A scientific tour de force in genetic engineering – From the Corona vaccine soon to the treatment of cancer?

The Trump administration, large parts of the U.S. Congress, the Brazilian president, most of the German AfD, and significant parts of the Swiss SVP have during the Covid crisis actively undermined science-based health and safety protections, cast aside scientific evidence, and in many instances questioned scientific integrity itself. The recent success in developing a vaccine against the corona virus is however nothing less than one of the greatest triumphs of science in recent years. The developers of the BNT162b2 vaccine from the German company BioNTech, the German-Turkish couple Ugur Sahin and Özlem Türeci, were even named «Financial Times Person of the Year in 2020». It was only the second time in the 50-year history of this award that it went to a scientist (in 2000 it went to American biotechnologist Craig Venter, and in 1999 the «Financial Times Person of the Century»award went to the mathematician and computer pioneer John von Neumann). BioNTech collaborated with the U.S. company Pfizer on development, logistics, finance, clinical trial oversight, and global manufacturing (the U.S. media often mistakenly refer to this as “Pfizer vaccine”, however, Pfizer just licensed the method and is thus not involved at all in China, where the license for the distribution and manufacturing was acquired by the Chinese company Fosun). Nevertheless, there exists widespread skepticism about the vaccine in the general public, which shall be motivation to take a closer look at this vaccine.

Vaccination against viral and bacterial diseases is one of the greatest success stories of modern medicine. It has greatly reduced the incidences of infectious diseases such as measles, mumps, diphtheria and rubella, and eradicated others such as smallpox. However, traditional vaccine approaches do not prove as effective against rapidly evolving pathogens such as influenza or newly emerging threats such as the Ebola or the Zika viruses. In general, a vaccination stimulates the immune system itself to develop pathogen-specific immunocompetence by producing the body’s own protective substances without undergoing the entire infectious disease itself. Live or dead vaccines which do not themselves trigger the disease are normally used for this purpose, attenuated pathogens that are still capable of reproducing in the former case and dead ones in the later case (i.e. no longer capable of reproducing, in the case of viruses one cannot actually speak of living organisms). Cowpox material served as an early form of vaccination, hence the word vaccination from the Latin “vacca ” for cow. These conventional forms of vaccines are costly and very lengthy to produce, require special safety precautions when handling the material, and often need active ingredient boosters, so-called adjuvants, to achieve the desired immune response.

This is where the immense advances in genetic engineering in recent years and the development of “genetic vaccines” come into play. Due to their greater efficacy, better safety, and shorter manufacturing times they can have an immense impact on the future development of vaccines. Genetic vaccines contain the genetic information of the pathogen which, after administration, is translated into corresponding proteins by the body’s cells themselves. As in a genuine viral infection, this triggers a defense reaction by the immune system. So-called “mRNA vaccines” are attracting particular attention today: They work by introducing a «mRNA» («messenger RNA») sequence into the body that encodes a disease-specific protein (an antigen). This genetic information serves as a blueprint according to which the cells of vaccinated individuals can now produce the corresponding viral protein themselves. Once the protein is produced in the body, it is recognized by the immune system as non-genuine and gets destroyed by the corresponding antibodies and memory T cells. This prepares the vaccinated person’s body to fight the real antigen (i.e. the real virus). In the case of the SARS-CoV-2 virus, the target protein encoded in the mRNA is the special corona spike protein that sits on the surface of Sars-CoV-2 and docks onto the host cells. The body is thus enabled to destroy cells with this protein, just as if it had been infected with the real corona virus and is now immune against it.

The use of mRNA has several advantageous properties over conventional vaccines based on dead or attenuated live viruses:

1. Safety: mRNA vaccines are not made with pathogen particles or inactivated pathogens, so they are not infectious. mRNA also cannot penetrate DNA (unfortunately, on this point there is considerable misinformation spread via social media). Therefore, there is no risk of neither infection nor alteration of DNA. Moreover, mRNA is rapidly degraded by normal cellular processes. Without protection, this occurs even within minutes by enzymes present everywhere in the body. Its in vivo half-life can (and must) be regulated by various modifications and delivery methods (see below). mRNA vaccines are thus safer than conventional vaccines.
2. Efficacy: Clinical trial results from numerous different providers indicate that mRNA vaccines elicit a very reliable immune response and are well tolerated by healthy individuals with few side effects. mRNA is the minimal genetic vector, so anti-vector immunity is avoided and mRNA vaccines can be administered repeatedly.
3. Cost-effective and rapid production: mRNA vaccines targeted at specific viruses can be produced very quickly, at low cost, with readily available materials and in large quantities. All their production is done in the laboratory, and the process can be standardized and scaled up, enabling rapid response to future large outbreaks and pandemics. The launch of research activities to develop an mRNA vaccine against SARS-CoV-2 worldwide was the publication of the genetic sequence of the virus on January 10, 2020. As early as March 16 did the first COVID-19 vaccine candidate enter human clinical trials. Billions of vaccine doses will be available next year.

Because mRNA degrades so quickly in the body, its usefulness has been very limited until recently. For this reason, earlier clinical trials in influenza and rabies were not as successful as hoped. Larger amounts of RNA were needed because their effect was less potent. Until the development of the BNT162b2 vaccine against Covid, there had thus been no approval of an mRNA vaccine for use in humans. This is where progress has been made: In order to facilitate transport and to preserve the mRNA for a sufficient length of time until it reaches the interior of the cell, the RNA strand is incorporated, packaged, so to speak, into a larger molecule (into so-called liposomes). The mRNA vaccines must therefore be frozen (like conventional vaccines) and kept refrigerated until shortly before administration.

However, mRNA vaccines are not only being developed against infectious diseases, but also against various types of cancer, where they are also showing encouraging results. Sahin and Türeci, for example, were primarily focused on cancer treatments before the Covid pandemic. Cancer vaccines are a form of immunotherapy in which the vaccine triggers the immune system to turn itself against the cancer. For example, research has long been conducted on cell vaccines, in which the mRNA sequence in the vaccine is designed to code for cancer-specific antigens. There are already more than 50 clinical trials for mRNA vaccines for a range of cancers, including blood cancers, melanoma, glioblastoma (brain tumor) and prostate cancer. For example, researchers sequenced the genomes of tumors from patients with melanoma. They created the respective mRNA that encode mutant proteins specific to the patients’ cancers and that could thus trigger an immune response, and used those to create patient-specific vaccines. Eight of thirteen vaccinated individuals remained tumor-free up to two years later.

It may well be that the Covid-19 pandemic will serve as the launching pad for a broad breakthrough in the treatment of cancer and infectious diseases through genetic vaccines and patient-specific drugs. Unfortunately, however, it will probably take a little more time before the science skeptics, genetic engineering opponents and vaccination opponents understand this.