Antibodies assay: UCSD lab looking for clues to coronavirus immunity

Dr. Ray Suhandynata loads samples for analysis on the Diazyme DZ-Lite 3000Plus analyzer at the UC San Diego Center for Advanced Laboratory Medicine. The instrument measures concentrations of antibodies directed against the coronavirus that causes COVID-19.

A team of UC San Diego scientists is developing a COVID-19 antibody test and is hoping it will provide answers for immediate medical use against the coronavirus that causes the potentially deadly respiratory disease.

“An antibody test looks for antibodies against the virus,” said Dr. Robert Fitzgerald, a professor of pathology at UCSD and a member of its Center for Advanced Laboratory Medicine. “If you get exposed to the virus, your body responds and develops antibodies, which is the immune complex fighting the virus. The antibody test tells you that you were exposed at some point.”

The test “identifies people who can be used as serum donors. They take serum from people who have antibodies and infuse that serum back into sick patients,” he said. “The antibodies help fight the virus, mounting a robust immune response while the patient’s immunity develops.”

Fitzgerald said the human body “typically takes five to 15 days to develop these antibodies, but if you’re transfused with them, you get an immediate bolus [dose] of them. By giving the therapeutic serum early on, the hope is it’s like giving a drug to fight the disease.”

“Patients would only be given this therapy if they are acutely ill,” Fitzgerald said, which is different from a vaccine that’s “most effective when virus titer, or amount of virus in the body, is low. A vaccination works by stimulating your immune cells to develop antibodies; you get it and over the course of the next weeks develop immunity.”

Vaccines, he continued, “would be given widely, just like the flu shot or for hepatitis B. Only people who have a diagnosis of COVID-19 ... would receive antibody therapy.”

A local scientist is leading a search for antibodies in the fight to provide immunity from the COVID-19 coronavirus.

Fitzgerald said he’s looking at two antibodies: IgG, and IgM. “Ig stands for immunoglobulin, which are antibodies. There are specific cells that make these immunoglobulin. First, they make IgM, and in time, the IgM converts to IgG. The IgG typically sticks around for almost forever.”

Although scientists search for IgG antibodies for lifelong immunity, Fitzgerald emphasized the importance of testing for both IgG and IgM antibodies: “IgM says it’s a more recent infection; if you were IgM-positive but IgG-negative, that might indicate a recent infection.”

Recent infections, he continued, need to be confirmed by a polymerase chain reaction, or PCR, test. Those differ from the antibody tests in that a PCR test looks for the presence of an antigen, or active disease, and the antibody tests look for the body’s immune response.

“PCR is telling us active disease,” Fitzgerald said. “You are infected and you are infectious and need to be quarantined.”

The antibody test says “you were exposed at some point. You might still be infected, but you could also be recovered.”

UCSD’s antibody tests are more sensitive and specific than those currently offered by several doctors and clinics across the county, Fitzgerald said.

“There isn’t any good data to show that most of them work; their reliability is widely variable,” he said. “We’ve spent a lot of time here at UCSD validating the performance of this assay, or test. We had access to patient samples from PCR-confirmed positive patients and were able to look at those patients over time and see their antibody response come up. We know they’re true positive patients.”

“The antibody test will be important for determining the prevalence of a disease, because of the number of people who likely had it, were asymptomatic and recovered,” he added. “A PCR test won’t work in that case, as the virus will have cleared.”

Prevalence, Fitzgerald said, “is the number of patients with the disease [either active or at some point] divided by total population.” He said San Diego, with less than 1 percent, does not have significant prevalence, which he considers above 20 percent.

Antibody tests also can be used for other measures. “For one, it can be used to figure out if first-responder personal protective equipment is effective,” Fitzgerald said. “Were the things that you were doing protecting your workforce?”

He said UCSD is “using this assay, along with PCR, to screen our first responders in the UCSD Health Emergency Department to help ensure safe access to anyone who needs urgent care.”

Fitzgerald said there’s another use of the antibody test: After a vaccine is administered, the test “can see who’s mounted an antibody response; it tells us yes, the vaccine’s effective or no, you need a booster.”

Early development of a vaccine will use an antibody test shortly thereafter to check its efficacy.

Fitzgerald cautioned, however, that a vaccine is still “months to a year” away. ◆