On Monday, the Nobel Prize in Medicine was bestowed upon two distinguished scientists for their groundbreaking contributions to developing mRNA vaccines against COVID-19.
COVID-19 : Years of Research Laid
As nations geared up for the distribution of these vaccines, The Associated Press conducted an in-depth examination of the remarkable speed at which these life-saving vaccines were created. Below is the original article, which was initially published on December 7, 2020.
How did scientists manage to expedite the development of COVID-19 vaccines without compromising safety?
A significant advantage played a crucial role – more than a decade of covert research that had already positioned new vaccine technology for a pivotal test, coinciding perfectly with the onset of the coronavirus outbreak.
The rapid pace at which these vaccines were developed is a testament to the years of groundwork that preceded them,” emphasized Dr. Anthony Fauci, the leading infectious disease expert in the United States, in an interview with The Associated Press COVID-19.
The remarkable achievement of developing vaccines and obtaining robust study results in less than a year following the emergence of an entirely new disease is nothing short of incredible, effectively shaving off years from the typical development timeline.
However, the two leading vaccine candidates in the United States are constructed in a manner that hints at the potential for expedited development to become a standard practice, particularly if their long-term efficacy aligns with the promising early testing results.
Dr C. Buddy Creech, an expert in vaccines from Vanderbilt University, described the scientists’ response to separate studies confirming the efficacy of the two vaccine candidates as “sheer jubilation.
Creech expressed his perspective at an Infectious Diseases Society of America briefing, stating, “I believe we are stepping into a new era of vaccinology, thanks to the advent of these innovative technologies.
National Institutes of Health
Both vaccines, developed by Pfizer and BioNTech and Moderna in collaboration with the National Institutes of Health, belong to messenger RNA (mRNA) vaccines, representing a groundbreaking technological advancement. In the upcoming month,
U.S. regulatory authorities are poised to make a crucial decision regarding emergency use authorization, which could mark the commencement of a carefully managed distribution plan, initially targeting healthcare professionals and residents of nursing homes.
Substantial investments from corporate and government sources undoubtedly accelerated the rapid progress in vaccine development. Additionally, the unfortunate surge in infections provided scientists with an expedited opportunity to ascertain the effectiveness of the vaccines, significantly reducing the waiting time for crucial data.
Well before the emergence of COVID-19 as a global threat, substantial groundwork had been laid, primarily through two distinct streams of research.
One was conducted at the National Institutes of Health (NIH), while the other was at the University of Pennsylvania. These efforts were greatly informed by prior research on other coronaviruses gained from experiences with past outbreaks such as SARS and MERS.
The traditional vaccine-making process typically involved the cultivation of viruses or virus components, often within significant cell cultures or, in the case of many flu vaccines, within chicken eggs. These materials would then be purified before proceeding to the subsequent stages of COVID-19 vaccine production.
The mRNA method represents a dramatic departure from traditional approaches. It commences with a small genetic code segment containing protein synthesis instructions. The body effectively transforms into a miniature vaccine production facility by selecting the appropriate viral protein to target.
Dr Drew Weissman from the University of Pennsylvania elaborated, “Rather than cultivating a virus in a massive 50,000-liter vessel and then rendering it inactive, we can introduce RNA into our bodies, prompting our own cells to generate the protein that initiates the immune response.
About fifteen years ago, Dr Drew Weissman’s laboratory utilised mRNA to produce various drugs and vaccines. However, early experiments revealed that directly injecting the genetic code into animals resulted in harmful inflammation.
University of Pennsylvania
Through collaborative efforts, Weissman and his colleague at the University of Pennsylvania, Katalin Kariko, who is now associated with BioNTech, devised a slight alteration to a component of laboratory-synthesized RNA. This modification allowed the RNA to elude detection by the inflammation-triggering defence mechanisms.
As Dr Philip Dormitzer, Chief Scientific Officer at Pfizer, explained, “They essentially engineered an RNA that could operate discreetly, like a stealth molecule.
In parallel efforts, additional researchers introduced a lipid nanoparticle coating, essentially a fatty layer, which facilitated the inconspicuous entry of the stealth COVID-19 RNA into cells, thereby initiating the production of the desired protein.
Meanwhile, at the National Institutes of Health (NIH), Dr. Barney Graham’s team pinpointed the ideal target – the spike protein, aptly named for its appearance on the surface of the coronavirus, which effectively primes the immune system.
The importance of precise design must be balanced. It was discovered that the surface proteins that enable various viruses to attach to human cells possess a shape-shifting quality.
They alter their configuration before and after binding to host cells. Using the wrong shape in a vaccine formulation would prove ineffective in preventing infection.
Dr. Anthony Fauci elaborated, “You could introduce the same molecule in one orientation and then in another orientation, and it would yield entirely different responses.”
Vaccine Research Center
This revelation dates back to 2013 when Dr. Graham, the Deputy Director of the NIH’s Vaccine Research Center, and colleague Jason McLellan investigated an unsuccessful vaccine from decades ago designed to combat RSV, a childhood respiratory ailment.
They zeroed in on the correct structure for an RSV protein and acquired knowledge about genetic modifications that could stabilize the protein in its appropriate form for vaccine development. This lesson was then applied to other viruses, including the research on a vaccine for MERS, a close relative of COVID-19, even though it had not progressed significantly before the pandemic erupted.
Dr Barney Graham conveyed, “This knowledge put us in a favourable position to respond rapidly. Once you have that intricate, atomic-level COVID-19 understanding, you can make the protein stable.”
In a parallel development, Germany’s BioNTech had previously partnered with New York-based Pfizer in 2018 to pioneer an mRNA-based flu vaccine. This collaborative effort provided both companies with early insights into how to handle this groundbreaking technology.
As Pfizer’s Dr. Philip Dormitzer stated, “These advancements were in the works; they didn’t emerge suddenly.”
In January, shortly after the novel coronavirus was first reported in China, BioNTech CEO Ugur Sahin redirected their efforts to create a COVID-19 vaccine using the same methodology.
Similarly, Moderna had been utilizing mRNA technology to develop vaccines targeting various pathogens, including the mosquito-borne Zika virus. While this research showed promise, it had yet to progress significantly due to the decline of the Zika outbreak.
Then, on Saturday, January 11, at the National Institutes of Health (NIH),
Dr. Barney Graham woke up to the news that Chinese scientists had shared the genetic blueprint of the new coronavirus. His team promptly initiated work on creating the spike protein in the correct configuration. They shared this critical recipe with Moderna a few days later, setting off a race to develop the COVID-19 vaccine.