How do RNA-based vaccines work

mRNA vaccines to fight the COVID-19 pandemic

What is an mRNA vaccine and how do mRNA vaccines work?

mRNA vaccines are based on messenger ribonucleic acid (mRNA) and are a novel technology that stimulates the body's own immune response. These vaccines contain information from the mRNA, including the “blueprint” or code of a specific virus trait (virus antigen). Based on the information, the body can produce this antigen itself: the mRNA transmits the information for the production of the antigen to our cell machinery, which produces proteins. Cells in our body then present the antigen on their surface and thereby trigger the desired specific immune response. When the body comes into contact with the virus, the immune system recognizes the specific antigen and can fight the virus and thus the infection quickly and in a targeted manner.

In the case of the mRNA vaccine against COVID-19, the body, and thus the immune system, recognize the virus based on the spike protein of the coronavirus that is on the virus surface. mRNA vaccines against COVID-19 are designed to provide our bodies with the code to produce a non-infectious viral spike protein. In doing so, they instruct the cell machinery to stimulate a natural immune response. This immune response is mainly achieved with the help of T cells and the production of neutralizing antibodies, with the aim of preventing SARS-CoV-2 infections and the associated disease COVID-19. If a vaccinated person later comes into contact with SARS-CoV-2, the immune system recognizes the surface structure, can fight and eliminate the virus. Neutralizing antibodies directed against SARS-CoV-2 circulate in your body and then immediately bind to the virus, "neutralize" it and prevent the virus from entering the cell. In this way you will be protected from illness. T cells help the immune system fight intracellular infections, and they can also kill the infected cells directly.

In contrast to conventional vaccines, an mRNA vaccine does not contain any viral proteins itself, but only the information our own cells need to produce a virus trait that triggers the desired immune response. The mRNA technology made it possible to develop several vaccine candidates against COVID-19.

Mode of action of mRNA-based vaccines

So the vaccine does the presentation small, harmless fragments of the COVID-19 virus for the immune cells, so that they “Learn” how to recognize and attack the virus. This enables a rapid and specific immune response upon exposure to the actual virus. This prevents its replication and spread in the human body and transmission to other people.

More information on mRNA vaccines:

How do mRNA vaccines differ from “conventional” vaccines?

How are traditional vaccines made?

Conventional vaccines usually contain weakened or inactivated pathogens or pathogen proteins (antigens) that stimulate the immune response of the body, which can react faster and more effectively if it is exposed to the infectious agent in the future.

The production of traditional viral vaccines in bioreactors is a common process, but it is lengthy and cumbersome: this process, which can take several months, involves several steps such as seed virus preparation, fermentation, harvesting and purification. In addition, dealing with large amounts of live viruses is required.

How are mRNA vaccines made?

A different approach is used with mRNA vaccines: They take advantage of the process in which the cells themselves produce proteins from the information encoded in the messenger ribonucleic acid (mRNA). This “blueprint” is translated by the body in order to synthesize specific proteins (antigens).

An mRNA vaccine consists of a strand of mRNA that codes for a disease-specific protein (antigen). In order to improve the integration of this blueprint mRNA in the body cells and to increase the vaccine stability, the mRNA is enveloped by certain fatty substances (lipids): lipopolyplexes made from lipid nanoparticles.

Once the mRNA vaccine is injected into a person, the lipid nanoparticles protect the mRNA from degradation and help the mRNA to reach the cells. In these cells, the information contained in the mRNA strand is read and the antigen protein is produced, which ultimately triggers the desired immune response.

Interest in mRNA technology as a vaccine platform has grown over the past two decades. An mRNA-based vaccine is faster to manufacture than conventional vaccines, because only the blueprint has to be produced, not the antigen itself.

RNA vaccines and conventional vaccines

The manufacturing process of RNA vaccines can speed up the response to infectious disease outbreaks. Below is how RNA vaccines differ from traditional vaccines.

Conventional vaccines

Very complex and time-consuming process

The production of conventional vaccines against viral diseases is very time-consuming and complex. The vaccines are obtained from the respective pathogens, which are grown in cell cultures or, in the case of flu viruses, in hen's eggs - a process that often takes several months. This is a major disadvantage when vaccines against novel viruses such as SARS-CoV-2 have to be available quickly.

