Clinical trial data for COVID-19 vaccine candidates were released this week. Currently named BNT162b2 and mRNA-1273, these genetic vaccine use our cell’s ability to read “instructions” for building proteins to introduce a viral protein snippet into the body, and allow the immune system to respond. Here’s what you need to know about what these vaccines are, what it means, and what hurdles still may lie ahead. Roberto Cattaneo, Ph.D., is a Mayo Clinic molecular biologist who studies the measles virus. We asked him to provide context to help us interpret this news. His answers have been lightly edited.

How does BNT162b2 and mRNA-1273 work and how are they different from a standard vaccine, such as the measles?

These vaccines work on a new principle. They use messenger RNA, which tricks the cell to make one protein of the virus, the so-called spike. The human immune system recognizes this protein and makes antibodies against it.

What is a genetic vaccine? And what is messenger RNA?

A genetic vaccine is based on nucleic acids, meaning DNA or RNA. It differs from traditional vaccines that are based on live attenuated viruses, or on viral proteins. Messenger RNA is the molecule that carries the genetic information from the genome to the ribosomes. Ribosomes are the protein builders of the cell.

Why do these vaccines require two shots, weeks apart?

Live vaccines, like the measles virus vaccine, slowly replicate within a host, providing the equivalent of multiple shots. These vaccines cannot replicate, but by using two sequential shots this process is mimicked.

Roberto Cattaneo, Ph.D., is an international expert on the measles virus and is credited with discovering why it is extremely contagious (Nature, 2011).

What is the significance of the BNT162b2 vaccine reportedly causing both antibodies and T cells to be made by the host?

The immune system has two arms: humoral immunity (antibodies) and cellular immunity (T-cells). Having two armor layers for protection is better than having a single layer.

How should people interpret these interim results?

Very encouraging. It may soon be possible to effectively protect individuals from the most severe consequences of SARS-CoV-2 infection.

What kind of signals for effect or safety should the public look for as more information is released?

Several large phase III clinical trials are currently ongoing. These include both safety and efficacy analyses. Tens of thousands of individuals are “vaccinated,” but only half receives the vaccine; the other half receives a placebo. The vaccine and placebo doses are coded, so that nobody knows who is really being vaccinated and who is in the control group. Some of these “vaccinated” individuals will accidentally get infected. Once the number of infected subjects is high enough (hundreds of accidental infections), the code is broken. These numbers will then reveal whether the vaccine is safe, and how efficiently it protects against the virus. All these numbers will be available to the agencies evaluating candidate vaccines, and to the public.

Anything else important that the public should know about this vaccine trial, vaccine, or in general on this topic?

A vaccine would be great but in the meantime continue to stay alert, wear your mask, and keep a safe distance from others.

- Sara Tiner, edited to include mRNA-1273 on November 16, 2020; originally posted November 11, 2020

  • To read more about Mayo’s infectious disease research, head over to these stories.
  • To read more about Dr. Cattaneo’s work, click through to these stories.