A new SARS-CoV-2 candidate vaccine, developed by donating a key protein gene to the body while wrapped in a measles vaccine, has been shown to show a strong immune response and prevent SARS infection. -CoV-2 and lung disease in multiple animal studies.
Scientists attribute the efficacy of the vaccine candidate to strategic antigen production to stimulate immunity: using a specific fragment of the coronavirus ear protein gene and inserting it into a sweet spot in the measles vaccine genome to increase activation or expression of the gene that makes the protein.
Even with several vaccines on the market, researchers claim that this candidate may have advantages worth exploring, especially related to the safety, durability, and high efficacy profile established by the measles vaccine.
“The measles vaccine has been used in children since the 1960s and has a long history of safety for children and adults,” said Jianrong Li, lead author of the study and professor of virology in the Department of Veterinary Biosciences. of Ohio State University.
“We also know that the measles vaccine can produce long-term protection. The hope is that with the antigen inside it can produce long-term protection against SARS-CoV-2. That would be a great advantage, because right now we don’t know how long the protection will last with any vaccine platform ”.
The Ohio State Innovation Foundation has licensed the technology exclusively to Biological E. Limited (BE), a pharmaceutical and vaccine company based in Hyderabad, India.
The research is published online today (March 9, 2021) in the journal Proceedings of the National Academy of Sciences.
The coronavirus that causes COVID-19 uses the ear protein on its surface to bind to target cells in the nose and lungs, where it makes copies of itself and releases them to infect other cells. Like all vaccines, this candidate initiates the production of antibodies that recognize the new protein as foreign, training the immune system to attack and neutralize the tip protein if SARS-CoV-2 ever enters the body.
He created the COVID-19 vaccine using a live attenuated measles virus as a vehicle with colleagues. Mijia Lu, postdoctoral researcher in Li’s laboratory and first author of the work and co-authors Stefan Niewiesk, Ohio State Veterinary Biosciences Professor and Mark Peeples, Ohio State Pediatrics Professor and Researcher at Nationwide Children’s Hospital in Columbus.
For this work, the researchers tested seven versions of the spike protein to find the most effective antigen. They landed on a stabilized “protein” version of the protein, the way the protein is found before it infects a cell.
The scientists inserted the prefusion ear protein gene that contains manufacturing instructions into a segment of the measles vaccine genome to generate high protein expression, arguing that the more SARS-CoV-2 ear protein is produced. , the better the immune response.
The team tested the candidate vaccine in several animal models to evaluate its effectiveness and found that the vaccine induced high levels of neutralizing antibodies against SARS-CoV-2 in all animals.
Some may think that the immunity of most humans to measles, thanks to decades of widespread vaccination, would render their condition as a vehicle against the coronavirus vaccine useless. To allay these concerns, the researchers administered a measles vaccine to cotton rats and showed that a second vaccination with the SARS-CoV-2 measles vaccine-based candidate could induce a strong neutralizing antibody response to the coronavirus. .
Genetically modified mice produced helper T cells, a type of white blood cell, in response to the vaccine, another important way to fight infections and, most importantly, serious diseases.
“The targeting of helper T cells induced by a vaccine is an important predictor of protection, and this vaccine mainly induces Th1 cells, which improves the safety and efficacy of the vaccine,” said the co-author Amit Kapoor, associate professor of pediatrics in Ohio. State and researcher at Nationwide Children’s Hospital.
Syrian golden hamsters, likely to contract COVID-19, received the vaccine and were injected with the coronavirus. Vaccinated hamsters were protected against lung infection and other symptoms of disease indicated by weight loss.
“When we examined the amount of neutralizing antibodies induced in the hamster, it was actually higher than that of people who had been infected with COVID, suggesting that the vaccine might be better than SARS-CoV-2 infection to induce the protective immunity. That was our goal, “Peeples said.
Researchers rely on the platform not only because the measles vaccine is safe, effective, and affordable to produce, but because several experimental measles-based vaccines against other viruses are being developed. In a phase 2 clinical trial, a mosquito-borne chikungunya virus vaccine has been shown to be safe, well tolerated, and capable of eliciting an immune response.
And even with a wide variety of COVID-19 vaccines available in the United States and other countries, much remains to be learned about which are the safest and most effective for specific populations, such as children and pregnant women, and which vaccines are the cheapest to produce.
“We can get vaccinated much faster now than in the past. But if we had to do it the traditional way this time, we wouldn’t have a vaccine that would protect us in that short period of time, “Niewiesk said. record time.And they protect against disease and are safe.Although it is not that fast, we have been able to manufacture this vaccine much faster than the original measles vaccine.
“We still don’t know how long mRNA vaccines will protect or how much they will cost. Meanwhile, an alternative vaccine that should be protected for a long time is easy to manufacture and economical seems like a good idea.”
This study was supported by start-up funds and bridge funds from the Ohio State Department of Veterinary Biosciences and the College of Veterinary Medicine, an initial grant from Nationwide Children’s Hospital and grants from the National Institutes of Health. .
Additional co-authors are Yuexiu Zhang, Anzhong Li, Olivia Harder, Cong Zeng, Xueya Liang, Shan-Lu Liu, and Prosper Boyaka of the Ohio State Department of Veterinary Biosciences; Piyush Dravid, Sheetal Trivedi, Mahesh KC, Supranee Chaiwatpongsakorn, Masako Shimamura, Asuncion Mejias and Octavio Ramilo of the Research Institute of the National Children’s Hospital; and Ashley Zani, Adam Kenney, Chuanxi Cai, and Jacob Yount, of the Department of Infection and Microbial Immunity at Ohio State College of Medicine.
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