A new SARS-CoV-2 vaccine candidate, developed by giving a key protein’s gene a ride into the body while encased in a measles vaccine, has been shown to produce a strong immune response and prevent SARS-CoV-2 infection and lung disease in multiple animal studies.
Scientists attribute the vaccine candidate’s effectiveness to strategic production of the antigen to stimulate immunity: using a specific snippet of the coronavirus spike protein gene, and inserting it into a sweet spot in the measles vaccine genome to boost activation, or expression, of the gene that makes the protein.
Even with several vaccines already on the market, researchers say this candidate may have advantages worth exploring—especially related to the measles vaccine’s established safety, durability and high-efficacy profile.
“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 a professor of virology in The Ohio State University Department of Veterinary Biosciences.
“We also know the measles vaccine can produce 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 big advantage, because right now we don’t know how long protection will last with any vaccine platforms.”
The Ohio State Innovation Foundation has exclusively licensed the technology to Biological E. Limited (BE), a Hyderabad, India-based vaccine & pharmaceutical company.
The research is published online today 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 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 colleagues Mijia Lu, a postdoctoral researcher in Li’s laboratory and first author on the paper, and co-authors Stefan Niewiesk, Ohio State 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 spike protein to find the most effective antigen. They landed on a stabilized “prefusion” version of the protein—the shape the protein is in before it infects a cell.
The scientists inserted the prefusion spike protein gene containing manufacturing 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 produced, the better the immune response.
The team tested the vaccine candidate in several animal models to gauge its effectiveness, and found that the vaccine induced high levels of neutralizing antibodies against SARS-CoV-2 in all of the animals.
Some may think most humans’ immunity to measles, thanks to decades of widespread vaccination, would render its status as a coronavirus vaccine vehicle useless. To quell those concerns, 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.
Genetically modified mice produced helper T cells – a type of white blood cell – in response to the vaccine, another important way the body fights infection, and severe disease in particular.
“The orientation of T helper cells induced by a vaccine is an important predictor of protection, and this vaccine mainly induces Th1 cells, which enhances the safety and efficacy of the vaccine,” said co-author Amit Kapoor, associate professor of pediatrics at Ohio State and a researcher at Nationwide Children’s Hospital.
Golden Syrian hamsters, which are susceptible to contracting COVID-19, received the vaccine and were then injected with the coronavirus. The vaccinated hamsters were protected from lung infection and other sickness symptoms indicated through weight loss.
“When we looked at the amount of neutralizing antibody induced in the hamster, it was actually higher than from people who had been infected with COVID, suggesting the vaccine may be better than SARS-CoV-2 infection in inducing protective immunity. That was our goal,” Peeples said.
The researchers have confidence in the platform not only because the measles vaccine is safe, effective and affordable to produce, but because several experimental measles-based vaccines against other viruses are in development. A vaccine against chikungunya virus, spread by mosquitos, has been shown to be safe, well-tolerated and good at provoking 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 a lot to learn about which are the safest and most effective for specific populations, such as children and pregnant women, and which vaccines are the most economical to produce.
“We can make vaccines much more quickly now than in the past. But if we had to do it the traditional way this time, we wouldn’t have a vaccine protecting us in this short amount of time,” Niewiesk said. “
The mRNA vaccines in use now were made in record time. And they protect against disease and are safe. Although not quite as fast, we were able to make this vaccine much more quickly 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 should protect for a long time, is easy to manufacture and cheap seems like a good idea.”
- Consortium to be led by the Institut Pasteur and will include Themis and the University of Pittsburgh.
- CEPI to provide initial US$4.9 million for consortium to develop a COVID-19 vaccine candidate based on measles-vector technology.
- Partnership becomes eighth COVID-19 vaccine development project that CEPI has signed since Jan 23, 2020.
OSLO, NORWAY, March 19, 2020 – CEPI, the Coalition for Epidemic Preparedness Innovations, today added an eighth COVID-19 vaccine candidate to its portfolio. CEPI will invest an initial US$4.9 million in a partnering agreement with the Institut Pasteur-led consortium that will include Themis and the University of Pittsburgh to develop a vaccine candidate against COVID-19. This collaboration brings CEPI’s total investment in COVID-19 vaccine R&D to US$29.2 million.
