What is the difference between antibodies from vaccination and antibodies from having had COVID-19?

Biology/Immunity Vaccines

Q: Is there a difference between the antibodies you develop from the vaccination and the antibodies you develop from having Covid19? Is there a reason that antibody tests aren’t a good indicator of whether the vaccine was effective for you.

A: Antibodies developed from having from COVID-19 recognize different parts of the virus while antibodies from the vaccine specifically recognize the spike protein.

Some antibody tests do not test for presence of antibodies to the spike protein but rather to antibodies against a different SARS-CoV-2 protein called nucleocapsid. Universal antibody testing is not recommended after SARS-CoV-2 vaccination because the clinical trial data show that levels of antibody against the spike protein is high after vaccination in the patients tested and antibody tests are not developed to be predictive for immunity against COVID-19.

The Pfizer, Moderna, Astrazeneca, Janssen, GSK and Novavax vaccines all train the immune system to recognize the spike protein of SARS-COV-2. The spike protein is the part of the virus that it uses to get into your cells. But developing antibodies against the spike protein the vaccines stop the virus from using the spike protein to enter the cell. The antibodies bind the spike protein and then the spike protein would not be able to see anything- like a blindfold covering the eyes of the virus. Neutralizing antibodies physically stop the virus from entering a cell.

Antibody tests vary widely in the methods used, the types of antibodies they are detecting and which proteins the antibodies recognize. Some of the antibody tests look for antibodies against the spike protein but other antibody tests look for antibodies against nucleocapsid- a different SARS-CoV-2 protein. Some antibody tests can also recognize other everyday coronaviruses- they are not specific for SARS-CoV-2. The FDA has a list of tests with Emergency Use Approval that includes sensitivity, specificity, and which protein it targets (Link below).

In general, antibody testing is not recommended after vaccination because 1.) it is not needed with a healthy immune system, antibody responses in the clinical trials have been relatively universal and 2.) antibody detection tests do not predict levels of antibodies that inhibit the virus from entering a cell. To determine levels of neutralizing antibodies- the antibodies that stop the virus from entering the cell- special tests are run by laboratories that can grow viruses. In the clinical trials, scientists determined the levels of antibodies that could stop the virus from entering a cell in a culture dish. This is not a routine assay.

It is possible to test negative for antibodies after having the vaccine series if the test used was only against nucleocapsid and not against the spike protein. Also there are specialized circumstances when a health care provider may test for antibodies after vaccination or after having COVID-19. Please consult with your provider.

Use of antibody tests

List of EUA authorized antibody tests to SARS-CoV-2

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