Feature Article: Antibody Testing After COVID-19 Vaccination

As people continue to get vaccinated, some wonder how to know if the vaccine worked. Answering this question is more complex than it may appear. So, let’s take a look.

Measuring immunity

For some pathogens, scientists have identified a “correlate of protection,” which is typically a quantity of specific antibodies above which a person is protected against an infection and below which protection is uncertain. For example, if a person has antibodies against hepatitis B surface protein of at least 10 milli-international units per milliliter of blood (10 mIU/mL), they are considered immune to hepatitis B. On the other hand, if they have less than 5 mIU/mL, they are considered susceptible to hepatitis B infection. For those with levels between 5 mIU/mL and 10 mIU/mL, their immunity is uncertain. Healthcare providers use our understanding of these measures to inform the diagnosis, treatment and prevention of hepatitis B in their patients.

Unfortunately, correlates of protection have not been identified for all pathogens, including SARS-CoV-2, the virus that causes COVID-19. Scientists are working to identify such a correlate, and early studies suggest that particular antibodies against the virus may serve this role. However, more research is needed to reproduce these findings, better understand which specific antibodies indicate protection, and determine at what antibody levels protection is likely. It’s also important to note that the immune system is remarkably compensatory, meaning there may be more than one path to protection. In the case of COVID-19, this is evidenced by some data suggesting that certain types of T cells can also affect a person’s course of infection. Whether T cells can prevent infection, or whether they just alter severity of infection, remains to be determined. With this in mind, a single correlate of protection may only tell part of the story when it comes to an individual’s immunity against COVID-19.

So, now you may be wondering, if we don’t have a correlate of protection, how do we know COVID-19 vaccines work? By comparing the infection rates of trial participants in the vaccine and placebo groups, scientists were able to determine that fewer people got infected after vaccination. This example demonstrates an important distinction between evaluating groups of people versus individuals:

• By studying groups of people, scientists can draw conclusions about the effectiveness of vaccines.
• Whereas, correlates of protection help individuals and their healthcare providers know their protection status.

Defined correlates of protection would also allow future vaccine studies to be designed differently. These correlates obviate the need for large clinical trials in people who did or didn’t receive the vaccine. For example, with a correlate of protection, scientists could vaccinate a group of individuals with a potential new vaccine and know that if their immune responses reached a certain level, the vaccine worked. Likewise, scientists may also compare the immune responses following the new vaccine with those of a group of individuals who got an existing vaccine to identify differences in their effectiveness. Efforts to identify a correlate of protection against COVID-19 are important and ongoing.

Getting an antibody test

Because we do not yet have a correlate of protection, getting an antibody test to see if the vaccine worked is not as helpful as it would appear. Additionally, all antibody tests are not created equal, so some individuals have reported negative antibody tests after being vaccinated and are concerned that the vaccine did not work. Even if the vaccine worked, a vaccinated individual may get a negative result for two reasons:

• What is measured — The current vaccines are based on the SARS-CoV-2 spike protein, so a test that measures antibodies against any other part of the virus will not detect antibodies against spike proteins. As such, this type of test would not be helpful for someone trying to figure out if the vaccine worked. On the other hand, using an antibody test that does not detect spike proteins would be helpful for diagnosing a COVID-19 infection in someone who has been vaccinated, since antibodies against another part of the virus would mean that the individual was infected. Having different types of tests is important for different situations, but if individuals or providers do not choose the correct test, it can also lead to frustration and fear.
• Accuracy of the test — In addition to choosing the correct test, individuals also need to consider the quality of the test. As the Food and Drug Administration (FDA) approves vaccines, it also reviews and approves medical tests and devices. It is important to ensure that a test has been FDA reviewed because that means the data generated during development of the test showed that it works in the way it is advertised. Two important measures include:
  • Sensitivity — Indicates how often the test correctly identifies all of those people who were infected or vaccinated.
  • Specificity — Indicates how often the test correctly identifies only those people who were infected or vaccinated, and not others who weren’t.
  False positives and false negatives can both cause issues, particularly depending on the situation. For example, if a test falsely indicates that a healthcare worker has antibodies against hepatitis B, they may not receive appropriate treatment following an accidental needlestick at work. On the other hand, if a pregnant woman gets a negative hepatitis B test, her baby may not receive the appropriate treatment to protect against hepatitis B infection immediately after birth.

Because we do not know what antibody tests mean in terms of protection and using inappropriate or low-quality tests wastes resources, antibody testing to check whether a COVID-19 vaccine worked is not recommended. Further if someone is tested, the results should be interpreted with caution.

Moving forward

As you may now realize, telling whether one’s COVID-19 vaccine worked is not as straightforward as it may seem. So, people wonder what they should do, particularly because uncertainty is uncomfortable.

1. If you have received all recommended doses of the vaccine you started and at least two weeks have passed, you are considered “fully vaccinated.” For most people, this means they either will not get infected at all or if infected, their disease will likely be less severe or of shorter duration.
2. Since no vaccine is 100% effective, you should continue to follow CDC guidance related to public health measures. Not only will this protect people who have yet to be vaccinated, it will also decrease your chance of getting infected if you’re among the small group of individuals for whom the vaccine did not work.
3. Over time, as more people become immune through vaccination or infection, the virus will be less present in our communities. This, too, will help individuals for whom the vaccine did not work. This reality is another reason why it is so important that everyone who can be vaccinated get vaccinated.

As communities reach herd immunity, even people who are not protected will be able to move about more freely and forgo some of the public health measures that we continue to practice.

Learning more

If you are interested in learning more about any of these ideas, check out these resources:

• Should I Get an Antibody Test to Know if the COVID-19 Vaccine Worked? — Watch this video in which Dr. Paul Offit discusses antibody testing.
• Correlate of protection — Watch this video to learn about studying antibody levels and reinfection in a fishing crew in an effort to identify a COVID-19 correlate of protection.
• COVID-19 antibody tests approved by the FDA
• Sensitivity and specificity of tests
• CDC guidance for fully vaccinated people

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