A new SARS-CoV-2 vaccine candidate, developed by giving a key protein gene into the body while wrapped in a measles vaccine, has been shown to provide a strong immune response and prevent SARS CoV-2 infection and lung disease occur. multiple animal studies.
Scientists attribute the effectiveness of the vaccine candidate to strategic production of the antigen stimulate immunity: use a specific fragment of the coronavirus protein gene, and place it in a sweet spot in the genome of the measles vaccine to promote the activation or expression of the gene that makes the protein.
Even with several vaccinations already on the market, researchers say that this candidate may have the benefits that are worth investigating – especially with regard to the established safety, durability and efficacy profile of measles.
“The measles vaccine has been used in children since the 1960s, and it has a long history of safety for children and adults,” said Jianrong Li, senior author of the study and a professor of virology at the Ohio State University Department. of Veterinary Biosciences said.
‘We also know that the measles vaccine can provide long-term protection. The hope is that it can deliver with the antigen within long-term protection against SARS-CoV-2. This would be a huge advantage, as we do not know at the moment how long protection with any vaccine platforms will last. ”
The Ohio State Innovation Foundation licensed the technology exclusively to Biological E. Limited (BE), a vaccine and pharmaceutical company located in Hyderabad, India.
The research will be published online today (9 March 2021) in the journal Proceedings of the National Academy of Sciences.
The coronavirus that causes COVID-19 uses the vein 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. As with all vaccines, this candidate begins the production of antibodies that recognize the new protein as foreign, training the immune system to attack and neutralize the peak 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 of the paper, and co-authors Stefan Niewiesk, Ohio Professor of Veterinary Biosciences, and Mark Peeples, Professor of Pediatrics at Ohio State and a researcher at Nationwide Children’s Hospital in Columbus.
For this work, the researchers tested seven versions of the ear protein to find the most effective antigen. They ended up on a stabilized “prefusion” version of the protein – the form the protein is in before it infects a cell.
The scientists inserted the prefusion vein protein gene containing manufacturing instructions into a segment of the genome called measles vaccine to generate a high expression of the protein, arguing that the more SARS-CoV-2 ear protein produced, the better the immune response.
The team tested the vaccine candidate in different animal models to determine its efficacy, and found that the vaccine causes high levels of neutralizing antibodies against SARS-CoV-2 in all animals.
Some may believe that the immunity of most people to measles, thanks to decades of widespread vaccination, would render its status as a coronavirus vaccine useless. To suppress the problems, researchers gave cotton rats a vaccine against measles and showed that a second vaccine with the SARS-CoV-2 vaccine candidate against measles could cause a strong neutralizing antibody response to the coronavirus.
Genetically modified mice have produced helper T cells – a type of white blood cell – in response to the vaccine, another important way the body fights infection, and especially serious diseases.
“The orientation of T helper cells induced by a vaccine is an important predictor of protection, and this vaccine mainly causes Th1 cells, which increases the safety and efficacy of the vaccine,” said co-author Amit Kapoor, associate professor of pediatrics at Ohio, said. State and a researcher at Nationwide Children’s Hospital.
Golden Syrian hamsters, which are susceptible to contracting COVID-19, received the vaccine and were subsequently injected with the coronavirus. The vaccinated hamsters are protected against lung infection and other disease symptoms indicated by weight loss.
‘When we looked at the amount of neutralizing antibodies induced in the hamster, it was actually higher than that of people infected with COVID, suggesting that the vaccine may be better than SARS-CoV-2 infection to boost protective immunity effected. That was our goal, “said Peeples.
The researchers rely not only on the platform because the measles vaccine is safe, effective and affordable to produce, but because several experimental measles vaccines are being developed against other viruses. A vaccine against chikungunya virus, spread by mosquitoes, has been shown to be safe, well tolerated and can elicit 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 what is safest and most effective for specific populations, such as children and pregnant women, and which vaccines is the most economical to produce.
‘We can make vaccinations much faster now than in the past. But if we had to do it in the traditional way this time, we would not have a vaccine that protects us within this short time, ”Niewiesk said. ‘The mRNA vaccines currently in use were made in record time. And they protect against disease and are safe. Although it was not so fast, we were able to make this vaccine much faster than the original vaccination against measles.
‘We do not yet know how long the mRNA vaccines will protect or how much it will cost. Meanwhile, an alternative vaccine that is long-lasting, easy to manufacture and inexpensive seems like a good idea. ”
This study was supported by start-up funds and bridge funds from the Department of Veterinary Biosciences in Ohio and the College of Veterinary Medicine, a seed 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 Ohio State Veterinary Biosciences Department; Piyush Dravid, Sheetal Trivedi, Mahesh KC, Supranee Chaiwatpongsakorn, Masako Shimamura, Asuncion Mejias and Octavio Ramilo of the Research Institute at the Nationwide Children’s Hospital; and Ashley Zani, Adam Kenney, Chuanxi Cai and Jacob Yount of the Department of Microbial Infection and Immunity at the Ohio College of Medicine.
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