The world is in a race to develop vaccines against the novel coronavirus SARS-CoV-2 and the disease it causes, COVID-19. We are determined to defeat this disease, which continues to infect millions of people and cause death and suffering around the world. Given the urgent crisis, it’s clear that a vaccine cannot be developed soon enough to help stem the pandemic. With the goal of accomplishing what in normal times would have been deemed impossible, we are engaging collaboratively with regulatory authorities to adapt traditional vaccine research and development to meet this unprecedented challenge.
With our partner BioNTech, a German biotech company, we are developing not one but at least four different vaccine candidates all at once. We began testing the vaccine in Germany on April 23. This week, we’re starting to test our mRNA vaccine candidates in a U.S. trial — only six weeks after kicking off our COVID-19 partnership.
Never in my over 25 years of developing vaccines have I seen a clinical trial launched at this speed. Usually, it takes years of dedicated research to get to this point. This record milestone is a testament to the innovation and collaboration among researchers and colleagues from two very different organizations and cultures, unprecedented access to advice and support from regulatory agencies and other government agencies, and the willingness of companies to go above and beyond what is “normal” for them.
Our approach is based on the same technology that we are developing in another partnership with BioNTech — an mRNA seasonal influenza vaccine, which has not yet entered clinical studies. If successful, that vaccine could potentially transform the yearly “scramble” of producing a flu vaccine by increasing the speed of development and coverage of circulating strains. We saw the opportunity to pursue a collaboration with BioNTech on the same platform technology for COVID-19, which could potentially help us develop a vaccine faster than using traditional approaches.
Unlike many conventional vaccines — which usually take months to years of research because they entail first developing biological cell, virus or bacterial production processes — mRNA vaccines are fully synthetic, well characterized and use nearly identical processes for purification. If the vaccine platform is proven to work, it could allow us to quickly adapt the platform to other pathogens by exchanging the small portion of the SARS-CoV-2 genetic code for that of another pathogen.
The anticipated virtues of mRNA
In most conventional viral vaccines used today, weakened or killed forms of a virus, or protein components of the pathogen known as antigens, are administered to a person. The immune system then recognizes these foreign virus components and unleashes a multipronged defense: special immune cells to kill infected cells and specific antibodies to prevent the virus from infecting our cells. Then, if a vaccinated person encounters the virus in the future, their immune system already knows how to recognize, respond and defeat it before they become sick.
The mRNA vaccine technology does not require the lengthy production of weakened or killed viruses or the viral antigen. Instead, mRNA, a set of genetic instructions coding for viral antigens, is injected into the body. Once inside cells, these instructions guide the cell’s machinery to produce the antigens, which can then teach the immune system how to recognize and fight off a future virus attack. In addition, RNA platforms can also “help” the immune system mount a stronger response to an antigen than that induced by the antigen alone. The genetic material RNA can be seen by the immune system as “viral.” That launches a potent arm of the immune system called innate immunity, which recognizes patterns of common pathogens such as viruses and bacteria and increases the potency of the vaccine.
Clinical trials at pandemic speed
Vaccine clinical trials are typically run with only one vaccine candidate in three separate phases, moving from small safety and immunogenicity studies then scaling up to large efficacy trials that usually involve tens of thousands of participants. It’s a deliberative and sequential process that can take many years.
Due to the urgency of the pandemic, well-established clinical development paths would take too long for us. To shorten the time from preclinical to clinical evaluation, we are using a unique approach to test at least four different RNA vaccine candidates in parallel in a smaller number of clinical trial participants.
The ongoing U.S. phase 1/2 study uses a new trial design that maximizes development speed while ensuring safety by quickly eliminating suboptimal vaccine candidates for the benefit of the “winner” in the race. Instead of using sequential individual trials, we plan to adapt the same phase 1/2 trial in real time and based on continuous data collection to select the final vaccine candidate, ensure safety and tolerability and collect functional immunogenicity data to inform the seamless transition into the clinical efficacy stage of the study. Given this design, we are shaving many years from the vaccine development timeline, and assuming success, we’ll potentially be able to roll out a promising vaccine candidate as early as fall 2020.
Early vaccine clinical trials are typically done exclusively in younger populations first and then tested in older populations. We are also changing this model: After determining the safety of each candidate’s dose level in younger populations, we will then immediately test that dose level in older adults, so that necessary safety and immunogenicity data for the population most vulnerable to COVID-19 are available almost at the same time to begin the efficacy stage of the trial.
The war against the virus
The other critical aspect of creating a successful vaccine is ensuring that we can manufacture and distribute hundreds of millions of doses. Again we have changed the typical development approach. Under normal circumstances, the investment of many hundreds of millions to billions of dollars is needed to build vaccine production capacity. These investments occur only after a vaccine candidate has proven itself to be safe and immunogenic.
Today we are compressing a process that usually takes years to one that may take only several months, with huge upfront investments of capital and resources before we have clinical evidence that the vaccine candidate may be successful. To that end, we are working together with BioNTech and Pfizer’s manufacturing teams to quickly scale up infrastructure and try to eliminate any potential bottlenecks in sourcing the materials needed to produce hundreds of millions of vaccine doses in record time.
I’ve dedicated my scientific career to creating and developing vaccines so that vulnerable populations all over the globe can be protected from disease and death. I have witnessed firsthand the tremendous power of vaccines to change lives and help ensure that children have a fighting chance to grow up healthy.
Vaccine R&D has always been challenging, but there is normally sufficient time to solve scientific problems during development. The current crisis has turned our world upside down as time is the one thing we do not have. We are all energized and inspired to offer potential solutions with an unprecedented sense of urgency to make what seemed impossible only a couple of months ago now possible. The ongoing experience has fortified my belief in the power of science, researchers, health care professionals and others working closely to address the pandemic. This virus is our enemy. And we need to do everything in our power to win the war against it, not tomorrow, but today.
By KATHRIN U. JANSEN, SENIOR VICE PRESIDENT AND HEAD OF VACCINE RESEARCH AND DEVELOPMENT AT PFIZER.
Originally published on Politico.com
Published on 4th June