COVID-19's silver lining: speeding vaccine tech for other diseases
( UPI )
Thanks to the COVID-19 pandemic, the previously little-known science behind mRNA technology has gone mainstream -- and now experts believe more shots using the approach for a variety of diseases are in the cards.
For example, the ability of mRNA vaccines to boost production of a key protein in skin health could make them a valuable tool to help prevent skin cancer, researchers at Oregon State University said Thursday.
And last week, officials with Pfizer-BioNTech, the partnership behind one of the two mRNA vaccines that protect against COVID-19, announced they will use the approach to develop a vaccine against shingles.
Chances are most people in the United States probably never heard of mRNA vaccines before the COVID-19 pandemic started in March 2020.
However, scientists have been working with the approach for more than two decades, and many believe it could hold the key to producing vaccines to combat some of the world's most challenging diseases, from cancer and HIV to the flu and malaria, experts told UPI.
"The mRNA COVID-19 vaccines greatly exceeded expectations and seemed to perform best of all the vaccine types tested, which gives reason to believe that mRNA vaccines against other diseases could be as effective," Stephen S. Morse, an expert in emerging infectious diseases, told UPI in an email.
"Another important reason is simplicity -- the process is about the same for all mRNA vaccines, so it's fairly easy to switch as new mRNA vaccines are developed," said Morse, a professor of epidemiology at Columbia University in New York City.
How mRNA vaccines work
RNA, or ribonucleic acid, is essential for all life.
Like DNA, or deoxyribonucleic acid, which essentially determines the genetic makeup of all living organisms, RNA is used by cells for a variety of tasks, according to the National Human Genome Research Institute.
One of these functions is messenger RNA, or mRNA, which carries instructions from DNA to cells to make proteins that aid in everything from digestion to stimulating the body's immune response, the institute says.
The COVID-19 vaccines from Moderna and Pfizer-BioNTech contain mRNA that is designed to train cells in the human body to make specific proteins, called antibodies, that help the immune system fight the virus, according to the Centers for Disease Control and Prevention.
These proteins target the so-called "spike protein" on virus cells, preventing them from replicating and spreading throughout the body, Dr. Eric Topol, chair of innovative research at the Scripps Research Institute in La Jolla, Calif, told UPI in a phone interview.
The spike protein, so named because it sticks out from the surface of coronavirus cells, provides an obvious target for the vaccines, Topol said.
However, researchers only knew about the spike protein because of an earlier outbreak of a coronavirus, the SARS outbreak of 2003, so identifying similar targets for other diseases may take time.
Still, mRNA can essentially be programmed to create other proteins that help fight off diseases because "it's such a flexible platform," Topol said.
"We can develop mRNA, wrap it in a nanoparticle and inject it into the human body to address multiple pathogens," he said.
While most vaccines "require growing the pathogen first, mRNA vaccines only require genetic sequence data," or the genetic make-up of a virus or disease, Morse added.
"This greatly shortens the time from identification to product," he said.
Researchers at the Oregon State University College of Pharmacy believe, for example, that mRNA vaccines can be used to stimulate production of a protein called TR1, which plays an important role in the skin's antioxidant network, they said in a study published Tuesday by the Journal of Investigative Dermatology.
If so, the approach could be used to vaccinate against skin cancers, the most common form of the disease in the United States, including melanoma, they said.
That's because these cancers are caused by exposure to the sun's ultraviolet radiation, which leads to oxidative stress, or an imbalance between the production of cells called free radicals and antioxidant defenses against them, Oregon State researcher Arup Indra said in a press release.
This imbalance in the skin raises a person's risk for skin cancer, said Indra, a professor of pharmaceutical sciences.
Meanwhile, researchers at Duke University are exploring whether mRNA can be used to prevent all forms of cancer by teaching the immune system to recognize the genetic mutations that cause the disease before they form.
A vaccine against cancer is not unprecedented.
The human papilloma virus, or HPV, vaccine helps prevent cervical cancer. The vaccine protects against infection with the virus, which is known to cause the cancer.
Before development of the HPV vaccine, cervical cancer was the leading cause of cancer death among women in the United States. Cases of the cancer have declined by 20% since the vaccine became available.
mRNA also could be used to boost production of cells called chimeric antigen receptors-T, or CAR-T, which can help repair damage to the heart caused by heart disease, researchers at the University of Pennsylvania in Philadelphia said in a study published Tuesday by the journal Science.
Injecting mice with mRNA designed to guide the production of CAR-T reduced fibrosis, or tissue damage, and restored heart function, they said.
Researchers at Duke University's Human Vaccine Institute are exploring whether mRNA can be used to speed production of antibodies against HIV.
In a review of their research published last year, the scientists noted that about one-third of people infected with the virus develop antibodies against it years later.
They are hoping that mRNA can be used to bring that process forward by a few years and prevent infection in the first place.
Each year, working under the auspices of the World Health Organization, researchers determine the formulation of the seasonal flu vaccine, based on predictions of what strains of the virus will be in circulation that year.
In a good year, the flu vaccine prevents serious illness from the virus about 60% of time, according to the CDC.
As an alternative, researchers at the Icahn School of Medicine at Mount Sinai in New York City and the University of Pennsylvania are studying whether mRNA can be used to produce a "broad" antibody response that helps the immune system fight off all strains of the virus.
In the mice used in a study they published last summer, mRNA vaccines designed to produce anti-flu antibodies did protect against infection with multiple strains of the virus.
Although the World Health Organization cleared the first anti-malaria vaccine in October, the shot only prevents severe illness from the mosquito-borne virus, which strikes 500,000 people globally, about 30% of the time.
Part of what makes malaria so deadly is that people can be reinfected with the virus easily due to a protein called PMIF, which kills "memory" T cells -- essentially an immune system response that continues to recognize viruses for long periods, according to researchers at Yale University.
Using a different form of RNA, called self-amplifying, or saRNA, they are hoping to create a vaccine that instructs cells in the human body to produce an antibody against PMIF, allowing immunity against malaria to live on, one of the researchers, Dr. Richard Bucala, told UPI in an email.
With saRNA, "the RNA encoding the antigen replicates inside the vaccinated muscle cell," said Bucala, who is chief of rheumatology, allergy and immunology at the New Haven, Conn.-based school.
"This is essential to produce the cell-mediated immunity necessary for a malaria vaccine, because antibody-based immunity is insufficient," he said.
Pfizer and BioNTech announced plans earlier this month to partner and develop an mRNA vaccine to protect against shingles.
The companies said they plan to use the same antigen and mRNA technologies in their COVID-19 vaccine to create the vaccine for shingles, also known as herpes zoster.
The new vaccine would contain mRNA designed to boost production of antibodies against shingles, similar to how it works with COVID-19, they said.
Given that scientists know well the genetic makeup of herpes zoster, developing an mRNA vaccine against it makes sense, said Columbia's Morse, who is not part of the project.
Many of these mRNA-based vaccine are likely several years away from being used, as clinical trials in humans still need to be conducted for most of them, Topol said.
However, the COVID-19 pandemic has demonstrated that it is possible to hasten the development process when needed, he said.
"There are many potential silver linings to this pandemic, believe it or not, and despite all the suffering, the development of mRNA vaccines for a number of diseases is one of them," Topol said.
The development of mRNA vaccines against COVID-19 "is the most momentous advance in biomedicine, [and] we've gotten so much better at their development over the past couple of years that the likelihood of success is higher" with other diseases, he said.