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mRNA vaccines to address the COVID-19 pandemic
What is a mRNA vaccine and how do mRNA vaccines work?
Messenger ribonucleic acid (mRNA) vaccines are a novel technology that stimulates the body’s own immune response. These vaccines contain information from messenger RNA, including the “blueprint” or code of a specific virus trait (virus antigen). The information enables the body to produce this antigen on its own: mRNA transfers the information for the production of the antigen to our cell machinery that makes proteins. Cells in our body then present the antigen on their surface and thus 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.
With COVID-19, the entry of the coronavirus into the host cell in humans is intervened by the coronavirus spike protein that is located on the surface of the virus. mRNA vaccines against COVID-19 are designed to provide our bodies with the code to produce the non-infectious virus spike protein to instruct the cell’s machinery to help stimulate a natural immune response. This response is achieved primarily through T-cells and the production of neutralizing antibodies, which aim to prevent SARS-CoV-2 infection (and its associated disease, COVID-19). If a vaccinated person later comes into contact with SARS-CoV-2, the immune system will recognize the surface structure and will be able to combat the virus and eliminate it. Neutralizing antibodies targeted at SARS-CoV-2 are circulating in your body and will immediately bind to the virus, “neutralize” it and prevent it from entering the cell, thus protecting you from getting sick. T cells help the immune system to fight intracellular infections and can also kill the infected cells directly.
Thus, in contrast to conventional vaccines, a mRNA vaccine does not contain any viral proteins itself, but only the information that our own cells need to produce a virus trait that triggers the desired immune response. mRNA technology has enabled the design of multiple vaccine candidates against COVID-19.
How mRNA-based vaccines work
The vaccine encodes the presentation of small, harmless fragments of the COVID-19 virus to the immune cells, so they “learn” how to recognize and attack the virus. This allows for a quick and specific immune response upon exposure with the actual virus, thereby preventing its replication and spread in the human body and to other individuals.
How do mRNA vaccines differ from “conventional” vaccines?
How are conventional vaccines manufactured?
Conventional vaccines usually contain weakened or inactivated disease-causing organisms or pathogen proteins (antigens) to stimulate the immune response of the body, which is prepared to react faster and more effectively if it is exposed to the infectious agent in the future.
Production of conventional viral vaccines in bioreactors is a well established process, though lengthy and cumbersome: it includes several steps like preparation of seed virus, fermentation, harvesting and purification and can take several months. Also, the handling of large volumes of live virus is necessary.
How are mRNA vaccines manufactured?
mRNA vaccines take a different approach: they use the process in which the cells themselves build proteins from the information encoded in the messenger RNA (mRNA). This “blueprint” is translated by the body to synthesize specific proteins (antigens).
A mRNA vaccine consists of a strand of mRNA that codes for a disease-specific protein (antigen). 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): lipid polyplexes form LNPs.
Once the mRNA vaccine is injected into a person, the lipid nanoparticles protect the mRNA from degradation and help it reach the cells where the information contained in the mRNA strand is read to produce the antigen protein that eventually triggers the desired immune response.
The interest in mRNA technology as a platform for vaccines has increased during the last two decades. A vaccine based on mRNA is faster to manufacture than conventional vaccines, as only the blueprint and not the antigen itself needs to be produced.
RNA vaccines and conventional vaccines
The manufacturing process for RNA vaccines may speed up the response to infectious disease outbreaks. Read on to see how RNA vaccines differ from conventional vaccines.
Can take months and is complex
Most vaccines against viral diseases are made from viruses grown in chicken eggs or mammalian cells. The process of collecting the viruses, adapting them to grow in the lab, and shipping them around the world can take months and is complex. For newly emerging viruses like SARS-CoV-2, for which a new vaccine is needed as quickly as possible, these steps may slow down development.
One week to generate an experimental batch
The RNA (which encodes an antigen of the infectious agent) is made from a DNA template in the lab. The DNA can be synthesized from an electronic sequence that can be sent across the world in an instant by computer. Currently it takes about a week to generate an experimental batch of an RNA vaccine.
Large quantities of virus
Growing large quantities of virus to make each batch of vaccine create potential hazards.
No virus needed
No virus needed to make a batch of an RNA vaccine. Only small quantities of virus are used for gene sequencing and for the vaccine testing.
The antigen, a piece of the virus, is injected
The antigen (a piece of the virus) is injected into the body. Upon recognizing the antigen, the immune system produces specific antibodies in preparation for the next time the body encounters the pathogen.
The RNA is injected
The RNA is injected into the body and enters cells, where it provides instructions to encode antigens. The cell then presents the antigen to the immune system, prompting T-cell and antibody responses that fight the disease.
Requires a bespoke production process
Each new vaccine requires a bespoke production process, including complex purification and testing.
The production process can be standardized
The production process can be standardized. We anticipate that the production process for RNA vaccines may be able to be scaled and standardized; potentially enabling replacement of the sequence encoding the target protein of interest for a new vaccine with minimal changes to the vaccine production process.
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The global clinical development program for a COVID-19 mRNA vaccine
There is a global research effort to develop COVID-19 vaccines and a number of companies are working towards that goal, including BioNTech.
BioNTech is a global next generation immunotherapy company based in the heart of Europe. We aspire to harness the full potential of novel therapies for cancer and infectious diseases. After the onset of the COVID-19 pandemic we leveraged our broad mRNA toolkit to pursue an accelerated response to the unmet medical needs of the pandemic based on our decades long experience in mRNA technology and the deep understanding of the immune system.
We started a unique clinical development program, Project Lightspeed, for a COVID-19 vaccine in January 2020 and extended it to a global approach through collaborations with our partners Fosun Pharma and Pfizer in March 2020. Together with our partners, we are committed to developing and testing potential vaccines for COVID-19 in accordance with high ethical standards and sound scientific principles, always making the safety and well-being of vaccinated individuals our top priority.
BioNTech developed five different clinical COVID-19 vaccine candidates using multiple mRNA formats to allow for a thorough assessment in clinical trials before making a critical decision on the optimal vaccine candidate. Two investigational mRNA vaccines emerged as strong candidates based on safety assessments and achieving the desired immune response.
After extensive review of preclinical and clinical data from Phase 1/2 clinical trials, and in consultation with global regulators, Biontech and Pfizer chose to advance their lead vaccine candidate into a Phase 2/3 study. This global study plans has enrolled approximately 44,000 participants aged 12 years and older from a diverse population, including ethnic minorities, as well as high risk population in approximately 154 clinical investigational sites around the world, including study sites in Germany, U.S., Argentina, Brazil, Turkey and South Africa. The trial is designed as a 1:1 vaccine candidate to placebo, randomized, observer blinded study to obtain safety, immune response and efficacy data needed for regulatory review.
The COVID-19 vaccine has now been granted a conditional marketing authorization, emergency use authorization or a temporary authorization in a total of more than 40 countries.
“We selected our COVID-19 mRNA vaccine candidate for the phase 2/3 trial upon diligent evaluation of the totality of data generated so far. This decision reflects our primary goal to bring a safe, well-tolerated, highly effective vaccine to the market as quickly as possible while we will continue to evaluate our other vaccine candidates as part of a differentiated COVID-19 vaccine portfolio.“
Prof. Ugur Sahin, M.D., Chief Executive Officer