COVID-19 is a Sprint AND a Marathon, Requiring New and Better Vaccines
Scientist in the lab/Courtesy Meissa Vaccines
With about 51% of the world at least partially vaccinated against COVID-19 and 23 vaccines authorized for use in various countries, companies are still developing new vaccines for this pandemic and, in some cases, for what may come afterward. While some may wonder about the commercial future of these late-to-the-market solutions, the developers themselves are taking a long view.
“COVID-19 is both a sprint and a marathon,” Martin Moore, Ph.D., CEO of Meissa Vaccines told BioSpace. “It’s obvious COVID-19 isn’t going away, and few would say the Delta variant will be the last variant of interest. If you look at the vaccines in use now, they’re injectable. They prevent serious diseases, but many experts think they won’t block transmission, and that is important for the next generation of vaccines – especially ones that can be administered intranasally.”
Andrey Zarur, Ph.D., co-founder and CEO of GreenLight Biosciences, acknowledged the dire nature of the virus but also stressed another aspect. “We’re a family. We need to care for one another. We have a responsibility to make technological advancements available to everyone,” he said, noting low vaccination rates throughout Africa, Eastern Europe and parts of Asia. It’s also a matter of self-preservation, he explained. “If a large portion of the global population isn’t vaccinated, people get infected. Then the virus mutates and comes back to us.”
The mutating and seemingly persistent nature of the SARS-CoV-2 virus, therefore, calls for new types of vaccines. “The current vaccines are still quite effective against SARS-CoV-2 and current variants,” Dr. Barton Haynes, M.D., director of the Duke Human Vaccine Institute at Duke University School of Medicine, told BioSpace. “However, if variants arise that are completely resistant to the current COVID-19 vaccines, we need to have vaccines ‘on the shelf’ that can be rapidly deployed.
“Moreover,” Haynes continued, “for future pandemic preparedness, we need vaccines that will be effective for any new coronaviruses that arise in humans. We have now had three coronavirus outbreaks during the past 20 years, and one that became a global pandemic. It is probable we will see more coronavirus outbreaks in the future.”
Researchers at Duke, therefore, developed a pancoronavirus vaccine that targets SARS-like coronaviruses, including the current variants of concern. “Now we are moving to other groups of more disparate coronaviruses that are different from the SARS-CoV-2 virus, like the Middle Eastern Respiratory Syndrome (MERS) coronavirus group,” Haynes said. The Duke Human Vaccine Institute was just awarded a three-year, $17.5 million grant from the National Institute of Allergy and Infectious Disease to do that. Duke researchers also are trying to develop a vaccine against the coronaviruses that cause about 30% of the common cold syndromes.
For the current pandemic, Meissa is focused upon a method to block transmission and generate a better immune response against the SARS-CoV-2 virus and its variants by using an intranasal vaccine. The rationale for an intranasal vaccine, Moore explained, is to establish immunity at the site of infection – the nose. Injected vaccines typically induce only serum (IgG) antibodies that circulate in the blood. Intranasal administration also generates mucosal (IgA) antibodies in the nasal cavity.
Just-announced Phase I clinical data from 49 patients shows a strong nasal IgA antibody response in seropositive and seronegative adults after a single dose of MV-014-212. This vaccine is specifically designed to overcome the typical trade-off among live attenuated vaccines and be both highly attenuated (safe) yet confer broad and durable immunity that resembles natural immunity to SARS-CoV-2. “This could be a tool to get back to normal,” Moore said.
“In the big picture, I think our vaccine could be useful as a primary vaccine in children and as an intranasal booster in vaccinated people,” he continued. It offers relatively low manufacturing costs, needleless administration and can be given in a single dose, which makes it particularly beneficial for those unable or unwilling to return to vaccination sites for second injections or for those who have issues with needles.
GreenLight also is taking a newer approach, focusing on improved mRNA vaccines and more scalable manufacturing. As Zarur said of mRNA vaccines, “we’ve learned what works and doesn’t work,” and so have the opportunity to use those learnings to make mRNA vaccines “more stable, more efficient and better in general.” The mRNA vaccine being developed by GreenLight isn’t yet in clinical trials, he said.
In studies involving Syrian golden hamster models, however, the vaccine-induced Th1-biased cell-mediated immune responses. At a single dose, Zarur said, “we’re achieving titers of neutralization antibodies and activation of T cells that are comparable with data from approved vaccines.” GreenLight plans to begin a Phase I clinical study in South Africa in Q1 2022 to determine whether those results will translate to humans.
For any of these vaccines to gain traction in developing regions (where refrigeration may not be reliable), temperature stability will be an issue. GreenLight is working toward that goal with several different lipid nanoparticles, some of which are stable at room or refrigerated temperatures.
If the COVID-19 pandemic becomes endemic, as many suggest it will, vaccinations against the coronavirus are likely to become as regular as vaccinations against the seasonal influenza. In that scenario, vaccine developers will have plenty of time to perfect their vaccines and get them approved, regardless of where they are in development today.