Many of us are asking: Have I already been exposed to the coronavirus, and am I immune to further ... [+]
Many of us are asking: Have I already been exposed to the coronavirus, and am I immune to further infection?
A fast, easy, and sensitive new antibody test detects the specific biomarkers of long-term immune protection against SARS-CoV-2 that can answer that question.
If Covid is here for the foreseeable future—and the waves of infections from Brazil to the US and India suggest it is—then we’re going to have to find ways to keep the economy safely going despite it.
One way is to try to understand how much of the population is immune to the virus, and how long that immunity lasts. This could help us understand both whether a vaccine might be effective in the long run, and also whether solutions such as immunity passports might be a viable option.
Unfortunately, not one test can currently give us any assurance of that. We know from related coronaviruses, such as those which cause the common cold, that immunity is often very short-lived, and people can be reinfected with the same virus.
Some studies also suggest that antibodies reduce to undetectable levels within just a few months of Covid infection, spurring the widely circulated perception in recent weeks that immunity to the disease is only temporary. The antibody tests currently being used miss this vital part of the picture.
GenScript, a leading life sciences company, has a new antibody test that could raise the standard for testing and give us clearer insights on how to fight the coronavirus. Today, in the prestigious scientific journal Nature, GenScript describes early results from the test, which targets specialized virus-thwarting antibodies known as neutralizing antibodies. The results suggest we can rethink our understanding of long term immunity to Covid, and offers hope for the effectiveness of a future vaccine.
Neutralizing a pathogen
When a virus infects our body, our immune system kicks into action to combat it in a number of ways. One part of that immune response involves antibodies, the tiny proteins which recognize a virus and stick to it. But not all antibodies are made equal.
“When you have a virus, you generate all these antibodies, but only a small fraction bind to the virus in a way that prevents it from infecting a cell,” GenScript’s Eric Wang explains. “Those are the neutralizing antibodies.”
Neutralizing antibodies make up less than 1% of the total antibodies measured by current commercial tests, and Wang says they’re being missed. That means we could be underestimating just how many people are already protected against reinfection with the virus.
Neutralizing antibodies are not sufficient in all cases. But based on the body’s response to other viruses, neutralizing antibodies are a good indicator of protective immunity in most patients who have recovered from a disease.
“All the antibody tests at the moment look at total antibodies, and these can reduce significantly just a few months after a patient recovers from Covid,” says Wang. “But as long as you have a small amount of neutralizing antibody, the patient may still be immune to the virus.”
Recent studies have indicated that total antibodies, including neutralizing antibodies, do indeed reduce in both asymptomatic and symptomatic Covid survivors. A UK team suggested last week that this seemingly transient immune response, which included a reduction in neutralizing antibodies, might well be linked to the severity of the initial illness.
However, a study led by Dr. Lin-fa Wang, Director of the Duke-NUS’ Emerging Infectious Diseases program, suggests that we might rethink what this means for long-term immunity to Covid.
The research shows GenScript’s novel, specific, and more sensitive antibody test could detect significant levels of neutralizing antibodies, even in patients who show low levels of antibodies overall. This effect was confirmed across patient cohorts in two different countries: Singapore and China.
Another promising finding was gleaned from the blood serum of patients previously infected with the SARS virus of 2003, which still had detectable neutralizing antibodies 17 years after recovery, indicating the potential for long-term protection against a similar virus.
Introducing the first SARS-CoV-2 Neutralization Test
According to GenScript, the cPass test, or SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT), is safer, faster, easier, and more sensitive than traditional virus or cell-based tests with comparable specificity. It’s under review by FDA, but it already has CE-IVD clearance in Europe, and received provisional authorization for clinical use in Singapore.
David Martz, Vice President of new product development in GenScript’s Life Science Group, said, “this paper demonstrates that sVNT can detect neutralizing antibodies, better known as a biomarker of immunity, with 95-100% sensitivity and 99.93% specificity. Additionally, this new method also provides the means for standardized testing.”
So how does it work?
“It uses a different principle,” says Wang. “We don’t detect the antibody itself, but instead we check the blood for anything which blocks the binding of the virus [spike protein] to the hACE2 receptor on human cells. It’s a functional assay that specifically looks for the neutralizing antibody.”
At the moment, the company can’t say for sure that this test—even if it detects neutralizing antibodies—guarantees immunity against reinfection with Covid. That still requires further research. However, the test could offer a vital step when trying to figure out our current levels of herd immunity, for example, or whether that’s even achievable without a vaccine. When a vaccine does come along, it can also help show whether it is effective.
“We need something to test whether the people who receive vaccinations generate neutralizing antibodies,” Wang explains. “And not just any antibody. It has to be the neutralizing antibody.”
It’s neutralizing antibodies that will offer long term protection against Covid, stopping the disease before it can take hold.
The plaguing mysteries of Covid
A recent study from Spain published in the Lancet found that 5% of the population carried antibodies for Covid. The study was carried out using non-specific antibody tests, which is useful in measuring how much the virus had spread through the Spanish population. But no conclusions can be drawn on potential herd immunity among those already exposed.
“Imagine if scientists had access to the cPass test. Not only they would have been able to accurately determine the total level of neutralizing antibodies but also use this test to assess herd immunity,” added Martz. “We are very excited to see how this will shed new light on the current plaguing mysteries of Covid.”
Covid is still an enigma in many ways, and it is still unclear how long immunity to the virus will last. However, neutralizing antibodies are a pretty good indicator of immunity, and improved antibody tests provide us with a far more detailed understanding of the effects the virus is having on the population as a whole, helping us in the continued fight against the pandemic.
Follow me on Twitter at @johncumbers and @synbiobeta. Subscribe to my weekly newsletters in synthetic biology. Thank you to Peter Bickerton for additional research and reporting in this article. I’m the founder of SynBioBeta, and some of the companies that I write about—including GenScript—are sponsors of the SynBioBeta conference and weekly digest. Here’s the full list of SynBioBeta sponsors.
