SARS-CoV-2 variants: Impact on vaccines and laboratory testing

SARS-CoV-2 variants have been with us since the dawn of the pandemic, but only recently has their impact on disease and immunity been broadly recognized. Variants of concern (VOC), including Delta and Omicron, are particularly troubling as they harbor one or more characteristics such as increased infectiousness or resistance to neutralizing antibodies that can facilitate transmission. Variants of interest (VOI) display concerning mutations that require close monitoring. Genetic diversity enables the virus to adapt in ways that can impact immunity from vaccination or recovered infection, as well as some diagnostic testing.

In this free SelectScience^® webinar, now available on demand, Dr. Katherine Soreng, Global Director of Clinical Education for Laboratory Diagnostics, Siemens Healthineers, discusses viral genetic evolution and the impact of mutations, the critical role of monitoring for variants with easy-to-use RT-PCR-based molecular testing, and more.

Register now to watch the webinar on demand, and read on for highlights from the Q&A discussion:

Do you foresee the continual use of vaccination in future, including for immunosuppressed patients? And do you see a mandatory antibody test being required before the booster?

KS: At the start of the pandemic, we were all anxious to get a vaccine to market as soon as possible. Now, no steps were skipped, all the safety work was done. But one thing we did was to shorten the time between doses when we found out that one dose of most vaccines was not going to be sufficient to induce a significant level of neutralizing antibody in a high percentage of people.

We found that we had to do two doses and didn't want to wait many weeks or months in between those two doses, even though we know from other data that it's probably better, in terms of the overall immune response, to have a longer interval between doses. So, we did for example, three weeks with the Pfizer and four weeks with the Moderna, and we saw really good efficacy with that.

But then we started seeing these variants, which reduce the efficacy of the vaccines, and we saw declining immunity. Now, what we need to find out is whether a third boost given to a healthy individual 6 months later has some greater durability in the immunity than we’re seeing with the short interval in just the six-month follow-up. We're looking to see if we need to keep getting boosted every year, maybe three will be enough for most people.

It's a different story in immunosuppressed people because many do respond much more poorly, and they don't make a lot of antibodies to begin with. The only way you can really know that is to do quantitative or semiquantitative testing. I do think that antibody testing, at least in that subset of people, may end up being something that's recommended. It's not currently, but it may be because it makes a lot of sense. You don't want to keep going in for a boost every three months if it’s not necessary. So, I do think that antibody testing will play a significant role. I don't know if it'd be mandated, we have the problems with lack of standardization.

Taking into account the quick mutability of the virus, would it be better to react on new variants with more classic vaccines rather than RNA-based?

KS: I'm an immunologist by training, so traditional vaccine approaches are near and dear to my heart. But many other scientists and I, have been incredibly impressed with how well those mRNA vaccines have worked. An advantage to the mRNA vaccines is they're easy to alter, relative to some of the more standard traditional approaches, easy to alter in the face of variants. This is because you can just change the sequence in the mRNA vaccine itself, which is something that we directly synthesize. So, I would say that I know people are more comfortable with traditional vaccine approaches but don't be scared of the mRNA or even the adenoviral approaches, because we are seeing, in many cases, really good data out of that.

Do you think an antibody threshold associated with protection will be recommended?

KS: Several leading organizations, including the centers for disease control, are actively investigating a threshold. Remember that there are all these different antibody assays that are designed differently, and these haven’t been standardized. For example, we have standardized hepatitis B surface antigen antibodies amongst manufacturers, so there's a quantitative international standard. You can say: "With that vaccine, yes, we're looking typically for 10 milli-IUs per mil." We are not there yet with the antibody tests for SARS-CoV-2, although maybe eventually we will get there.

It may be that thresholds become assay specific or maybe we'll be able to use these WHO standards and the binding antibody units and the conversion factors to allow a common threshold to be identified. Do I think that there will be a threshold identified? I do. However, a threshold is not 100%. We do not get sterilizing immunity really with any vaccine, and certainly not with the SARS-CoV-2 vaccines.

So, even if you have, for example, 1,000 binding antibody units, and that was identified as protective, there is still the potential for a small set of people to get infected and maybe even become sick. Remember, those antibody levels are declining in most people over time. We'll see what happens with the boost, but they may still continue to decline. We don't know the role of the memory B cells in rapidly reproducing that antibody completely yet.

So, it's hard to say when we'll get there. But I think that, at some point, we'll at least propose a threshold that may be useful for testing.

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