There are historic advances to applaud in the fight against COVID-19. Vaccines are rolling out, and people are getting shots at a rate of more than 2 million a day. The vaccines cleared for Emergency Use Authorization by the Food and Drug Administration are protecting people from serious disease, and it appears they can quell contagion in communities. Vaccination is beginning to extinguish the raging fire of the pandemic.
At the same time, the work of the global medical and scientific community has just begun. We need additional discoveries to deliver the next generation of solutions that can stand up to the virus and its evolving strains in a lasting way.
Like many other scientists in the COVID fight right now, I’m a veteran of the war on HIV. I was a medical student when the AIDS epidemic hit, and it quickly became the focus of my research at Columbia University. My work on HIV led me to discover the CD40 ligand, the molecular basis of T cell help. This science is now being used to identify and measure SARS-CoV-2-specific T cells that combat COVID-19 and clear the virus.
A federally coordinated effort comparable to the Manhattan Project has produced the first-generation vaccines in the United States, and lives are being saved. The Moderna and Pfizer-BioNTech mRNA vaccines and the Johnson & Johnson Ad26 adenovirus-based vaccine that prevent severe COVID-19 symptoms represent an impressive step forward.
All three solutions use a technology developed by National Institute of Allergy and Infectious Diseases scientists for stabilizing the spike protein — heroic work done well before COVID-19 emerged. Additionally, federal agencies, venture capitalists, and philanthropic groups such as the Gates Foundation supported pre-COVID advances in mRNA capping research, lipid encapsulation technology, and the development of Ad26. The lesson here is that we must think ahead and push for new innovations before we come face to face with the next menacing variant or strain.
The COVID-19 vaccine frontier remains largely uncharted, and there are unanswered questions about the EUA vaccines. We don’t know the durability of the protection, whether it’s for a matter of months or more, nor are there definitive findings on forward transmission. The impact of rapidly emerging CoV-2 variant strains on vaccine efficacy also remains largely unknown. Whether the new vaccinology can be used to prevent disease in children leaves us with important open questions as well.
As new COVID-19 strains quickly mutate and share DNA, they pose a constant threat to the efficacy of vaccines on the market today. They will continue to undermine public health until we find a solution that elicits a much more powerful human immune response. Because SARS-CoV-2 is likely to be endemic, what we need for the long run are vaccines that allow us to coexist with COVID-19, just as we do with measles, mumps, and rubella.
My colleagues and I believe the best way to accomplish this is to induce T-cell immunity with a live virus vaccine. A live vaccine wiped out smallpox, the only disease ever eradicated. That’s because live virus vaccines such as horsepox and closely related vaccinia provide proven, durable viral immunity and block forward transmission. We know that an attenuated live virus vaccine invokes a T-cell response that kills infected host cells and marshals other immune cells to defend strongly against infection. This kind of robust immunity has the potential to last years, decades, or even a lifetime. In short, the cornerstone of enduring viral protection is T-cell immunity.
There is good reason to think that live virus vaccines able to stimulate T cells will stand up to the new highly infectious COVID-19 strains currently spreading at disturbing rates. We have compelling data from immunized non-human primates and have observed that the T cell epitopes are more conserved than antibody epitopes. In addition, most of the live-virus candidates in various stages of development would be administered in a single dose, can be scaled for mass production, and would not require a challenging cold chain.
While the tide is turning, we haven’t won the war yet. Until we see a powerful vaccine breakthrough that defeats the virus, more transmissible and lethal strains will continue to surface and thrive.
With the hope of a broadly adopted and durable vaccine, it would be short-sighted to let up on investing in vaccine candidates that generate long-term T cell immunity and prevent forward transmission. While it takes time to successfully develop this kind of vaccine and demonstrate efficacy in clinical trials, the results could be life changing and blunt the impact of COVID-19 on future generations.
This critical work requires resources that could be funded through targeted private-public partnerships as well as congressional appropriations. The kind of federal support we saw in 2020 for vaccine development, bureaucratic streamlining, and manufacturing must continue until we all can be safe from the coronavirus.
Great achievements by brilliant scientists have delivered us to a pivotal moment in the battle against COVID-19, and this is no time for complacency. We must be relentless until we finally have a vaccine that stops transmission for good, offers enduring protection, and restores public health. That will be victory.
Seth Lederman is a physician and scientist. He is CEO of Tonix Pharmaceuticals.
