Take your jab: mRNA vaccine explained

Cassie Guo, Ph.D, Senior Data Scientist, Epidemiology & Abhineet Gupta, Ph.D, Director of Resilience Research

mRNA is a trickster molecule. It is an undercover agent that sneaks into the human body with the mission of sending misleading signals to initiate a war on the immune system. The idea of mRNA vaccine is to synthesize specific mRNA molecules to elicit pathogen-specific immune responses. It is no doubt that the COVID-19 pandemic put such technology into massive adoption. The vaccines are the most anticipated final game to get everything back to normal. But when vaccines against other pathogens (influenza, ebola, zika, etc) were developed, the speed wasn’t even comparable — most vaccines’ development cycles can span over 10 years. We might wonder what it takes to make such vaccines at such rapid speed?

First of all, it is crucial to recognize that the invention of mRNA vaccine is a process which spans over two decades. The figure below illustrates the long journey to effective mRNA vaccine since the discovery of the molecule in the 1960s. Due to the fragility of mRNA that makes it challenging to sustain in human bodies over longer durations, scientists have long tried, and failed to create an effective mRNA vaccine to cure cancer and to protect against infectious diseases. The problem of fragility was not solved until 2012 with the advancement of nanotechnology. Other additional challenges were mostly from the complexity of the immune system. There are about 3000 different clonal types of T cells in one human body. To understand each type of T cell and each pathway requires years of research. At present, even though there have already been mRNA vaccines for pathogens like influenza and zika virus, immunologists are still working to understand the mechanism underlying how pathogen-specific immune responses are elicited.

Compared to other infectious diseases such as influenza and zika, an additional contributing factor for the short development cycle is the enormous amount spent to fuel the research and development of COVID-19 vaccines. The US government spent $13B on COVID-19 vaccine development, with $2.5 billion allocated for general funding and the remainder for advance purchase agreements. This was about 40 times the total budget at the National Institute of Allergy and Infectious Diseases (NIAID) for research and development designated to influenza in 2018. Moreover, the government took a lot of steps to de-risk the vaccine development process for pharmaceutical companies. What would happen if, let’s say, a biotech company spends millions of dollars in researching a vaccine that turns out to be ineffective after 6 months? The government helped to mitigate such financial risks to private companies through advance purchase agreements and investment in infrastructure.

Given these scientific innovations and heavy investment, it is no doubt that COVID-19 vaccines could achieve tremendous success in such a short period of time, as we’ve seen in countries like Israel where a large portion of the population has already been vaccinated. Nonetheless, these efforts and investment in global pandemic preparedness and prevention remain largely insufficient for us to face the next pandemic. In early 2000, the World Health Organization pointed out that the effort for evaluating disease burdens in developing countries is highly needed but scant . This means that if we do not increase our investments in these places, we are courting more upcoming disasters, because the weak links of a pandemic often emerge from developing countries. The consequence of ignoring the effort to prepare for the unknown is the high post-pandemic cost of a pandemic like COVID-19. Long-term investment for prevention, preparedness and forecast can be more effective and less costly than one-time post-pandemic investment, but it is a mentality that is hard to advocate for, since we wouldn’t see the need for mitigation once effective measures make a pandemic become hypothetical. It takes $3.4 billion annual spending to build a robust preparedness system for the global community. This amount is only a quarter of the $13 billion committed for COVID-19 vaccine development, and only 10% of the annualized economic impact if a severe once-in-a-hundred year pandemic occurs. In short, even if only one COVID-19-like pandemic occurs in the next 100 years (which was seen in the last century), we will be getting a 10X annual return on an annual investment of $3.4 billion. If such investments were to be actualized, we wouldn’t need to confront the reality of millions of deaths, thousands of business closures, and enormous costs to the economy.

With decades of research spent on development of mRNA vaccines, and billions of dollars invested in developing vaccines for COVID-19 just in the last year, the suite of approved vaccines provide a cure for our current societal isolation, and is leading us back on a path to normalcy. Yet these vaccines are not the final cure for the chronic negligence of emerging biological threats. We must learn from the past, take lessons from the ongoing challenges, and use scientific principles to meticulously identify the weakest links, so we can invest our efforts and dollars to start building toward our future resiliency now.

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