The world has been fixated for months on novel-coronavirus PCR testing, contact tracing and vaccination.
Meanwhile, another major part of the Covid biomedical complex has received far less attention: the use of antibodies for detecting, diagnosing and treating infection with the novel coronavirus.
This is part of the biomedical gold rush: by last summer already, antibodies were on track to become the most lucrative medical product, with global revenue projected to reach nearly half a trillion dollars by 2024. Profit margins in the range of 67% aren’t uncommon.
Pharma giants such as AstraZeneca, Novartis, GlaxoSmithKline and Eli Lilly are among the companies grabbing the largest chunks of the novel-coronavirus-antibody market. And some of the most muscular government agencies, including Anthony Fauci’s US National Institute of Allergy and Infectious Diseases and the US’s Defense Advanced Research Projects Agency, are part of the action (see, for example, the second-last section of this article, on antibodies used to treat Covid).
Virtually every study and piece of marketing material related to Covid is premised on scientists having positively and correctly identified the presence of the novel coronavirus (also known as SARS-CoV-2) in the material they’re working with.
The job of that identification is usually given to antibodies that are said to bind to the novel coronavirus. The assumption is these antibodies are able to pick out the virus and only the virus from among every other organism and substance surrounding it.
Unfortunately it turns out that the antibodies rarely (if ever) do that. This is because of, among other things, inadequate verification of the antibodies’ accuracy in targeting the virus by the companies that manufacture and sell them. And there’s even less verification by government regulators.
Let’s take a 30,000-foot tour of a couple of the main features of the antibody-industry landscape, which is awash in complexity and cash.
CAN ANTIBODIES BE CREATED THAT ONLY BIND TO ONE TYPE OF VIRUS OR ANOTHER?
Antibodies are tiny, finely-tuned, parts of our immune system. One of their main functions is to seek out viruses and bacteria that may have the potential to cause disease. Antibodies bind to and neutralize these microbes so they can’t multiply and spread.
Humans and our ancestors have been making antibodies in our bodies to fend off infections for millions of years. Then a few decades ago companies got involved in the discovery and manipulation of antibodies, partnering with university labs.
There are two main categories of antibodies. One is ‘polyclonal’ antibodies. These are garden-variety antibodies that bind to a variety of different substances and/or organisms.
The other is monoclonal antibodies. As the name implies, cloning is involved in their creation. First an antibody that is specific to a particular amino-acid sequence (amino acids are the building blocks of proteins) of interest – for example, one from a protein on the surface of a virus or bacterium — is identified. Then the immune-system cell which produced that antibody is ‘cloned’ in the lab. As a result, each set of monoclonal antibodies binds to that particular amino-acid sequence.
I emailed one of the English-speaking world’s leading authorities on monoclonal antibodies, Harvard Medical School professor Clifford Saper, to get clarity on this. I asked him if it’s true that, as most in the antibody-commercializing arena claim, a monoclonal antibody can be created that’s specific for (that is, binds to) just one type of virus or just one other type of organism.
Saper replied [bolding and italics added by me for emphasis]:
No, there is no such thing as a monoclonal antibody that, because it is monoclonal, recognizes only one protein or only one virus. It will bind to any protein having the same (or a very similar) sequence.
The implication of Saper’s statement is that any attempt to use a monoclonal antibody to verify the presence of the novel coronavirus will yield a large rate of false-positive results. That is, they will indicate that the novel coronavirus is detected when in fact it hasn’t been. That’s because there’s a high probability that the monoclonal antibody is binding to something else besides the virus (this is known as ‘cross-reacting’).
And in fact, the vast majority of antibodies and monoclonal antibodies marketed as being specific for the novel coronavirus were developed years ago for detecting SARS-CoV-1. They were then simply repurposed for identifying SARS-CoV-2 — with very few if any checks for whether they also cross-react to other organisms or substances.
I sought confirmation of this repurposing from Zhen Lu. She’s the North American marketing manager for Sino Biological, a Beijing-headquartered company that develops and sells, among other things, hundreds of antibodies. Lu replied to me via email, “Yes, antibodies are repuposed [sic].”
I also checked and received confirmation from Pratiek Matkar, a senior staffer from BenchSci, an antibody-database company. And to see for myself, I logged into the BenchSci database (Matkar granted me a guest account), selected all antibodies for the novel coronavirus, and looked to see which organisms had been used in cross-reactivity tests for them. SARS-CoV-1 was the only one that came up in this check.
This all explains something I observed last week: Sino Biological had just changed the content of its home page for the section of their website on antibodies against SARS-CoV-2. The page now announces that they’ve introduced new “matched antibody pairs” that work better at finding the virus. The pair consists of a “capture antibody” and a “detection antibody.”
And they claim these pairs are more accurate at finding the novel coronavirus: that they…
have high specificity without cross-reactivity with MERS-CoV, [or with the common human coronaviruses] 229E, NL63, HKU1, [and] OC43.
The only way I can interpret that is: they know the antibodies they’ve been marketing for months as being specific for the novel coronavirus bind to other things, such as common human coronaviruses.
HOW ARE ANTIBODIES HARNESSED IN TESTS FOR THE NOVEL CORONAVIRUS?
One of the main types of tests for the virus contains antibodies that are ostensibly specific for the novel coronavirus. The way they’re designed to work is that if the virus is present in a blood sample the antibodies bind to it and, as a result, the test gives a positive signal.
The other type of test contains sequences of protein from the novel coronavirus; if antibodies to the virus are present in a blood sample, they bind to the protein sequences and produce a positive result.
The manufacturers are supposed to conduct accuracy checks of their test kits before they put them on the market. These checks largely consist of estimation of the rates of false positives and false negatives (the latter is a negative result when the antibody or protein of interest is contained in the sample being tested by the kit).
However, companies do this cursory accuracy check with only very few samples of a small number of viruses — and rarely on bacteria or any other of the millions of biological substances that can be present in the blood.
Despite this very inadequate validation and the strong incentive for the companies to make their products look good, as documented last May by David Crowe, the manufacturers often record a significant rate of false positives. The false positives are to everything from West Nile virus to various types of human coronaviruses…
The statements, views and opinions expressed in this column are solely those of the author and do not necessarily represent those of The Duran.