A new SARS-CoV-2 vaccine candidate, developed by providing a gene for a key protein to the body while involved in a measles vaccine, has been shown to produce a strong immune response and prevent SARS-CoV- infection. 2 and lung disease in multiple animal studies.
Scientists attribute the effectiveness of the candidate vaccine to the strategic production of the antigen to stimulate immunity: using a specific fragment of the coronavirus spike protein gene and inserting it at an ideal point in the measles vaccine genome to increase the activation, or expression, of the gene that produces the protein.
Even with several vaccines already on the market, the researchers say that this candidate may have advantages that are worth exploring – especially related to the proven safety, durability and high efficacy profile of 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, senior author of the study and professor of virology in the Department of Veterinary Biosciences at Ohio State University.
“We also know that the measles vaccine can provide 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 now we don’t know how long the protection will last with any vaccine platforms. “
The Ohio State Innovation Foundation has exclusively licensed the technology to Biological E. Limited (BE), a pharmaceutical and vaccine company based in Hyderabad, India.
The research was published online today (March 9, 2021) in the journal Proceedings of the National Academy of Sciences.
The coronavirus that causes COVID-19 uses the spike 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 starts the production of antibodies that recognize the new protein as foreign, training the immune system to attack and neutralize the spike protein if SARS-CoV-2 ever enters the body.
Li created the COVID-19 vaccine using a live attenuated measles virus as a vehicle with colleagues Mijia Lu, a postdoctoral researcher in Li’s laboratory and first author on the article, and co-authors Stefan Niewiesk, Ohio veterinary bioscience professor and Mark Peeples, Ohio state pediatric 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 in a stabilized “pre-fusion” version of the protein – the form the protein takes before infecting a cell.
The scientists inserted the gene for the pre-fusion peak protein containing manufacturing instructions into a segment of the measles vaccine genome to generate high protein expression, arguing that the more SARS-CoV-2 peak protein produced, the better the immune response.
The team tested the candidate vaccine on several animal models to assess its effectiveness and found that the vaccine induced high levels of neutralizing antibodies against SARS-CoV-2 in all animals.
Some might think that most humans’ immunity to measles, thanks to decades of widespread vaccination, would render their status as a coronavirus vaccine vehicle useless. To allay these concerns, the researchers gave cotton mice a measles vaccine and showed that a second immunization with the measles-based SARS-CoV-2 vaccine 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 for the body to fight infections and, in particular, serious illnesses.
“The orientation of helper T cells induced by a vaccine is an important predictor of protection, and this vaccine primarily induces Th1 cells, which increases the safety and efficacy of the vaccine,” said co-author Amit Kapoor, associate professor of pediatrics in Ohio State and researcher at Nationwide Children’s Hospital.
Golden Syrian hamsters, susceptible to contracting 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 looked at the amount of neutralizing antibodies induced in the hamster, it was actually higher than in people infected with COVID, suggesting that the vaccine may be better than SARS-CoV-2 infection in inducing protective immunity. That was our goal, ”said Peeples.
Researchers trust the platform not only because the measles vaccine is safe, effective and affordable to produce, but because several experimental measles vaccines against other viruses are in development. A vaccine against the mosquito-borne chikungunya virus has been shown to be safe, well tolerated and good at eliciting an immune response in a Phase 2 clinical trial.
And even with a variety of COVID-19 vaccines now available in the United States and other countries, there is still a lot to learn about which are the safest and most effective for specific populations, such as children and pregnant women, and which vaccines are the most economical to produce.
“We can make vaccines much more quickly now than in the past. But if we had to do it the traditional way this time, we wouldn’t have a vaccine protecting us in this short time, ”said Niewiesk. “The mRNA vaccines in use have now been made in record time. And they protect against disease and are safe. Although it is not that fast, we were able to make this vaccine much more quickly 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 protect for a long time, is easy to manufacture and inexpensive seems like a good idea. “
This study was funded by startup funds and intermediary funds from the Department of Veterinary Biosciences and Ohio State College of Veterinary Medicine, a seed grant from the Nationwide Children’s Hospital and grants from the National Institutes of Health.
Other 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 from the Research Institute of the Nationwide Children’s Hospital; and Ashley Zani, Adam Kenney, Chuanxi Cai and Jacob Yount of the Department of Microbial Infection and Immunity at Ohio State School of Medicine.
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