In a first step, CEPI funding will support the preclinical testing, initial manufacture of vaccine materials, and preparatory work for phase 1 studies.
To date, CEPI has provided initial funding to Curevac, Inc., Inovio Pharmaceuticals, Inc., Moderna, Inc., Novavax, Inc., The University of Hong Kong, The University of Oxford, and The University of Queensland to develop COVID-19 vaccine candidates.
This investment is the result of a recent global call for proposals that CEPI issued in early February, which invited funding applications for proven vaccine technology that could be used to rapidly develop a vaccine against the new coronavirus, and most importantly at scale and with the necessary equitable access provisions.
“CEPI was set up to accelerate the development of vaccines against emerging infectious threats like COVID-19. One of the ways we’re doing this is by bridging the gap between public and private sectors to pool resources and expertise to jump start the vaccine development process. I’m pleased that CEPI has been able to help establish and fund this consortium of leading vaccine developers, through our recent call for proposals, to harness this measles vector platform to develop a vaccine against COVID-19. It is clear that an effective vaccine against COVID-19 is crucial if we are to beat this virus. By investing in a range of partners and vaccine technologies, we are giving ourselves the best chance of developing a vaccine that can stop COVID-19 in its tracks. We are calling on the international community to contribute to the fight against COVID-19 by investing in CEPI’s vaccine development programme, and help us deliver a long-term equitable solution to this unprecedented global challenge.”
Dr. Richard Hatchett
Chief Executive Officer, CEPI
“The expertise of the Institut Pasteur (Paris) in emerging infectious diseases is one of the priorities of our Strategic Plan 2019-2023. As part of the COVID-19 Task Force set up in January 2020, after our isolation of the coronavirus strains detected in France, the proprietary measles vector (MV) technology was chosen to develop a vaccine against SARS-CoV-2 leveraging our extensive experience with human measles vector technology and an MV-SARS-CoV-1 candidate. We are delighted to continue our long-lasting collaboration with Themis and CEPI that has already delivered high potential vaccine candidates for Chikungunya, nearing phase 3, and Lassa fever in phase 1, both emerging infectious diseases representing a threat to global health.
Stewart Cole
President of the Institut Pasteur
“Our versatile, plug-and-play manufacturing technology affords us the advantage of accelerating the discovery and development of a vaccine candidate against the highly infectious and potentially pandemic coronavirus. We have demonstrated an excellent immunogenicity, safety and manufacturability profile of the technology in late stage clinical development already and are confident to apply this experience to our COVID-19 vaccine development. We are excited to work with our colleagues from Institut Pasteur and the University of Pittsburgh to contribute to fighting this global health situation as soon as possible.
Erich Tauber
MD, CEO of Themis
“The National Institute of Allergy and Infectious Diseases (NIAID) supported Regional Biocontainment Laboratories (RBL) housed at the Center for Vaccine Research is a state-of-the-art facility for research on Biosafety Level -3 (BSL-3) biodefense and emerging infectious diseases. It is our mandated role to respond rapidly to global outbreaks such as COVID-19; to develop animal models of disease; to use these to test the efficacy of candidate vaccines such as recombinant measles viruses expressing a range of SARS-CoV-2 genes. All of our efforts will be directed to address this rapidly changing public health emergency. We are delighted to be part of this multinational, world-class consortium.
Paul Duprex
Director of the Center for Vaccine Research at the University of Pittsburgh
Measles vector platform
The measles vaccine is used here as a vehicle. Using the measles vaccine virus (also called MV) as a vector, recombinant vaccines can be designed to express antigens from other pathogens (Chikungunya virus, Lassa fever, MERS, HIV, dengue, West Nile, yellow fever, or other emerging diseases). The use of the modified MV as a vehicle for vaccination against these pathogens makes it possible to deliver the antigens directly in the compartments of the immune system capable of inducing a protective memory response.
With its broadly applicable technology platform licensed to Themis, the Institut Pasteur has successfully collaborated for 10 years with Themis. This approach was used to develop a vaccine candidate against SARS, and CEPI has previously partnered with Themis and Institut Pasteur to harness this technology to develop vaccine candidates against Chikungunya, MERS, and Lassa fever.
More information: Mijia Lu et al, A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2026153118
