How serology testing could impact SARS-CoV-2 vaccine delivery

Ensuring the effectiveness of COVID-19 vaccines will play a key role in promoting public health, including prioritization of the more vulnerable populations if vaccine supplies are limited, assessing sufficient and durable protection, as well as building and promoting public confidence.

In this on-demand SelectScience^® webinar, virologist Dr. Angela Rasmussen details how serology testing is necessary to understand whether vaccination results in seroconversion and a sustained response in each person, especially for high-risk/high-exposure people. She describes how clinical serology testing is relatively low cost and high throughput, with fast turnaround and broad population access, and explains why this testing will be necessary to confirm the production of neutralizing antibodies.

Read on for the highlights of the live Q&A session or register to watch the webinar at a time that suits you.

Q: Does a serological test for immunity also evaluate permission for vaccination?

AR: Some recent data has shown that people who had previously had COVID, as determined by serological testing, were essentially fully protected by a single dose of the Pfizer or Moderna mRNA vaccine. This is one example of how serology testing could be used to re-evaluate priority for vaccine doses, while allowing us to maximize our vaccine supply and still provide people with maximum protection if they are in a high-priority group.

This, and data from people who have had COVID before, suggests that natural immunity does provide some level of protection. In places where there is a serious supply shortage, we could use serological testing to prioritize people who have never been infected before and have no protection, versus people who have some partial protection. Serology testing is something that really should be implemented more, especially as we are trying to use our vaccine dose supplies as efficiently as possible.

Q: In a vaccination program for some viruses, e.g., hepatitis B, we first need to do an analysis of antibodies to the virus before giving the vaccine, to avoid giving it to any previously non-symptomatic infected individuals. Do you think this step should be applied to the coronavirus vaccine programs?

AR: That is not true for every vaccine. It is different for hepatitis B because it is a chronic infection, and that can impact vaccine efficacy. In this case, it might be useful to do serological testing before vaccinating somebody, and you should do PCR testing to make sure that a person is not actively infected when you vaccinate them. It does not matter, in this case, if you are vaccinating people who are seropositive. The only implications have to do with maximizing vaccine supplies, as I discussed before.

It is important for people to keep in mind that SARS-CoV-2 is a very different virus to something like hepatitis B, which causes chronic infection. Ultimately, we should still be vaccinating people whether they've previously had COVID or not. In the short term, while supplies are limited, we might be using serological testing to prioritize people for vaccination and not to exclude them from vaccination.

Q: What level of SARS-CoV-2 neutralizing antibody has been demonstrated to be protective against reinfection after receiving a vaccine?

AR: Unfortunately, the answer is we don't know. It does appear that neutralizing antibodies are one of the strongest correlates of protective immunity. However, no definitive correlates of protection have been established. The best we can do is say that these antibody levels are at the higher end of the spectrum compared to convalescent patients, in terms of their neutralization. We don't know the threshold at which neutralization becomes equivalent to functional immune protection.

Q: Are IgG serology assays superior to total antibody serology assays for assessing neutralization activity and for monitoring neutralization activity over time?

AR: Over time, IgG serology assays are going to be the most useful because the IgM response goes down as isotype switching occurs, but the majority of antibodies being produced are IgG. IgM can be helpful, but there have been very inconsistent results in trying to measure IgM, which is one of the reasons why looking at IgM titers or IgM to IgG ratios isn't always useful for diagnosis. Over time, IgM doesn't matter as much in terms of long-term neutralizing antibody titers and long-term immune protection.

What I'd really like to see, rather than looking at IgM, are serology assays that could either look at both IgG and IgA antibodies or distinguish between IgG and IgA antibodies. The reason for that is that IgA antibodies are thought to be very important for immune protection on mucosal surfaces, which is the primary route of transmission for SARS-CoV-2. It's thought that IgA neutralization may be more effective for neutralizing the virus in the upper airway in particular. It would be great to be looking at neutralizing IgA activity over time as well, especially in the context of vaccination, to get a better idea of how well those antibodies might be protecting against infection, as well as protecting against COVID-19 symptomatic disease.

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