2021) COVID-19 in care homes (VIVALDI).
  18. Khoury DS, et al. (2021) What level of neutralising antibody protects from COVID-19? medRxiv:2021.2003.2009.21252641.
  19. PHE (2021) PHE monitoring of the early impact and effectiveness of COVID-19 vaccination in England.
  20. Earle KA, et al. (2021) Evidence for antibody as a protective correlate for COVID-19 vaccines. medRxiv:2021.2003.2017.20200246.
  21. Hall VJ, Foulkes S. et al (2021) Effectiveness of BNT162b2 mRNA Vaccine Against Infection and COVID-19 Vaccine Coverage in Healthcare Workers in England, Multicentre Prospective Cohort Study (the SIREN Study). in Lancet.
  22. Statistics OoN (2021) The prevalence of long COVID symptoms and COVID-19 complications.

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