Measuring the Antibody Response to SARS-CoV-2

As SARS-CoV-2 vaccines are rolled out around the globe, it is increasingly important for clinicians to be able to measure the body’s immune response over time, to understand how effective protection is and how long it lasts. Antibody tests have a vital role to play in the fight against COVID-19, helping to assert and measure the antibody response after infection or vaccination.

To learn more about the ways that antibody tests are being used in the pandemic, Technology Networks spoke to Heather-Read Harper, European Senior Manager for Immunoassay and Clinical Chemistry at Beckman Coulter. Heather also highlighted the advantages of quantitative antibody tests and discussed why detecting both IgG and IgM can be valuable.

Anna MacDonald (AM): Can you explain some of the roles that antibody tests are playing in the fight against COVID-19?

Heather Read-Harper (HRH): Antibody tests, also known as serology tests, tell us the phases of immune status of an individual and look for the presence of antibodies. There are two types of antibodies typically measured in blood: IgM antibodies, in general, are the body’s first line of defence against a virus, while IgG antibodies offer a more sustained immune response to a virus. 

Antibody tests play a critical role in understanding the level of immunity an individual has developed against the SARS-CoV-2 virus. This type of understanding can help identify those more at risk of infection and those who have been previously infected and could safely return to work or university, for example.

Wider scale testing can also provide an overview of the immunity status of the population and potentially help guide the future management of this virus.

With vaccine programs well underway, these assays have the potential to play a vital role in understanding an individual’s immune response to the vaccine over time and how long immunity might be maintained.

AM: What are the advantages of detecting each type of antibody?

HRH: In the first few days following infection only the virus can be detected. This is when it multiplies and is readily transmitted to others. At this point, molecular diagnostic PCR-based tests and antigen tests can be used to detect the virus. The individual’s immune system then starts to respond to the viral load as part of the acute phase of infection. This is when IgM antibodies are produced and increase to fight the virus and can be used to identify patients with a more recent infection. After about a week, the convalescent phase of the infection is reached and IgG is produced and increases, while IgM starts to decline. The time it takes, however, does vary from one individual to another individual’s response.

Following these principles of infection, we can utilize both IgM and IgG assays to understand the immunity status and stage of infection in an individual, although IgG is thought to provide the necessary immunity to reduce the impact of future infection.

AM: Beckman Coulter recently launched the Access SARS-CoV-2 IgG II antibody assay. Can you provide an overview of how the test works?

HRH: The Access SARS-CoV-2 IgG II assay measures IgG antibodies directed to the receptor-binding domain of the spike protein of the coronavirus in response to a previous infection. It uses immobilized virus antigens on magnetic particles to capture IgG antibodies from patient samples and reveals them using labeled anti-IgG antibodies.

The assay then provides a numerical result ranging from 2.00-450 AU/mL as well as a qualitative result for SARS-CoV-2 IgG antibodies. The test has a confirmed 99.9% specificity and 98.9% sensitivity 15-60 days post symptom onset. The Access SARS-CoV-2 IgG II assay can be used in Random Access Mode (RAM) and seamlessly integrated into existing workflows without batch processing. The assay can also be used with a variety of Beckman Coulter analyzers, including the high-throughput DxI 800 designed for large labs, the DxI 600 for mid-sized labs and the Access 2 analyzers for smaller labs and healthcare clinics.

AM: Why were IgG antibodies directed to the receptor-binding domain of the spike protein chosen as the target?

HRH: The coronavirus has four types of protein: membrane, envelope, nucleocapsid and spike. It is the spike protein that is the major surface protein of the coronavirus and mediates entry into host cells. The receptor binding domain (RBD) of the spike protein binds strongly to a receptor on respiratory cells called angiotensin-converting enzyme 2, or ACE2. ACE2 is the entry receptor of the human cell and once the viral cell membrane fuses with human cell membrane, the genome of the virus enters the human cells and begin infection.

It is believed that the IgG antibodies that bind to the RBD of the spike protein may be key to understanding the immune response to the virus and in vitro studies have shown that the existence of these antibodies may indicate neutralization of SARS-CoV-2 infection and render the virus incapable of infecting cells.

The Beckman Coulter SARS CoV-2 IgM and IgG II assays are both directed at the receptor-binding domain of the spike protein, in order to detect antibodies that are potentially protective.

AM: What are the advantages of a quantitative antibody test?

HRH: Many of the serology assays available at the start of this pandemic were qualitative in nature. This meant only a positive or negative result was generated. The results, therefore, only provided information to clinicians on whether the patient had been exposed to the virus. The result did not give a clear picture on the immune response over time.

Quantitative assays deliver a numerical value that can quantify the level of antibodies in blood. Assays such as Beckman Coulter’s SARS CoV-2 IgG II allow clinicians to monitor trends in a patient’s antibody levels by establishing a quantitative baseline and thus assess a relative change of an individual’s immune response to the virus over time.

Heather-Read Harper was speaking to Anna MacDonald, Science Writer for Technology Networks.