Measuring COVID-19 Vaccine Immune Response With VaxEffect

A new vaccination immune response monitoring platform is going beyond a simple “Yes/No” and providing clinicians and patients with more quantitative data regarding immune response to COVID-19 vaccination. The test could be especially beneficial for immunocompromised patients by informing timing for boosters down the road.

VaxEffect, created by FlowMetric Life Sciences, Inc., just recently launched. Renold Capocasale, CEO and founder of FlowMetric, and Grant Morgan, PhD, PMP, executive vice president for FlowMetric and general manager of VaxEffect, spoke this week on the platform, its clinical application, and future plans for immune response tests for other vaccines beyond COVID-19.

Transcript has been edited for clarity and length.

Q: What is the background of FlowMetric?

Renold Capocasale: FlowMetric Life Sciences was created over a decade ago as a contract research organization (CRO) dedicated to advancing pharmaceutical and biotech drug development initiatives. We specialize in cellular analysis as it relates to interrogating the immune system to address safety, efficacy, and potency of new drugs coming to market. We are divided—or broken up into—2 companies, so our CRO division, which has pharmaceutical and biotech clients, and, more recently, our diagnostic division, which is where we develop LTDs to address various test needs and VaxEffect falls under that division.

Q: What was the inspiration behind VaxEffect?

Capocasale: VaxEffect as a platform really was inspired quite some time ago when I was a researcher at [Johnson & Johnson] in the lab. My first son was born and, of course, trying to be very responsive for all of the background that I had in immunology was certainly very keen on following his vaccination schedules. I remembered quite distinctly asking pediatricians at every vaccination meeting that we had if it would be okay if I could get titers for my son, and I always posed the question, ‘Well, how do we know actually that he's generated a good immune response?’ And literally, pediatricians kind of chuckled and said to me, ‘Well, we don't really do that.’ So that was the really the genesis of the idea back when I was a bench scientist, and I took that along. When FlowMetric Life Sciences launched its diagnostic division back in 2015, we were certainly motivated to come back to that question. Certainly, at this point, the perfect storm of COVID-19 appearing on the scene made it obvious which vaccination we should begin with in terms of developing specifically a test around looking and measuring that specific immune response to a vaccine. That was the genesis of COVID-19 VaxEffect.

Q: What is the science behind VaxEffect? How does it work?

Grant Morgan, PhD, PMP: The science [is] based on flow cytometry, where we're able to actually detect levels of antibodies specifically in the blood of the patient that provides the sample. It detects a quantitative level of those antibodies, and then provides a very easy-to-understand output report that shows whether you've responded to the vaccine or have been previously exposed to the virus, and also how much of a response you generated as measuring quantitatively the level of antibodies you have in your system.

Unlike other serology tests available today, the VaxEffect test is actually built on multiplex flow cytometry and what that enables us to do is to detect 2 proteins associated with the COVID-19 virus. The first protein is called the nucleocapsid protein and this is actually found hidden inside the virus. You are only exposed to that protein if you've been previously infected by the virus. You'll generate antibodies to that, and that's able to be detected by our tests.

The second protein that the test is able to identify is the RBD protein that's on the spike part of the virus. This is actually what's used in all the vaccines that are given to everybody, and so we are able to uniquely identify over a wide quantitative range the level of antibodies you've generated to that vaccine based on the immune response to the RBD spike protein.

One of the unique things about the VaxEffect vaccine immune response tests is that, unlike other tests, it's actually able to offer 4 unique answers or responses to questions that you may have. The first one is: Did I actually generate an immune response? It's a quantitative assessment, yes/no, to generating immune response to the vaccine you received.

The second one is, because of the uniqueness of the platform we use in flow cytometry, you're able to quantify the amount of vaccine immune response that you've generated over a very wide dynamic range, and this is called the VaxEffect Score. This will not only tell you how well you've generated an immune response, but you will be able to actually see where your immune response level is in comparison to other people who've taken the test.

The third component is that you can actually track over time that immune response. We envision [a scenario] where a patient would have a VaxEffect test to see what their immune response was like to the vaccine they received, and then have repeat tests every 3 months [or] 6 months to see whether they are maintaining that specific immune response to the vaccine they received.

The last component of this is whether you have a prior exposure to the virus. Forty percent of people who were exposed to the virus did not know they had generated or been exposed to the virus, and therefore generate an immune response. We're able to actually uniquely identify those individuals who have been exposed to the virus. With this test what we think we have is something where you can uniquely quantify and track your immune response to the vaccine you received or to the COVID-19 virus that you were previously exposed to.

Q: Who is the target user for VaxEffect?

Morgan: We believe the primary user for the VaxEffect immune response test actually will be the physician's office. We believe that doctors will be really interested in utilizing the test to really understand their patient's immune response to the vaccine or if they've been previously exposed to the virus. What we've heard is that, especially in immunocompromised patients, doctors are unable to provide a real definitive answer as to whether the patient [has] actually created immune response to the vaccines they've received. This is tremendously important when patients are thinking about returning to their everyday lives, returning to interacting with their families, going on vacation.

