Cleveland Clinic researchers believe they have found a way to improve COVID-19 vaccines by strengthening and prolonging their effectiveness. Those researchers took a page from the herpes virus to help human cells better learn from messenger RNA COVID-19 vaccines how to recognize and subsequently fight the virus that causes COVID-19, the Clinic announced Monday.
Messenger RNA (mRNA) vaccines, like the original COVID-19 vaccines produced by Pfizer and Moderna in 2020, teach the body's cells how to make copies of the coronavirus' spike protein, according to the American Heart Association. If someone is exposed to the real virus later, their body will recognize it and know how to fight it off, according to the Centers for Disease Control and Prevention.
"mRNA vaccines give our bodies the genetic instructions they need to build pieces of the pathogen that our immune systems can respond to. In this way, mRNA vaccines act a lot like the viruses we fight against," said Dr. Jae Jung, director of Cleveland Clinic's Global Center for Pathogen & Human Health Research.
Viruses have their own genetic makeup, but they don't know how to carry out the instructions written in their genes. As a result, they trick infected host cells into reading the foreign genetic material and making proteins for the virus. Jung's research team took this knowledge and used it to improve how host cells read genetic material in mRNA vaccines.
Viral genes use different DNA and RNA sequences than human genes, making it difficult for host cells to produce the protein the virus is asking for. Jung likened this to saying "Hello" in different languages — infected cells can determine what protein the viral genes want them to produce, but the language difference complicates the instructions.
“Think of it like using different spellings of the same word when writing out instructions,” said Dokyun "Leo" Kim, a graduate student in Jung's lab. “Infected cells can figure out what protein the viral genes want them to make, but the spelling differences mean it's a little harder to read the instructions.”
Jung used the herpes virus to draw inspiration on how to trick the body's cells into responding better to mRNA COVID-19 vaccines. His previous work determined that the herpes virus had developed a tool called a "trans-inducer" to avoid loss of efficiency.
Jung's lab partnered with Dr. Kun Li to create and test alterations of the COVID-19 mRNA vaccine in mice. According to Cleveland Clinic, they found that adding the "efficiency element" from the herpes virus to the COVID-19 mRNA vaccine greatly improved the immune response and protected against lethal levels of infection in preclinical trials. Jung said this protection was good for up to 20 weeks following vaccination.
"We generated the SARS-CoV-2 spike mRNA with the herpes virus glycoprotein coding usage system. Then there is a translator. Herpes virus has a translator — we call that a transducer. We put [them] together, then when you print the human cell, they produce a higher amount of spike protein," Jung said.
Jung noted these modifications to the mRNA COVID-19 vaccine could potentially be applied to other vaccines, like the new Respiratory Syncytial Virus vaccine, but research has a long way to go. His lab is currently applying the same knowledge to other vaccines, like those for Zika virus, so that his research has additional examples before the next stage.
He also said his team isn't sure if these new modifications to the mRNA COVID-19 vaccine would reduce the frequency of booster shots required to keep them updated.
