The race for COVID-19 vaccines: A deep dive into Moderna’s frontrunner candidate

COVID 19 Microscope
Electronic microscope imaging of the novel Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). (Quapan/Creative Commons)

By Shivani Majmudar
Medill Reports

COVID-19’s sudden emergence as a catastrophic global pandemic, and the absence of medical treatment, left scientists grasping for any means to meet the overwhelming demand for care.

In the historic race to develop a vaccine, Moderna Therapeutic’s candidate, mRNA-1273, stands out as a frontrunner. The biotechnology company went from genetic sequencing to a vaccine ready for human testing in record-breaking time — just 42 days.

Vaccines are developed from the same pathogens (or their structural components) that they are designed to protect against. The infectious strains that are used to neutralize contracting their respective illness – the purpose of a vaccine – are either killed or chemically altered in a laboratory to reduce the severity of symptoms. When injected into humans, the body elicits an immune response exactly as if it were exposed to the disease. The immune system not only fights the infection, but also builds memory to better protect itself if it were to encounter the same pathogen again.

These memory-cells are called antibodies, which are specific to the antigen, or pathogen subunit, that initially stimulated its creation. Antibodies are recognized by its characteristic Y-shape.

Instead of developing vaccines from the intact virus or its protein subunits, Moderna uses the pathogen’s mRNA — the genetic instruction manual for the human body to make proteins. Moderna’s candidate is the first mRNA vaccine to be tested in humans.

Here’s how it works

An mRNA-based vaccine follows the same procedure in the human body as a traditional vaccine. Once injected into a patient, human cell machinery will take up the mRNA and follow its genetic instructions to generate viral proteins. With Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), scientists at Moderna and the National Institutes of Health chose to derive the mRNA sequence for the characteristic spike proteins that decorate the outer surface of the virus.

Moderna Explainer
Mechanism for mRNA vaccine entry and protein synthesis. See full presentation here. (Moderna)

Patients who receive the vaccine then make the same viral particles that we recognize as COVID-19. The body’s immune system identifies these particles as “foreign” and elicits the standard protective and memory response against them.

With mRNA-based vaccines, the human body takes an extra step to make viral proteins, while it would immediately create an immune response if given a traditional vaccine. In this way, the human body is essentially making its own vaccine.

Key advantages and challenges

The biggest asset of using mRNA-based vaccines is their rapid production time. Traditional vaccines can take years to develop — Moderna’s vaccine was created in just six weeks. Part of this speed is because manufacturers do not have to alter the virulence of the pathogen, a generally time-intensive and expensive process, with mRNA-based vaccines. And with COVID-19 surging in the US again, nine months after the country’s first reported case, time is of the essence.

Moreover, quick turnaround times between development to human testing allow researchers more flexibility during rapidly evolving pandemics. Traditional vaccines only protect against the specific strain of the virus that patients are injected with. Therefore in cases where there are multiple strains, as we are seeing with COVID-19, a “one-size-fits-all” solution is ineffective. RNA-based vaccines are a comparatively simple and rapid alternative because they can be easily altered to manage the unpredictable nature of evolving pathogens.

COVID 19 Vaccine Explainer
Of the nearly 150 COVID-19 vaccine candidates, the vast majority follow traditional models of virus or protein-based. Moderna’s candidate is one of the few that fall under the category of nucleic acids. See full tracker here. (Milken Institute Data/Graphic by Shivani Majmudar)

One large hurdle is the highly sensitive nature of mRNA, especially with regard to temperature. The molecule is prone to degradation in environments warmer than 20° C. This poses a challenge to vaccine manufacturers as they try to scale production globally. Although scientists have found some ways to combat this, such as altering the genetic sequence to confer greater stability at higher temperatures or implement freeze-drying procedures, further research is still needed.

The balance between warp speed production and safety

Despite the urgent need, the unprecedented speed at which COVID-19 vaccines have been developed this year has led many to question its safety.

But scientists and experts remind the public that these vaccine models are not new — just the virus that is used to develop it. Even novel mRNA-based vaccines have been tested before for infectious diseases in pre-clinical studies, which demonstrated promising results in animal models.

“It’s important to remember that these vaccines didn’t just suddenly appear,” said Dr. Richard Novak, principal investigator of the University of Illinois-Chicago Phase III clinical trial for Moderna’s vaccine. “We’ve been using technology to develop these platforms for other potentially pandemic infections like HIV and Ebola.”

Novak also stressed the importance of clinical trials, and how Phase I and II specifically are “all about safety and immunogencity.”

See related: Dr Richard Novak: The man behind UIC’s COVID-19 vaccine Phase III clinical trial

Shivani Majmudar covers health, environment and science at Medill. You can follow her on Twitter at @spmajmudarr.