Researchers have spent decades experimenting with DNA and mRNA-based vaccines, overcoming challenges with targeted immune responses, rapid replication, and vaccine stability. Covid proved that these technologies are ready for use, and that’s just the beginning.
Advantages of Genetic Vaccines
Traditional vaccines use weakened cells from the targeted pathogen to trigger an immune response. While this method is safe and effective, and has helped to protect the world and, in some cases, eradicate infectious diseases, genetic vaccines have several advantages. In particular, DNA and mRNA vaccines are:
- Faster to make at scale. A traditional vaccine requires extensive culturing and replicating of pathogenic cells, which takes time and is slow to scale up. However, genetic vaccines are essentially simply chemicals awaiting catalyzation, and can be produced quickly in large quantities. Once researchers have the DNA of the pathogen, they can rapidly make vaccines, even in large amounts.
- More accurately targeted. While whole-inactivated vaccines rely on triggering the body’s natural immune response, it may not always work, or may not always work as intended. Depending on a person’s existing exposure and immunity, a recipient may clear the pathogen before the vaccine is fully effective. Instead of triggering a traditional immune response and prompting your body to learn how to make a specific antigen, genetic vaccines directly carry the instructions your cells need to make the antigen, and, in the case of the Covid vaccine, targets the pathogen in a specific stage of its development.
- Provide improved immune response. Genetic vaccines are more effective at clearing a pathogen than traditional vaccines, because they trigger not only antibody production, but also stimulate the production of T cells. The combined antibody+T cell response makes these vaccines more effective at quickly eliminating pathogens, and also provides more protection from mutations over time.
Finally, mRNA has some key advantages over DNA-based vaccines. Vaccines that use DNA provide the DNA with the instructions to make the messenger RNA that transmits antibody information to other cells. However, this information is only sent during the cell division and replication process. By bypassing DNA and providing the mRNA directly, these vaccines accelerate an immune response and work more quickly.
Current Innovations in Genetic Vaccines
While mRNA vaccine technologies had been amply studied and much of the necessary infrastructure was in place to create these vaccines, Covid was a global catalyst that sparked a dramatic increase in investment, interest, and expansion of these vaccines. As a result, we are poised to use these technologies to fight a host of diseases that have been difficult or impossible to prevent using traditional means. Some of the most exciting research is being applied to:
- Flaviviruses. Viruses in the Flaviviridae family cause millions of deaths every year, and are a growing threat to public health. These viruses include the viruses that cause West Nile, dengue, tick-borne encephalitis, yellow fever, Zika, and more. One of the reasons these diseases have been so difficult to vaccinate for is the prevalence of antibody-dependent enhancement (ADE) of infections, where the body’s antigens bind to a premature stage of pathogen and therefore render the body more vulnerable to the virus, instead of less. In the case of Zika and dengue, a second exposure is often more dangerous and has worse health outcomes than the first. As mentioned above, because mRNA vaccines can target a specific phase of pathogen development, they are far more likely to be effective against these diseases.
- HIV. HIV is an incredibly difficult pathogen to treat with a vaccine, due to a wide range of factors, including the way in which it fosters immune tolerance, mutates within the body, and the range of different immune responses it triggers within the body. Researchers are eagerly studying mRNA vaccines to prevent HIV, hopeful that the way in which these vaccines create antigens as well as triggering T-cell production can protect people from the disease.
- Cancer. It seems as though cancer is the “holy grail” of vaccines, and we may be getting close. Cancer is incredibly difficult to prevent and fight because the pathogenic cells are related to the body’s own cells, and therefore do not trigger the appropriate immune response. However, cancer tumors do have their own DNA that is distinct from the body’s normal DNA, making it possible to treat cancer with custom, individual-specific vaccines. Many trials are currently underway.
- Autoimmune diseases. A few years ago, it may have seemed unlikely that we could develop a vaccine for autoimmune diseases like arthritis, IBS, lupus, multiple sclerosis, and other diseases caused by an abnormal immune response. In a sense, autoimmune diseases are the opposite of the ADE mentioned above: instead of increasing antigen tolerance over time, the body becomes increasingly intolerant of specific antigens, causing a wide range of health conditions. Traditionally, treating these conditions without broadly suppressing the immune system has been a huge challenge, but earlier this year an mRNA vaccine against multiple sclerosis was successfully tested in mice. Instead of targeting the over-reactive cells, the vaccine appears to target the resulting disease-causing cells and suppress them without increased inflammation or affecting tolerance to other unrelated antigens.
The Future of Genetic Vaccines
Another lasting impact of Covid is not just the development of these vaccine technologies, but also the social, cultural, and political impact of vaccines on public health. The past year has caused a widespread call for change, including in these important areas:
- Updated vaccine approval analysis and procedures. Although the Covid vaccine was created, approved, and distributed in record time, it highlit the dramatic need for regulatory reform. Many experts in the pharma industry feel that the current regulatory review process is outdated and ill-equipped to understand the current tools and technologies being used to develop vaccines. There are calls for a single, global regulatory review and approval process, rather than different regional approval processes. Vaccines could be produced more quickly if ethical and regulatory reviews were conducted in parallel, rather than sequentially, and distributed more quickly if manufacturers were allowed to produce vaccine doses at scale during the regulatory process, rather than afterward.
- Global pharmaceutical cooperation and transparency. The world owes an enormous debt of gratitude to Professor Zhang Yongzhen, who made the extraordinary decision to publish the SARS-CoV-2 genome within hours of sequencing it. However, he paid a high price for his decision, and the next outbreak will probably be accompanied by more specific rules and protocols. In addition, regulators claim that they could approve vaccines more quickly if there were more transparency in data from drug companies. While the need to protect intellectual property is significant, the health of the world also relies on free, open, and transparent communications between experts, researchers, regulators, and scientists who are fighting diseases.
- Better public health communication. If the Covid vaccines have had one notable failure, it is among the large numbers of people who do not want to take it. Throughout the pandemic, public health information around the world has been heavily politicized, leading to mistrust and misinformation. And while we might think that people who don’t want the vaccine are simply un-informed, it is also unfortunately true that there are many historic instances where governments approved and promoted vaccines that turned out to be harmful, or used public health authority to further a political agenda. We all need to be better next time, because virologists assure us there will be a next time.
The world’s pharmaceutical industry has not only risen to the challenge of the biggest global health threat in our lifetimes, but they have also used this opportunity to develop cutting edge research and technologies that can improve health outcomes for decades to come. At grapefrute, we look forward to the day when so many of these diseases will be a matter of history, and are proud of the small role we have played in helping these companies build the teams that will take them into the future. If you want to be a part of the latest medical and vaccine science, contact grapefrute today.