Leverage the success history of the measles vaccine to protect against SARS-CoV-2

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

Scientists attribute the effectiveness of the vaccine candidate to the strategic production of the antigen to stimulate immunity: using a specific fragment of the coronavirus protein gene and inserting it into a sweet spot in the measles vaccine genome to stimulate activation or expression of the protein-producing gene.

Even with several vaccines already available on the market, researchers say this candidate could have benefits worth exploring – especially in terms of the established safety, durability and 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 at the State University Department of Veterinary Biosciences. Ohio.

“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. This would be a great advantage, because at the moment we do not know how long the protection will last with any vaccination platform. ”

The Ohio State Innovation Foundation has licensed the technology exclusively to Biological E. Limited (BE), a pharmaceutical and vaccine company in Hyderabad, India.

The research is published online today (March 9, 2021) in the journal The works 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 on its own and releases them to infect other cells. Like all vaccines, this candidate initiates the production of antibodies that recognize the new protein as foreign, causing the immune system to attack and neutralize the spike protein if SARS-CoV-2 ever enters the body.

Li created COVID-19 vaccine using a live attenuated measles virus as a vehicle with colleagues Mijia Lu, a postdoctoral researcher in Li’s laboratory and the first author of the paper and co-authors Stefan Niewiesk, Ohio State Professor of Veterinary Biosciences and Mark Peeples, Professor of Pediatrics at Ohio State 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 “prefusion” version of the protein – the form in which the protein is before it infects a cell.

Scientists have inserted the prefusion protein gene that contains manufacturing instructions into a segment of the measles vaccine genome to generate high protein expression, arguing that as many SARS-CoV-2 proteins are produced, with both the immune response is better.

The team tested the vaccine candidate on 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 might think that the immunity of most people to measles, due to decades of widespread vaccination, would make it useless as a vehicle for the coronavirus vaccine. To alleviate these concerns, the researchers gave the cotton rats a measles vaccine and showed that a second immunization with the measles vaccine based on the SARS-CoV-2 vaccine could induce a strong neutralizing antibody response to coronavirus.

Genetically modified mice have produced helper T cells – a type of white blood cell – in response to the vaccine, another important way in which the body fights infections and, in particular, severe diseases.

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

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

“When we looked at the amount of neutralizing antibody induced in the hamster, it was actually higher than in people who were 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, but also because several experimental measles-based vaccines against other viruses are being developed. A vaccine against the chikungunya virus, spread by mosquitoes, 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 are the safest and most effective for specific populations, such as children and pregnant women, and which are the most economical product vaccines.

“We can make vaccines much faster now than in the past. But if we had to do it traditionally this time, we would not have a vaccine to protect us in this short time, “said Niewiesk. The mRNA vaccines used now have been made in record time. And they protect against disease and are safe. Although not as fast, we managed to make this vaccine much faster than the original measles vaccine.

“We do not yet know how long they will protect mRNA vaccines or how much they will cost. Meanwhile, an alternative vaccine that should be protected for a long time is easy to make and cheap seems like a good idea. ”

This study was supported by start-up funds and bridge funds from the Ohio Department of Veterinary Sciences and the College of Veterinary Medicine, a seed scholarship 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 from the Research Institute at Nationwide Children’s Hospital; and Ashley Zani, Adam Kenney, Chuanxi Cai and Jacob Yount from the Department of Microbial Infections and Immunity at Ohio State’s College of Medicine.

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