Identifying SARS-CoV-2 Antibodies to Detect Immunity

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As the COVID-19 pandemic continues to evolve around the globe, researchers at Massachusetts General Hospital are evaluating assays to determine the development of immunity against the SARS-CoV-2 virus.

John Iafrate, MD, professor in the Department of Pathology at Mass General, is leading serologic research studies to produce antibody tests for SARS-CoV-2. His team and others are now beginning to identify antibodies specific to the virus and the amount of antibody necessary for immunity.

"We're beginning to evaluate the use of serology, that is, we're looking for the antibodies that specifically bind to the virus," says Dr. Iafrate. "Just because you have antibodies doesn't mean you're protected. You have to know your level of antibody. That is, you must know your titer of antibody. Our challenge will be to determine what value is clinically meaningful."

SARS-CoV-2 infection occurs when the virus enters the nose and throat of a person to inject enough genetic material for particle replication. As the amount of SARS-CoV-2 increases, (i.e., viral load) it spreads to surrounding tissue and potentially further into the body infecting other organs, such as the lungs, blood vessels, brain and heart.

To identify infection, a nasal pharynx swab is used to collect and measure the virus. However, as the virus spreads to other parts of the body, antibody measurement becomes critical.

Dr. Iafrates says, "a viral-specific polymerase chain reaction (PCR) test using a nasopharyngeal swab sample is used to measure for virus. This is most useful during the acute phase of the infection. However, as the infection progresses after about four to five days after symptoms start, the immune system begins to attack the virus and the value of PCR decreases."

He adds that, "at the same time, antibody testing becomes more useful as an aid in making a definitive diagnosis of COVID-19. In that timeframe, the antibodies are just beginning to come up in the five to seven-day timeframe, post symptom onset. "

SARS-CoV-2 Antibodies are Acquired, Not Innate

The first wave immune response, called the innate immune response, is a broad non-specific antiviral defense that consists of immune cells releasing proinflammatory chemicals (cytokines). The innate immune response helps delay viral replication until an acquired immune response occurs, that is, when antibodies are made to specifically target SARS-CoV-2.

Notably, the cytokines that help start the immune response, are also known to contribute to COVID-19 symptoms (e.g., dry cough, fever, difficulty breathing). Serology is a methodology used to find viral-specific antibodies produced by the acquired immune response.

"We're looking for antibodies that recognize the virus that's floating around in your blood. These antibodies are made by immune cells (i.e., B cells), and they're critical to our ability to fight off infections," says Dr. Iafrate. "Your immune system has to be able to ramp up and make enough of this that it begins to fight off the virus. In addition to B cells, T cells are also recruited to fight the infection by specifically recognizing and attacking the individual cells that have been infected by the virus.

Immunity and Testing

The presence of antibodies does not necessarily confer protection against SARS-CoV-2. Knowing the level of virus-specific antibodies is crucial. It is also important to know if the antibody blocks infection, known as a neutralizing antibody.

"Almost certainly we'll need a certain minimal titer," says Dr. Iafrate. "Just because you have antibodies, doesn't mean it blocks the virus from entering cells. You may have an antibody that's not doing much, it's not being effective."

An antibody test that can predict whether someone's blood can prevent the virus from entering a target cell, that is, the neutralizing antibodies, will be critical. In the end such tests can inform protocols allowing people to end social distancing.

Return to Work

"If you wanted to have a return to work protocol, you will likely need to incorporate antibody testing. If you can combine that with a viral PCR test and show a robust immune response and no current infection, one can imagine a safe return to work strategy," he says.

To identify which individuals have neutralizing antibodies, Dr. Iafrate and his colleagues are validating point of care test kits.

"We're planning on mailing them to people's homes so they can do a finger stick, like a blood glucose measurement. Place a drop of blood on the device and then get a rapid answer whether there are COVID-19 antibodies or not. That can be done very fast. People want to know now, 'am I immune?' Unfortunately, this is not a controlled vaccination study, we are learning in real time and data remains sparse," he says.

Vaccine Development

Treatments to address COVID-19 are at the front line, but prevention is the ultimate safeguard. Development of vaccines is a critical step to halt replication of the virus in the body and thus inhibit the spread of the virus throughout the population. Vaccines require time for safety and efficacy studies.

"We will need to follow someone who received a vaccine for the next few years and find out how many people developed COVID-related illnesses," says Dr. Iafrates.

While there are more questions than answers right now, Dr. Iafrate is confident that the medical community will indeed develop an effective vaccine for COVID-19 in the next year. Until then, combining smart testing strategies with social distancing is our best way to lessen the impact of the virus.

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Learn more about the Department of Pathology