Laying Out The Challenges Facing Covid-19 Vaccines
By: Jesse Smith
Tags: Covid 19, Science, Health, Medicine, Coronavirus

Laying Out The Challenges Facing Covid-19 Vaccines

Logistical hangups threaten to hinder the release of the two most anticipated Covid-19 treatments

Earlier this week, news broke that Pfizer’s much anticipated Covid-19 vaccine was found to be 90% effective. This news raised hopes of a vaccine being available by the end of 2020. Around the same time, the FDA granted emergency authorization for Eli Lilly’s monoclonal antibody therapy bamlanivimab. News of these two therapies moving one step closer to availability shed a ray of hope on what is shaping up to be the most challenging phase of the pandemic. Before hopes rise too much, there are a few challenges that need to be addressed before these therapies are widely available.

Getting In Your Cells

Pfizer’s experimental mRNA vaccine is currently leading the effort to protect against Covid-19. mRNA vaccines are a new technology that relies on introducing the genetic code for viral antigens into the human body. This allows the immune system to generate an immune response to the antigens while avoiding the infection itself. Vaccines generally follow this principle in one way or another, but recent technologies have broadened the way that immunity is achieved.

Traditionally, vaccines were developed using dead or inactivated virus particles. The theory being that these particles, although inactivated, would still elicit an immune response. This theory was tested over 200 years ago by Edward Jenner in his development of a smallpox vaccine and paved the way for vaccine development of all kinds.

Pfizer, and their competitor Moderna are developing vaccines that do not contain virus particles, but rather the code for them. In the case of Covid-19, it is the spike protein on the outer surface that elicits an immune response. Pfizer’s vaccine is made up of messenger RNA (mRNA) that codes for the spike protein, assuming that the protein-making machinery in the human body will churn out copies of the spike protein for the immune system to encounter.

This technology comes with a few key challenges. First, mRNA is generally not meant to cross into or out of a cell. In fact, the relative size and electrochemical charge of mRNA molecules preclude them from crossing cell barriers. When a vaccine like Pfizer’s is introduced into the body — through an injection into a muscle in the arm and ultimately through the blood circulation — it is technically still outside of the body’s cells. The machinery to produce proteins from the mRNA — a process called translation — is located inside of the cells.

To overcome this, the vaccine’s mRNA molecules are packaged into fat-like nanoparticles that fuse with the cell’s outer membrane when they come into contact. Once they fuse, they are able to release the mRNA molecules into the cell. Transporting mRNA into the body’s cells was among the first challenges to this technology, but appear to have been solved.

Ice Cold Vaccines

Another major issue facing mRNA vaccines is that mRNA is inherently unstable. mRNA molecules are akin to a Snapchat message, intended to convey a message and soon thereafter be destroyed. In fact, within all of our cells mRNA molecules are being churned out constantly. Many of them go on to be immediately destroyed, often even before they are translated into proteins. This is one of the ways that the body regulates gene expression.

Biological samples stored in a -80 freezer

This inherently fragile nature of mRNA makes it a challenging molecule to use as a vaccine. This is due mainly to its chemical structure. mRNA is single-stranded. Its close cousin DNA is double-stranded and coiled into a helical structure. This structure allows it to resist degradation, which is why DNA analysis is useful in crime scene analysis or archeology. Because of its single-stranded structure, RNA rapidly degrades in the environment.

Because of this, mRNA vaccines need to be stored at sub-freezing temperatures to preserve their viability. To ensure the potency of Pfizer’s vaccine, it needs to be stored at a constant temperature of -70 degrees Celsius. The average kitchen freezer is capable of about -18 degrees Celsius. This poses a major problem, particularly for smaller clinics that aren’t equipped with freezers powerful enough to maintain these temperatures.

Even if clinics were to have freezers capable of those temperatures — which hover around the $20k mark — there is the issue of proper handling of the vaccine prior to administering it. Once a vaccine of this kind leaves the freezer, the clock is rapidly ticking on its life span. Even left out on a counter at room temperature for 30 minutes might be enough to render a vaccine useless.

Update 11/16/20:

Moderna has released data for their mRNA-1273 vaccine showing greater than 95% efficacy. This adds to the growing positive data coming out of clinical trials in recent weeks. Moderna’s vaccine uses similar mRNA technology to Pfizer’s candidate. However, Moderna appears to have eased some of the difficulties around storage of this vaccine.

In a press release, Moderna claims that their vaccine can be safely stored at standard refrigerator temperatures — roughly 2–8 degrees Celsius — for up to 30 days.

Similarly, the mRNA-1273 vaccine can be shipped and stored at -20 degrees Celsius for up to 6 months.

Lastly, Moderna’s mRNA-1273 does not require dilution, a step that is required in Pfizer’s vaccine. This lessens the time required to administer individual doses. Because Pfizer’s vaccine has a 6 hour shelf life post dilution, Moderna’s candidate lowers the likelihood of wasted vaccines

A Little Late To The Party

Monoclonal antibody therapies are a close relative of vaccines. Vaccines stimulate antibody production by training the immune cells — plasma cells — to make antibodies specific to a pathogen like SARS-CoV-2. In many cases, the body retains the memory of the pathogen and will continue to produce antibodies against it throughout a person’s life. Monoclonal antibodies given passively are only effective as long as the antibodies last in the body.

Likewise, antibodies are really most effective early in the disease process. Our bodies have adapted them to recognize pathogens early and trigger a swift immune response. However, once an infection takes hold, the work of antibodies are effectively behind the 8-ball. These two points raise significant limitations to Eli Lilly’s monoclonal antibody therapy bamlanivimab.

Bamlanivimab was granted emergency authorization by the US FDA for the treatment of mild to moderate Covid-19. Participants in clinical trials were excluded based on criteria that indicate severe Covid-19 including low oxygen saturation and reliance on a mechanical ventilator.

So, while bamlanivimab may be effective in lowering symptoms and reducing infection time, it is not proven effective in severe forms of Covid-19.

Another challenge facing bamlanivimab is that it must be administered as an infusion, which would require patients to be present for as long as an hour to receive the therapy. This makes bamlanivimab far more complex than simple injections and raises the question of how a therapy like this could be applied to large numbers of people during a pandemic