COVID vaccines and antibodies

Joel Eissenberg, Ph.D., Department of Biochemistry & Molecular Biology

I got the Moderna vaccine as part of the phase III clinical trial back in August and September 2020. Although it was technically a blinded trial, I knew from my symptoms after the second shot I was in the vaccine arm and not the placebo arm of the clinical trial. Nevertheless, I got myself tested for the spike antibody and confirmed it. Indeed, the levels were over eight times the minimum threshold (in arbitrary units) for a positive reaction. Unsurprisingly, a separate test for nucleocapsid antibody was negative, so I came by my spike antibody by vaccine, not prior infection.

But how does antibody titer relate to protection from a COVID-19 infection? The short answer is, it doesn’t. In vitro neutralization assays are a proxy for protection that doesn’t actually challenge a person with the virus. In these assays“ serum from an infected or vaccinated person is diluted to varying levels, then mixed with a set amount of virus. A dilution of 1:100, for instance, means that 50% of virus was still killed when 1 mL of serum was mixed with 99 mL of saline . . . The more the serum can be diluted and still kill 50% of virus, the better“

What do neutralization assays say about protection from infections?

“Natural infection with wild-type virus generally confers a titer of 1:400. With Delta, that gets bumped down to 1:100 — which is still pretty good . . . Immunity conferred by the mRNA vaccines, on the other hand, typically lands at a titer of 1:1,000 when looking at the original virus . . . viruses are really good at messing up the immune system. If you get infected, your antibody production isn’t that [streamlined]. But when you get an mRNA vaccine, you don’t have all those various parts of the immune response. . . titers for the Johnson & Johnson vaccine, at this point, don’t appear to be as high as the mRNA products. And protection was certainly diminished for the mRNA products when tested against the Delta variant. . . With Delta, mRNA vaccinated immunity falls to a titer of about 1:250.

We know that [naturally infected] people have been fairly well protected against reinfection … so that gives you an idea that maybe a titer of 1:100 gives quite good, though not perfect, protection from infection . . . So the mRNA vaccines should still give strong protection against variants.”

Neutralization assays are costly and technically challenging. Even more challenging is testing T- and B-cell responses, which are the basis for vaccine durability.

Bottom line: antibody titers bear a linear relationship to neutralization assay results and COVID protection, at least over a substantial range. For the time being, there is no agreed upon correlation scale for comparing antibody titer to neutralization assay, let alone protection from disease. For the time being, both the FDA and CDC recommend against post-vaccination serology.

What Do COVID Antibody Levels Really Mean? | MedPage Today, Kristina Fiore, Director of Enterprise & Investigative Reporting, MedPage Today October 20, 2021