The mRNA Vaccine: A New Era In Vaccinology?

The mRNA Vaccine: A New Era In Vaccinology?


The history of humanity is a history of terraforming and somaforming – of the external and internal transformations and adaptations to a series of increasingly improbable environments and black swan events.


In To Be Taught, If Fortunate (2019), Becky Chambers imagines a crowdfunded effort of interstellar space exploration. In the future, instead of terraforming planets to sustain human life, explorers of the galaxy transform themselves.

Through a revolutionary method known as somaforming, astronauts can survive in hostile environments off Earth using synthetic biological supplementations…. With the fragility of the body no longer a limiting factor, human beings are at last able to explore neighbouring exoplanets long suspected to harbour life.

At the start of every spell of prolonged travel, the crew members apply transdermal drug delivery patches that instigate a cascade of body-wide epigenetic and genetic modulations to allow them to function in the surface conditions particular to wherever they’re headed next: thickened, squamous skin for planets that get more solar radiation than we’re accustomed to on Earth, enhanced muscle mass for planets with greater-than-Earth gravity, and, uniformly, cutaneous photosynthetic capacities to supplement their limited on-board food-growing facilities.


First We Shape Our Tools, Then Our Tools Shape Us

What makes somaforming feel focally technological is that its use entails what ethologists call tooling, a continuing coupling of body and stuff that creates a new interface between the body-with-stuff and some kind of extrinsic object or patient of action.

Vaccines and somaforming are technological, but to the extent that they entail tooling, the tooling either represents an ephemeral rather than an abiding part of their use, or it remains at a remove from the scene of use.

Physiologically, cold-water apnea diving represents one of the most extreme instances of somatic plasticity in the history of humanity. As you would expect, breath-hold divers exhibit enhanced vital capacity (the volume of air they can take in with a breath) and enhanced mobility in the thoracic cage. But these pale in comparison to the thermoregulatory conditioning they exhibit from increased brown adipose deposition.


Crisis Cultivates Creativity

Before 2020, no mRNA technology platform (drug or vaccine) had been authorised for use in humans, so there was a risk of unknown effects. The 2020 COVID-19 pandemic required the faster production capability of mRNA vaccines, which made them attractive to national health organisations, and led to debate about the type of initial authorisation mRNA vaccines should get (including emergency use authorisation or expanded access authorisation) after the eight-week period of post-final human trials.

mRNA vaccines are believed to offer specific advantages over traditional vaccines. Because mRNA vaccines are not constructed from an active pathogen (or even an inactivated pathogen), they are non-infectious. In contrast, traditional vaccines require the production of pathogens, which, if done at high volumes, could increase the risks of localised outbreaks of the virus at the production facility. Another biological advantage of mRNA vaccines is that since the antigens are produced inside the cell, they stimulate cellular immunity, as well as humoral immunity (antigen identification and antibody formation). 

mRNA vaccines also have a production advantage in that they can now be designed relatively swiftly. Moderna designed their mRNA-1273 vaccine for COVID-19 in 2 days. They can also be manufactured faster, more cheaply, and in a more standardised fashion (with fewer error rates in production), which can improve responsiveness to serious outbreaks.

In addition to sharing the advantages of theoretical DNA vaccines over established traditional vaccines, mRNA vaccines also have additional advantages over DNA vaccines. The mRNA is translated in the cytosol, so there is no need for the RNA to enter the cell nucleus, and the risk of being integrated into the host genome is averted.

The COVID-19 mRNA vaccines from Moderna and Pfizer–BioNTech have efficacy rates of 90 to 95 percent. Prior mRNA, drug trials on pathogens other than COVID-19 were not effective and had to be abandoned in the early phases of trials, so the reason for the efficacy of the new mRNA vaccines is not clear.

Physician-scientist Margaret Liu stated that the efficacy of the new COVID-19 mRNA vaccines could be due to the “sheer volume of resources” that went into development, or that the vaccines might be “triggering a nonspecific inflammatory response to the mRNA that could be heightening its specific immune response, given that the modified nucleoside technique reduced inflammation but hasn’t eliminated it completely”, and that “this may also explain the intense reactions such as aches and fevers reported in some recipients of the mRNA SARS-CoV-2 vaccines”. Another view is that they were believed to be a reaction to the lipid drug delivery molecules.


mRNA Money

In late 1987, Robert Malone performed a landmark experiment. He mixed strands of messenger RNA with droplets of fat, to create a kind of molecular stew. Human cells bathed in this genetic gumbo absorbed the mRNA, and began producing proteins from it.

Realising that this discovery might have far-reaching potential in medicine, Malone, a graduate student at the Salk Institute for Biological Studies in La Jolla, California, later jotted down some notes, which he signed and dated. If cells could create proteins from mRNA delivered into them, he wrote on 11 January 1988, it might be possible to “treat RNA as a drug”. Another member of the Salk lab signed the notes, too, for posterity.

Later that year, Malone’s experiments showed that frog embryos absorbed such mRNA. It was the first time anyone had used fatty droplets to ease mRNA’s passage into a living organism. Those experiments were a stepping stone towards some of the most notable and profitable vaccines in history: the mRNA-based COVID-19 vaccines given to hundreds of millions of people around the world. Global sales of which, are expected to top US $50 billion in 2021 alone.

Today’s mRNA jabs have innovations that were invented years after Malone’s time in the lab, including chemically modified RNA and different types of fat bubble to ferry them into cells. Still, Malone, who calls himself ‘the inventor of mRNA vaccines’, thinks his work hasn’t been given enough credit. “I’ve been written out of history,” he told Nature.

In reality, the path to mRNA vaccines drew on the work of hundreds of researchers over more than 30 years. The story illuminates the way that many scientific discoveries become life-changing innovations: with decades of dead ends, rejections, ugly entanglements with politics and profits, but also generosity, curiosity and dogged persistence against the much warranted scepticism and doubt.


Progressive Problems

The nature of progress, is that it presents us with a better set of problems.

Development of prophylactic or therapeutic vaccines against infectious pathogens is the most efficient means we have to contain and prevent epidemics. As there is never a one size fits all approach to health, this does not take away an individuals right to choose (for example those with co-morbid or autoimmune conditions are at higher risk of adverse effects), and fostering trust and transparency in both industry and each-other, respects the limitations of our inherently incomplete frameworks.

Moderna Therapeutics, founded in 2010, has raised almost US$2 billion in capital with a plan to commercialise mRNA-based vaccines and therapies. The fast pace of progress in mRNA vaccines would not have been possible without major recent advances in the areas of innate immune sensing of RNA and in vivo delivery methods.

Extensive basic research into RNA and lipid and polymer biochemistry has made it possible to translate mRNA vaccines into clinical trials and has led to an astonishing level of investment in mRNA vaccine companies. While it is impossible to predict what the next environmental, man-made or space-age catastrophe may hold – the future of mRNA vaccines looks bright.