The Science of COVID-19 Vaccines and Antibodies

What Are Vaccines?

A vaccine is a substance that teaches your body to recognize a foreign invader, such as a virus, sound an alarm to activate your immune system, and instruct your fighter cells and proteins to go to work to fight the virus. The goal of a vaccine is to eliminate or control the virus in your body, which could prevent infection, or control an infection from developing into disease. The vaccine causes the immune system to respond by looking as much like the invading virus as possible without causing disease itself.

Vaccines have been used for decades around the world. While smallpox is the only infectious disease to date that has been eliminated globally by vaccination, vaccines have reduced the burden of many other infectious diseases such as polio, measles, mumps, and pertussis. Most recently, vaccines for the prevention of human papillomavirus (HPV), pneumonia, and shingles have been developed.  

What Are Monoclonal Antibodies?

An antibody is a Y-shaped protein produced by B cells, which are part of the immune system. There are several different kinds of antibodies, and typically vaccines are designed to produce the antibodies that recognize and “tag” viruses as foreign invaders by binding to unique parts of a virus.

Antibodies that bind to the surface of a virus and block entry into a person’s cells can actually prevent infection or disease: this is called neutralization. These antibodies, which occur naturally in some people after vaccination or infection, can be copied in the lab and then given to people as a prevention option or treatment. The term “monoclonal” refers to these laboratory-made antibodies.

The development of monoclonal antibodies for prevention of COVID-19 is important for a number of reasons, including:

1. Monoclonal antibodies may be able to serve as another prevention option until a vaccine is available.
2. Monoclonal antibodies may be able to provide immediate protection or treatment for those who are exposed and not yet vaccinated.
3. Monoclonal antibodies may be required for people who cannot develop or maintain an adequate immune response after vaccination, such as older adults.

How Are Antibodies Different From Vaccines?

In traditional research, people get a vaccine and scientists wait to see if their bodies will respond to the vaccine by making antibodies against the virus. In antibody studies, we skip that step and give people the antibodies directly. We do this using intravenous infusions, commonly known as “getting an IV,” with shots into the skin or infusions under the skin. Another difference is that antibodies produced naturally by your body in response to a vaccine can last for a long time, but these laboratory-made antibodies usually only last for a few months, thus requiring people to get multiple infusions or injections on a regular schedule.

Where Is the Latest Information on SARS-CoV-2 and COVID-19?

What we know about the virus, SARS-CoV-2, and the disease, COVID-19, is constantly changing. To stay up to date on the most current information, we recommend that you visit the following websites for reliable and accurate information:

• US Epidemic
• Racial and Ethnic Disparities with COVID-19 in the US
• Global Epidemic

Information about how the epidemic is impacting the world (mathematical modeling):

• Johns Hopkins University
• IHME

Vaccine-Induced Seropositivity (VISP)

What Is VISP?

Antibodies help prevent infection. Most vaccines stimulate the body to make antibodies. If you get a SARS-CoV-2 vaccine, your body will likely develop antibodies to the virus. Because of this, some antibody-based tests for SARS-CoV-2 infection may return a positive result even if you are not, or were not previously, infected with SARS-CoV-2. This is called a vaccine-induced seropositivity (VISP) test result.

Two Kinds of Tests Are Available for SARS-CoV-2

• A viral test tells you if you have a current SARS-CoV-2 infection. This test detects the presence of the actual virus in your body. Some of these tests are referred to as PCR tests. A nasal swab or saliva sample is usually needed for this test.
• An antibody test tells you if you had a previous infection. A sample of blood is needed to determine if your body has developed antibodies to SARS-CoV-2.

Right now, VISP shouldn’t be a problem because the antibody tests that are widely used (either the Abbott or Roche antibody tests) do not detect the type of antibody produced by the current vaccines being developed. Instead, they pick up on a different antibody produced by a natural infection with SARS-CoV-2. However, this could change in the future as new antibody tests are developed.

Vaccine Antibodies vs. SARS-CoV-2 Infection Antibodies

Your body will make different antibodies in response to SARS-CoV-2 infection than in response to vaccination.

One of these antibodies is called a “spike antibody,” meaning that the antibody is directed at the spikes that surround the virus’s outer shell. The antibody attaches itself to the spikes on the virus in order to prevent the virus from attaching to your body’s healthy cells and causing infection. These are the types of antibodies that vaccines aim to teach your body to make in order to protect against infection.  

Natural infection with SARS-CoV-2 will produce different antibodies. These antibodies can bind to not just the spike, but also to other viral proteins such as the nucleocapsid. Current vaccines in development do not lead to antibodies against the nucleocapsid protein.

The Abbott and Roche antibody tests currently in use will only detect the second type of antibody that is produced by a natural infection with SARS-CoV-2. As time goes on and more vaccine candidates are tested, however, new antibody tests might be developed that also detect antibodies that binds to the virus’s spikes. If this happens, it means you could get a positive antibody test result, even if you have never been infected with SARS-CoV-2. Health care providers may not interpret your test results correctly as an immune response to a vaccine; they may incorrectly see it as an indication of prior infection with SARS-CoV-2. Once an effective vaccine is found and widely administered to the public, testing technology will need to clearly distinguish between vaccine responses and infection.

What Do I Do With This Information?

We have a few recommendations for anyone receiving a SARS-CoV-2 study vaccine:

1. Be sure to ask for documentation from your vaccine study team that explains your participation in the study. It should include information about the SARS-CoV-2 “spike” vaccine, meaning that you may produce a spike antibody response.
2. If you are asked to take a SARS-CoV-2 antibody test (for example, as a condition of returning to work), be sure to specify that you need to have a “nucleocapsid” test done, and do not take any type of antibody test that might only be looking for spike antibodies.
3. You can avoid this situation if you can get access to SARS-CoV-2 viral testing (such as PCR), which detects the presence of the actual virus in your body. If possible, ask for this type of test and use the documentation of your vaccine study participation as your justification.
4. We do not know if the study vaccine will lead to antibodies that can protect you from infection. We do not yet know if a positive antibody test means that you are less likely to get a SARS-CoV-2 infection or COVID-19 illness.