For most of us, we don't even think about it now. We think we've been vaccinated, and we just assume we’ve had a good immune response. For immunocompromised patients, it's a different story. They really don't know if they've created that robust immune response, and the doctors are unable to provide the information. We think this test, for a healthcare provider, will be able to turn to that patient and say, ‘You know what, I can actually now give you a simple blood test and I can tell you the response you've made.’ And because it's extremely quantitative over a very wide dynamic range, that doctor will be able to say to the patient whether they've even generated a weak immune response, which may indicate that they could potentially get a booster shot, which would increase their antibody levels, and then make them feel more comfortable about returning to the world and environment than they used to.

Q: Could VaxEffect potentially help in identifying a time frame for COVID-19 booster shots?

Morgan: One of the aspects of the test that's really important is that we can do repeat testing. This will actually be timed very well with a lot of talking now about getting booster shots, either of the same vaccine you've received previously or potentially a different vaccine to see if that generates an additional immune response. What we think we'll be able to do is track over time the immune response to the vaccine and then provide that additional information to the health care provider as to when might be the right and optimum time to provide that booster to the patient.

Q: If a person registers as a low responder, what does that mean in practice?

Morgan: It's actually very interesting. For a low responder, there's a level of uncertainty as to whether there is a protective level of immune response against an exposure down the road to the virus. Right now, in the scientific community, we do not know what the correlate of protection is so what is the amount of antibodies you need to generate that protects you from further exposure to the virus? So that is not known yet, but there's a lot of research going on to understand what that correlate of protection is. The antibody test that we have, the VaxEffect immune response test, because it generates a quantitative response, we should be able to, in working with other health care providers, actually correlate the level of protection a person has and whether that should afford them protection to further exposure to the virus.

That’s something we think in the future, as more and more data [are] gathered, we will be able to offer to doctors and their patients as to whether—even if they have a weak immune response—is it sufficient to provide at least some partial protection to future exposure?

Q: Recent studies have sought to examine how immunocompromised patients, including patients with cancer, respond to the vaccine. How could VaxEffect help?

Morgan: What we're seeing with immunocompromised people, including people who have suffered from various different types of cancer, is that the immune response to the vaccine they receive is very varied. Some patients actually generate strong immune responses and, therefore, could be considered to be protected from the virus in going forward in their everyday lives.

But what they are seeing in both oncology specialties, but also for organ transplantation, diabetes, geriatric specialties, [is] that people have a reduced response to the vaccine they receive. And with regular serology tests not based on our platform of flow cytometry, they are actually getting results that say they are not generating any kind of immune response. But because the flow cytometry platform that we utilize for the VaxEffect test is so sensitive, we are actually able to identify a positive but weak immune response to the vaccine they received, which means there is a potential for a booster shot to actually increase that initial immune response that they generated.

VaxEffect is different to other tests on the market, specifically serology tests, in that a majority of them are over a very small dynamic range, which means that they can only give you really a qualitative result of ‘Yes, you've been infected or vaccinated and created an immune response,’ or ‘No, you haven't.’ The VaxEffect test, built with different technology on flow cytometry, is able to actually detect not only if were you infected with the COVID-19 virus or created an immune response to the vaccine, but also the level of immune response that you were able to generate in response to either prior infection or to the vaccine.

Q: What is the status of VaxEffect?

Capocasale: The status of VaxEffect is that we just recently launched, and we are targeting VaxEffect to health care professionals in support of their patient needs addressing basic fundamental questions around how effective was the vaccination that they received against COVID-19. To date, we've tested over 1000 individuals either looking at their response to natural infection or their immune response to whatever vaccination they received for COVID-19.

Q: What is the key takeaway for clinicians?

Morgan: We believe the key takeaway for clinicians is an additional test, something that has never been used before or been available before, for doctors to inform their patients as to how well they've responded to the vaccine they received. So not just the simple, yes/no qualitative response to the vaccine we receive, but actually be able to inform their patients that they generated an immune response, which is similar or comparable to what others who have taken the test have generated. The doctor will also be able to offer a service where they can track that immune response over time and, therefore, make informed decisions about whether a patient would need a booster shot or should take extra precautions if their immune response was below what people believe is enough of an immune response for normal return back to everyday life.

Q: Is VaxEffect only for COVID-19?

Capocasale: VaxEffect is a platform that will have life beyond just COVID-19 vaccination immune response monitoring. It is a platform that will allow us to use the same technology and science to support basically any vaccine regimen that you receive. We anticipate, later this year, launching VaxEffect specifically for other vaccines such as Gardasil or Shingrix. We are excited at the prospect of patients having a much easier ability to monitor over time their vaccine immune response.

Quite simply, we believe the most important takeaway for clinicians for the VaxEffect platform is the alignment of unmet needs for the patient and their health care provider. We think it's really important for patients who have underlying conditions that may cause them extra risk for actually generating an immune response to have an easy, accessible, and highly communicative approach to their immune response to the vaccine.

For us, COVID-19 has been, obviously, an anxiety producing event for many people. To have a patient who doesn't really know more than yes/no where they stand, immunologically speaking, in response to a vaccination we think is important. It's peace of mind for both the physician and their patient, and it's actionable because we can monitor over time with easy-to-read data that is addressable by the physician to their patient. All of us have elderly parents who have received the vaccine. Wouldn’t it be great if you could show them, in quite easy terms, that they have generated an immune response [and] that they are protected? We all know individuals who are undergoing cancer therapeutic regimens that create immunodeficiency. For them, it's not just yes/no. For them, it's nice to see that they actually have generated some response. It brings hope.