A new SARS-CoV-2 vaccine candidate, developed by driving the gene of a key protein in the body while encapsulated in a measles vaccine, has been shown to produce a strong immune response and produce SARS-CoV-2 infection and lung disease occurs in multiple animal studies.
Scientists attribute the effectiveness of the candidate vaccine to the strategic production of the antigen to boost immunity: use a specific fragment of the coronavirus spike protein gene and place it in a proper position in the genome of the measles vaccine to stimulate the activation or expression of the gene that makes the protein.
Even with several vaccines already on the market, researchers say this candidate may have benefits worth investigating – especially in connection with the measles vaccine’s proven safety, durability and high efficacy.
“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 Ohio State University Department of Veterinary Biosciences.
“We also know that the measles vaccine can provide long-term protection. The hope is that, with the antigen in it, it can produce long-lasting protection against SARS-CoV-2. That would be a big advantage because at the moment we don’t know how long the protection will last with a vaccine platform. “
The Ohio State Innovation Foundation has exclusively licensed the technology to Biological E. Limited (BE), a vaccine and pharmaceutical 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 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 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 lab and lead paper author, and co-authors Stefan Niewiesk Ohio State professor of veterinary life sciences and Mark Peeples, professor of pediatrics at Ohio State 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 it infects a cell.
The scientists inserted the prefusion spike protein gene with production instructions into a segment of the measles vaccine genome to generate high expression of the protein, reasoning that the more SARS-CoV-2 spike protein becomes produced, the better the immune response.
The team tested the vaccine candidate in different animal models to measure its effectiveness and found that the vaccine induced high levels of neutralizing antibodies to SARS-CoV-2 in all animals.
Some may think that, thanks to decades of widespread vaccination, most people’s immunity to measles would render the status of a coronavirus vaccine vehicle useless. To address those concerns, researchers gave cotton rats a measles vaccine and showed that a second immunization with the measles-based SARS-CoV-2 vaccine could elicit a strong neutralizing antibody response to the coronavirus.
Genetically modified mice produced T helper cells – a type of white blood cell – in response to the vaccine, another important way the body fights infections, especially serious illness.
“The orientation of T helper cells induced by a vaccine is an important predictor of protection, and this vaccine mainly induces Th1 cells, enhancing the safety and efficacy of the vaccine,” said study co-author Amit Kapoor, associate professor of pediatrics in Ohio. . State and an investigator at Nationwide Children’s Hospital.
Golden Syrian hamsters, susceptible to COVID-19, were given the vaccine and then injected with the coronavirus. The vaccinated hamsters were protected from 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 even higher than in humans 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.
The researchers are confident in the platform not only because the measles vaccine is safe, effective and affordable to produce, but also because several experimental measles-based vaccines against other viruses are in development. A vaccine against chikungunya virus, spread by mosquitoes, has been shown to be safe, well-tolerated and good at inducing an immune response in a phase 2 clinical study.
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 those are. the most economical to produce.
“We can now make vaccines much faster than in the past. But if we had to do it the traditional way this time, we wouldn’t have a vaccine to protect us in this short amount of time, ”said Niewiesk. “The mRNA vaccines currently in use were created in record time. And they protect against disease and are safe. Although not that fast, we were able to make this vaccine much faster than the original measles vaccine.
“We don’t yet know how long the mRNA vaccines will protect or how much they will cost. In the meantime, an alternative vaccine that provides long-term protection, is easy to manufacture, and is inexpensive seems like a good idea. “
This study was supported by seed and bridging funds from the Ohio State Department of Veterinary Biosciences and College of Veterinary Medicine, a seed grant from Nationwide Children’s Hospital, and grants from the National Institutes of Health.
Other co-authors include 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 Nationwide Children’s Hospital Research Institute; and Ashley Zani, Adam Kenney, Chuanxi Cai, and Jacob Yount of the Microbial Infection and Immunity Division of the Ohio State College of Medicine.
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