Novel Coronavirus SARS-CoV-2
Credit: National Institute of Allergy and Infectious Diseases, NIH

The COVID-19 vaccine could be the first of its kind

In the race to a COVID-19 vaccine, next-generation platforms might carry us across the finish line. Written by Emily Costa

Per a recent interview with NIAID director Dr. Anthony Fauci, a COVID-19 vaccine may be ready as early as January. If it is, we will have beaten the record set by the mumps vaccine by three years, already a mad dash compared to typical timelines upwards of 15 years. One year to a vaccine is remarkable, and a slew of new vaccine platforms have made it possible.

Research Chemest via Wikimedia Commons
FDA research chemist Judy Regan purifying protein fragments used in developing vaccines in 1987.

Vaccine “platforms”, or the technology applied towards developing and manufacturing vaccines, have broadly expanded in definition over the past 20 years. Traditional viral vaccine platforms, whose vaccines inoculate using uninfectious forms of virus, have provided us long-lasting immunity against diseases like measles, polio, and smallpox. However, these vaccines have their shortcomings, including inconsistent levels of protection from one preparation to the next, sensitivity to heat and light, and potential risks to patients with immunodeficiencies or severe egg allergies. And they usually take many years to develop, creating consequential lags between incidences of outbreak and our ability to halt them. The attenuated measles strain in the MMR vaccine, for example, was only isolated after ten years of growth in laboratory culture.


Novel Coronavirus SARS-CoV-2 Spike Protein
3D printed models of SARS-CoV-2 (back) and its spike protein (front), which helps SARS-CoV-2 enter our cells during infection. Many COVID-19 vaccine candidates deliver the spike protein (or fragments of it) as an antigen. Image Credit: NIH

Advances to genome sequencing and biotechnology have given rise to new classes of vaccines, along with platforms that churn them out at pandemic speed. The COVID-19 candidates represent eight platforms, with relative newcomers producing vaccines that contain SARS-CoV-2 DNA or RNA, each on its own or packaged within a harmless virus. Conceptually, these platforms have many advantages over their predecessors. Their approaches to vaccine design are deliberate and precise, informed by our increasing understanding of SARS-CoV-2’s specific vulnerabilities and the types of antibodies that effectively neutralize it. And their manufacturing processes are rapid, easily scaled up, and compatible with any DNA or RNA sequence, allowing researchers to create multiple variants of the same vaccine and test them simultaneously. Altogether, these innovations can enormously streamline the early stages of vaccine development. In contrast to a decade of watchful culturing, Moderna had readied their candidate, mRNA-1273, three days after the SARS-CoV-2 genome was published.

mRNA vaccines are emerging as strong contenders, with Moderna’s candidate headed for Phase II clinical trials and BioNTech/Pfizer’s candidates in Phase I. They mimic how viruses appropriate our cells’ protein-making machinery, delivering instructions (encoded in mRNA) to make a single viral protein or protein fragment.

Their efficient manufacturing, stability, and safety, as mRNAs are naturally degraded and do not interact with our genomes, have prompted their exploration for personalized cancer therapy and against infectious diseases over the past decade. Though initial clinical testing against rabies and influenza produced underwhelming results, with patients showing modest immune protection and some injection site reactions, there have since been hints of promise, with ongoing trials reporting potent protection at much lower doses. And recent optimizations to the vaccine’s design, such as adding synthetic mRNA bases and packaging the mRNA in lipid nanoparticles, have shown enhanced protein production with fewer unfavorable immune responses in preclinical studies, suggesting room for further clinical improvement.

In many ways, though, time remains a challenge these platforms cannot overcome. After millions of years of coevolution, viruses are exceptional at evading the human immune system. Vaccines train our immune systems to recognize a unique viral molecule, or antigen, and prepare specialized cells and antibodies to deploy against future infection. But viruses are prone to genetic mutations, which can erase previously learned antigens and thereby thwart immune recognition. They’re also capable, through a phenomenon known as “immune enhancement”, of co-opting imperfect immune responses to support their own infection. Such viral countertactics have stymied decades-long vaccine efforts against diseases like AIDS and dengue and make necessary the time to rigorously ensure, first in animal models and then in clinical trials, the safety and effectiveness required of a life-saving vaccine. While next-generation platforms cannot hasten these crucial steps, they might at least allow us to reach them sooner.

For many of the new platforms in the race against COVID-19, victory would also yield their first ever clinically approved vaccine. Time will tell whether they rise to the occasion.

Emily Costa is a science communicator, freelance writer, and scientist researching lung cancer at Memorial Sloan Kettering Cancer Center. She’s also co-host and producer of the Facts Machine Podcast.



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