Introducing a New SARS-CoV-2 Vaccine Candidate

The new vaccine candidate takes advantage of the long and successful history of the measles vaccine.

A team of researchers from The Ohio State University and Nationwide Children’s have built a novel vaccine candidate against SARS-CoV-2. The candidate, published in Proceedings of the National Academy of Sciences (PNAS), used the measles vaccine as a vector to deliver the SARS-CoV-2 spike protein.

“The measles vaccine is one of the best studied and safest vaccines we have. It’s been used in children since the 1960s,” says Jianrong Li, DVM, PhD, senior author of the study and professor of virology in The Ohio State University Department of Veterinary Biosciences. “It is also easy and inexpensive to manufacture, store and distribute.”

“Now we have a vaccine that can protect against measles and COVID-19 at the same time,” adds Stefan Niewiesk, DVM, PhD Diplomate ECLAM, Ohio State professor of veterinary biosciences. “We’re thinking about not just adults but also children.”

Dr. Li and his team—which includes Dr. Niewiesk, Mijia Lu, PhD, a postdoctoral researcher in Dr. Li’s lab and study first author, and Mark Peeples, PhD, principal investigator in the Center for Vaccines and Immunity at Nationwide Children’s and professor of pediatrics at Ohio State—developed the vaccine using a live attenuated measles virus and a stabilized prefusion version of the SARS-CoV-2 spike protein inserted into a “sweet spot” in the measles vaccine genome.

The prefusion version of the protein is the form it has before it fuses with a cell.

“We know from our work studying respiratory syncytial virus, RSV, that the prefusion form, the functional form, of the protein always induces a better immune response than the spent, postfusion version,” says Dr. Peeples.

The team capitalized on the work of a team that published a stabilized prefusion form of the SARS-CoV-2 spike protein in Science in March 2020. This stabilized form of the spike is also used as the basis for the Moderna mRNA vaccine, says Dr. Peeples.

While experts currently don’t know if people will need booster or regular updates to the currently approved SARS-CoV-2 vaccines — similar to the current flu shot schedule — Dr. Li and the team have their sights set on long-term immunity.

“The measles vaccine protects longer than any other vaccine, lifelong for many people, and it is our hope that this will be true for the measles-vectored SARS-CoV-2 vaccine, also” says Dr. Li.

But the longevity of the measles vaccine raised an important question that the researchers had to answer: Will the vaccine work on individuals who are already immune to measles?

The team used a series of experiments in animal models to confirm that the measles-vectored SARS-CoV-2 vaccine did in fact stimulate an antibody response and provide protection against disease even in animals who had been previously immunized to measles.

In one of the experiments published in the PNAS paper, the vaccine induced more antibodies than are found in the blood of people who had been infected with SASR-CoV-2, says Dr. Li. Notably, the majority of the antibodies produced in response to the vaccine are neutralizing antibodies, which offer protection of the lungs and prevent individuals from passing on the virus to others.

But antibodies aren’t the only part of the immune system that are activated and provide immunity. T cells act as the body’s archivists, creating memory cells to specific viral proteins. These T cells can be called into action if the antigen is presented months or years after the initial exposure.

“The nature of vaccine-induced T cells determines its safety, durability and efficacy of preventing viral infection and disease in the future,” explains Amit Kapoor, PhD, principal investigator in the Center for Vaccines and Immunity at Nationwide Children’s and co-author of the study.  “Because a Th2 (T helper 2) biased vaccine response can have adverse health consequences during coronavirus infection, we analyzed the orientation of T cells induced by measles vaccine, and determined that this vaccine induced a Th1 (T helper 1) biased response. This bodes well for the vaccine’s safety and efficacy.”

While the team is enthusiastic about the future of the vaccine, they also say that they have more work to do.

“We want to get into human trials because of the benefit to humanity,” says Dr. Peeples. “But we also want to have the best version of the vaccine we’ve created when we do. We know we can improve this one based on the ongoing experiments our team is conducting. And we’re committed to doing that before we take the next step.”

The vaccine candidate has been licensed to Biological E. Limited (BE), a Hyderabad-based Pharmaceuticals & Biologics Company founded in 1953 that was the first private sector biological products company in India and the first pharmaceutical company in Southern India. BE develops, manufactures, and supplies vaccines and therapeutics to more than 100 countries. Its therapeutic products are sold in India and the United States.

This study was supported by startup funds and bridge funds from Ohio State’s 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.

Reference:

Lu M, Dravid P, Zhang Y, Trivedi S, Li A, Harder O, Kc M, Chaiwatpongsakorn S, Zani A, Kenney A, Zeng C, Cai C, Ye C, Liang X, Shimamura M, Liu SL, Mejias A, Ramilo O, Boyaka PN, Qiu J, Martinez-Sobrido L, Yount JS, Peeples ME, Kapoor A, Niewiesk S, Li J. A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike. Proceedings of the National Academy of Science U.S.A. 2021 Mar 23;118(12):e2026153118.

Image credits: Adobe Stock (header); Nationwide Children’s (Peeples, Kapoor); Ohio State (Niewiesk, Li)