RNA vaccines

Fast production of large quantities possible

RNA vaccines do not contain viruses, only the pathogen gene in the form of so-called messenger RNA. This messenger or messenger RNA instructs the cells to produce the antigen. It can be produced relatively easily and quickly in the laboratory from a DNA sequence of the virus. This enables the production of large quantities of a vaccine in a short period of time.

Conventional vaccines

Large amounts of virus are required

Growing large numbers of live viruses to make a vaccine has potential safety risks. Strict precautions must be taken to prevent a virus from escaping or employees from becoming infected in the manufacturing process.

RNA vaccines

No viruses required

RNA-based vaccines are generally considered to be very safe as no viruses are required in the manufacturing process. They are made purely synthetically and are not infectious. Small amounts of virus are only required for gene sequencing.

Conventional vaccines

The antigen is injected

With vaccination, the virus antigen is injected into the body. As soon as the immune system has recognized the antigen, specific antibodies and memory cells are produced, which react on renewed contact with the real pathogen. The body can fight off the disease - it is immune to the pathogen.

RNA vaccines

The body makes the antigen itself

In the case of RNA vaccines, the vaccine only gives the body the genetic information of the virus. The body cells use this artificially produced genetic information to produce the specific antigen themselves. If the vaccinated person comes into contact with the virus later, the immune system recognizes the antigen and can fight the infectious disease in a targeted manner.

Conventional vaccines

Individual production processes necessary

Every new vaccine requires a tailor-made production process. This includes complex cleaning processes as well as elaborate test tracks. It is therefore not really possible to react quickly to virus mutations.

RNA vaccines

Standardized processes simplify production

The production process for RNA vaccines can be standardized and does not have to be adapted for each new vaccine. Therefore, it is possible to react more quickly to the mutations of a pathogen.

Further information on the topic:

The worldwide clinical development program for a COVID-19 mRNA vaccine

There is a global research effort into developing COVID-19 vaccines and several companies are working on it, including BioNTech.

BioNTech is a next-generation global immunotherapy company based in the heart of Europe. Our commitment aims to unlock the full potential of novel therapies for cancer and infectious diseases. After the outbreak of the COVID-19 pandemic, we used our extensive mRNA toolkit, based on our decades of experience in the field of mRNA technology and our deep understanding of the immune system, to strive for an accelerated response to the unresolved medical requirements of the pandemic.

We launched a unique clinical development program for a COVID-19 vaccine called Project Lightspeed in January 2020. Through cooperation with our partner companies Fosun Pharma and Pfizer, we expanded our approach globally in March 2020. Together with our partners, our commitment aims to develop and test potential vaccines against COVID-19 in accordance with high ethical standards and sound scientific principles. The safety and well-being of vaccinated people are always our top priority.

BioNTech developed five different clinical COVID-19 vaccine candidates using multiple mRNA formats to allow thorough evaluation in clinical trials before making a final decision on the optimal vaccine candidate. Two mRNA vaccine candidates have emerged as strong candidates based on safety assessments and achieving the desired immune response.

After a thorough review of the preclinical and clinical data from the phase 1/2 studies and in consultation with the worldwide regulatory authorities, BioNTech and Pfizer decided to transfer their lead vaccine candidate to a phase 2/3 study. This global study plan includes approximately 44,000 subjects aged 12 and over from a diverse population, including ethnic minorities and high-risk groups. The study will be conducted in approximately 154 clinical trial centers around the world, including trial centers in Germany, the USA, Argentina, Brazil, Turkey and South Africa. The study is planned as a randomized, observer-blinded study with a one-to-one ratio of vaccine candidate to placebo to provide safety, immune response and efficacy data required for regulatory review.

On December 2, 2020, BioNTech and Pfizer received preliminary approval from the UK Medicines & Healthcare Products Regulatory Agency (MHRA) for the emergency use of their COVID-19 mRNA vaccine. In addition, an emergency license for the USA was granted on December 11, 2020.

“We selected our COVID-19 mRNA vaccine candidate for the phase 2/3 study after carefully evaluating all of the data collected so far. This decision expresses our primary goal of bringing a safe, well-tolerated and highly effective vaccine onto the market as quickly as possible. At the same time, we will continue to examine and evaluate our other vaccine candidates as part of a differentiated COVID-19 vaccine portfolio. "


Prof. Dr. Ugur Sahin, chairman of the board