Building on the success story of the measles vaccine to protect against SARS-CoV-2

A new vaccine candidate for SARS-CoV-2, developed by walking the body’s gene for a key protein while locked in a measles vaccine, has been shown to produce a strong immune response and prevent infection of the measles. SARS-CoV-2 and lung disease in multiple animal studies.

Scientists attribute the efficacy of the candidate vaccine to strategic antigen production. to boost immunity– Using a specific fragment of the coronavirus spike protein gene and inserting it at an optimal point in the measles vaccine genome to drive the activation or expression of the gene that produces the protein.

Even with several vaccines already on the market, the researchers say this candidate may have advantages worth exploring, especially related to the established 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, lead author of the study and professor of virology in the University’s Department of Veterinary Biosciences. Ohio State.

“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 huge advantage, because at this point we don’t know how long protection will last with any vaccine platform. “

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 is published online today (March 9, 2021) in the journal procedures of the National Academy of Sciences.

The coronavirus that causes COVID-19 uses the spike protein on its surface to bind to its 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 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 his colleagues Mijia lu, postdoctoral researcher in Li’s lab and first author of the paper, and co-authors Stefan niewiesk, Ohio State Professor of Veterinary Biosciences, and Mark Peeples, Ohio State Professor of Pediatrics and Investigator 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 “prefusion” version of the protein – the form the protein is in before infecting a cell.

The scientists inserted the pre-fusion spike protein gene containing the manufacturing instructions into a segment of the measles vaccine genome to generate high expression of the protein, reasoning that the more SARS-CoV- spike protein 2 occurs, the better the immune response.

The team tested the candidate vaccine in various animal models to measure its efficacy 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 status as a coronavirus vaccine vehicle useless. To allay those concerns, the researchers gave cotton rats a measles vaccine and showed that a second immunization with the measles-based SARS-CoV-2 vaccine candidate could induce a strong neutralizing antibody response to the coronavirus.

The genetically engineered mice produced helper T cells, a type of white blood cell, in response to the vaccine, another important way the body fights infections and, in particular, serious diseases.

“The targeting of helper T cells induced by a vaccine is an important predictor of protection, and this vaccine primarily induces Th1 cells, improving the safety and efficacy of the vaccine,” said co-author Amit Kapoor, associate professor of pediatrics at Ohio. State and researcher at Nationwide Children’s Hospital.

Golden Syrian hamsters, which are susceptible to COVID-19, received the vaccine and were then injected with the coronavirus. The vaccinated hamsters were protected from lung infection and other symptoms of illness indicated by weight loss.

“When we looked at the amount of neutralizing antibodies induced in the hamster, it was actually higher than in people who had been infected with COVID, suggesting that the vaccine may be better than SARS-CoV-2 infection in inducing protective immunity. . That was our goal, ”Peeples said.

Researchers trust the platform not only because the measles vaccine is safe, effective, and affordable to produce, but because a number of experimental measles-based vaccines are being developed against other viruses. 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 much to learn about which ones are the safest and most effective for specific populations, such as children and pregnant women, and which vaccines are suitable. the most economical to produce.

“We can make vaccines much faster now than in the past. But if we had to do it the traditional way this time, we would not have a vaccine to protect us in this short period of time, “said Niewiesk. “The mRNA vaccines that are used now were made in record time. And they protect against disease and are safe. Although not as fast, we were able to make 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 protect for a long time, that is easy to make and cheap seems like a good idea. “

This study was supported by seed funds and bridging funds from the Department of Veterinary Biosciences and the Ohio State College of Veterinary Medicine, an initial grant from the National 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 from 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 the Ohio State School of Medicine.

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