From COVID to Cancer, Understanding the Applications of mRNA Vaccines

Traditional Vaccines vs mRNA Vaccines

According to an article by Penn Medicine, the traditional vaccine model involves using a weakened or inactive version of the target virus to stimulate the immune system, forcing a response against the disease. While these vaccines have been extraordinarily helpful in eliminating many viral infections, there are challenges, such as time, cost, and modification. For rapidly evolving viral infections, these vaccine methods may be futile.

Conversely, mRNA vaccines are based on a genetic code that indicates to the body that it needs to produce specific proteins in the immune system. Since these kinds of vaccines function in an almost “plug-and-play” manner, they can be developed and altered quickly at a lower cost.

According to the COVID-19 Real-Time Learning Network, mRNA vaccines were first explored in the 1990s. However, early iterations of these antivirals were ineffective as mRNA can be unstable and difficult to work with. Even before the era of COVID vaccines, mRNA vaccines were being explored for HIV, rabies, Zika virus, influenza, and more.

mRNA vaccines are composed of lab-made single-stranded RNA molecules, messenger RNA, encapsulated with nanoparticles. When ribosomes translate the mRNA in the cytoplasm, it creates a protein antigen that triggers an immune response. The COVID-19 Real-Time Learning Network notes, “the mRNA does not enter the nucleus and therefore cannot be incorporated into the genome. Its presence in the cell is transient, and it is quickly metabolized and eliminated via cellular processing mechanisms.”

Applications of mRNA Vaccines

mRNA vaccines have been explored for decades; however, the funding allocated to research on these vaccines for COVID-19 may fuel and enhance research on other applications such as other infectious diseases, cancer, genetic illnesses, allergies, and more.

COVID-19

It is nearly impossible to discuss the benefits and applications of mRNA vaccines without discussing the extensive public health benefits that mRNA COVID vaccines have had throughout the pandemic. An article published by the Commonwealth Fund in December 2022 estimated that the over 655 million COVID-19 vaccines administered in the United States had prevented 3,255,656 deaths, 18,585,131 hospitalizations, and 119,851,779 infections.

The COVID-19 pandemic is a first-hand example of the versatility and benefits of mRNA vaccines. As the SARS-CoV-2 continued to evolve, researchers altered vaccines to address later iterations of the disease.

Other Infectious Diseases

According to Penn Medicine, mRNA vaccines are being explored for various infectious diseases, including other SARS viruses, MERS, Clostridiodes difficile, HSV-2, hepatitis C, HIV, influenza, leptospirosis, malaria, norovirus, and tuberculosis, among others.

In April 2022, Moderna began early trials of an influenza mRNA vaccine. Since influenza is a virus that mutates rapidly, an mRNA vaccine may ease the development of vaccines that are effective for future mutated forms.

Additionally, in March 2022, the NIH launched clinical trials on three experimental mRNA HIV vaccines. This clinical trial enrolled participants between 18 and 55 across the US to test immune responses to the vaccine. The results of this study are anticipated in July 2023.

“Finding an HIV vaccine has proven to be a daunting scientific challenge,” said Anthony S. Fauci, MD, NIAID director at the time, in a press release. “With the success of safe and highly effective COVID-19 vaccines, we have an exciting opportunity to learn whether mRNA technology can achieve similar results against HIV infection.”

Cancer

The versatility of COVID vaccines has allowed researchers to extrapolate the mechanisms used to develop COVID vaccines for other illnesses besides infectious diseases, including cancer. Despite plans to implement a similar foundation, there are variations in the uses, challenges, and outcomes of an mRNA vaccine for cancer as opposed to COVID-19.

The most remarkable and fundamental difference is the basis of use. As many understand, mRNA vaccines for COVID-19 are meant as a prophylactic treatment to prevent infection; however, using an mRNA vaccine to prevent cancer is impractical. Instead, researchers hope to repurpose mRNA vaccines as an interventional approach that allows a patient’s immune system to attack tumor cells.

In a commentary published in the American Journal of Medicine, Drew Weissman, MD, PhD, a professor of Infectious Diseases at the Perelman School of Medicine, and his colleagues note that mRNA vaccines can trigger robust cytotoxic T-cell responses. T cells can work to kill cancer cells when altered or triggered to do so. This treatment hypothesis is comparable to immunotherapy treatments such as CAR T-cell therapy.

“A successful therapeutic cancer vaccine should induce strong T cell responses, particularly with CD8+ T cells, which have a known capacity to kill malignant cells,” said Norbert Pardi, PhD, a research assistant professor of Infectious Diseases in the Perelman School of Medicine, to Penn Medicine. “Therapeutic cancer vaccines would be given to cancer patients with the hope that those vaccine-induced cytotoxic T cells would clear tumor cells.”

Although these methods may be beneficial and effective in treating cancer, some challenges come with these mechanisms. Chief of these challenges is the variability in cancer and tumor composition. Tumor antigens are often specific to each patient, differing even within the same type of cancer. Each patient would require their own version of a cancer vaccine depending on their tumor antigens. Fortunately, mRNA vaccine flexibility eases some of the burdens of this type of precision medicine.

As researchers and institutions race to find new cancer treatments, Moderna and Merck have collaborated on an mRNA cancer vaccine, entering phase II clinical trials as recently as December 13, 2022. Early clinical trials showed that combined with Keytruda, this mRNA vaccine reduced cancer recurrence or death by 44% in patients with stage 3 or 4 melanoma.

Allergies

mRNA vaccines have also been explored as a prophylactic treatment for allergies. A 2015 study published in the Journal of Immunology analyzed the efficacy of mRNA vaccines on mice with grass pollen allergies. Researchers found that the immunization suppressed TH2 cytokines, IgE response, and lung eosinophilia, thus, mediating allergic reactions. Researchers in this study concluded that mRNA vaccines “combine effective prevention of allergic sensitization with a commendable safety profile.”

According to Penn Medicine, researchers are also currently looking at the use of mRNA vaccines to stop the production of IgE, which can trigger anaphylaxis in those with severe allergies.

Other Illnesses

Penn Medicine also notes that mRNA vaccines are being explored to treat genetic diseases such as cystic fibrosis and sickle cell anemia. For cystic fibrosis, researchers are looking to determine whether an mRNA vaccine can instruct the lungs to create healthy cystic fibrosis transmembrane conductance regulators (CFTR), as a mutated version is the cause of the disease. Researchers hope to repurpose mRNA vaccines for sickle cell anemia, allowing them to instruct the cell to repair genetic defects.

mRNA therapies are also considered a gene editing technology for conditions such as heart failure, ALS, and dementia.