Everyone’s sick of lockdown. Over the past few months, you’ve probably asked yourself this question: “Why is it taking so long to get a Covid vaccine?”
The answer is more complicated that you might think. In fact, vaccine candidates are being developed much faster than many scientists expected, which means what you should actually be asking is: “How is it that I’ll get a vaccine so soon?”
According to a recent review in the journal Nature, there are currently more than 180 vaccine candidates in development. As the review’s author, immunologist Florian Krammer, predicted: “The data available so far suggest that effective and safe vaccines might become available within months, rather than years.”
Many reasons why you’re still waiting are down to economics: limited resources need to be allocated. But as explained in another review led by pharmaceutical expert Robert Williams, “formulation science plays a critical role throughout the development, manufacturing, distribution, and vaccination phases.”
Formulating pharmaceuticals — creating new drugs — is notoriously expensive and time-consuming. The Covid-19 pandemic has turned formulation into a race.
A potential drug will traditionally take over a decade to go from initial design to final production, but it’s taken under a year to produce potential vaccines against the SARS-CoV-2 coronavirus.
One explanation for the rapid pace of progress is funding. National programs like ‘Operation Warp Speed’ in the US, led by the Biomedical Advanced Research and Development Authority (BARDA), have reduced timescales. Under normal circumstances, pharmaceutical firms risk their own cash to develop a drug and reap any rewards. During the current pandemic, however, government programs are investing public money in buying products before they exist, basically betting that the companies will successfully produce a vaccine.
Another reason for the rapid drug development is the existing scientific data. Researchers had already studied two close relatives (and structurally similar) coronaviruses, SARS-CoV-1 and MERS-CoV, so some vaccine candidates didn’t need to be designed from scratch and were ready to start clinical trials in humans.
Clinical trials for drug candidates usually involve three phases, which test:
- Safety in fewer than 100 participants, with preliminary data on immunity;
- Effectiveness in hundreds of people, to determine the optimum drug dose;
- Both efficacy and safety in thousands of participants.
Each phase normally runs for 1-3 years in successive steps, but many Covid-19 vaccine candidates have been tested through overlapping phases in a few months.
If the results from phase III are favorable, a drug developer can apply for a license to sell its vaccine, which must be approved by a regulatory agency such as the US Food and Drug Administration (FDA) or European Medicines Agency (EMA). The approval process usually takes 1-2 years, but ’emergency use authorisation’ for vaccines means it only takes a month or two. Before the Covid-19 pandemic, no vaccine against any species of coronavirus had ever received a license.
In an ideal world where everybody on the planet gets vaccinated, assuming two doses per person (to prime and boost the immune response), drug manufacturers would need to produce 16 billion doses (double the world’s population) to meet demand. No single company couldn’t produce that amount of vaccine so it’s heartening that multiple pharmaceutical firms have developed potential candidates.
One major challenge is to scale-up manufacturing to meet global demand. There’s a big difference between making small batches of a drug for clinical trials and mass production for billions of people.
The companies behind the two promising mRNA vaccines, Pfizer and Moderna, have promised to manufacture tens of millions of doses in 2020 — Moderna expects to ship enough vaccine for 10 million Americans by the end of the year, and up to 1 billion doses in 2021. The relatively small firm has no previous experience in bringing any drugs to market though, so those are probably optimistic targets.
Another issue is that every vaccine is experimental. Those impressive figures for efficacy (95% for mRNA) in phase III trials come from press releases on an interim analysis, so methods and results haven’t yet been seen by scientists. Numbers should be treated with caution, as illustrated by the confusing data from AstraZeneca‘s viral-vector vaccine. Even if the stats hold-up to scrutiny, it casts doubt on claims by other firms and might delay manufacturing.
Formulating drugs can also influence large-scale manufacturing. The active agent — such as a viral vector or mRNA molecule — isn’t the only important component in vaccines. A vaccine often requires an added substance called an ‘adjuvant’ to prompt an adequate immune response, so a shortage of adjuvants such as aluminium hydroxide (‘alum’) could create a bottleneck for the manufacture of the vaccine.
Lastly, the supply of equipment such as glass vials and injection tools could also create bottlenecks. An estimated 850 million syringes and needles will be needed in the US, which currently has a national stockpile of only 15 million.
If enough vaccine can be manufactured, the next challenge is logistics. Sending drugs from one nation to another involves transport along a global supply chain — which will have weak links along the line. Poor countries might not have the necessary infrastructure for mass distribution or administering the vaccine.
In relation to drug formulation, one challenge is maintaining a ‘cold chain’. Most conventional vaccines must be kept refrigerated at +5 to +8ºC until they’re administered. Transport along the cold chain is especially challenging for mRNA vaccines, which have to be kept under freezing temperature: Moderna‘s mRNA-1273 needs -20°C, while Pfizer’s BNT162b2 vaccine requires a freezer at -70ºC.
The final step is vaccination, which is again largely determined by logistics, although the effectiveness of a vaccine on different groups of people will play a part in when you might get vaccinated.
Governments have said that they will prioritize the most vulnerable, frontline healthcare workers and the elderly. That might means if a drug is available but works in an old age group and you’re relatively young and healthy, it will be a while before you receive the vaccine.
So when will you get a Covid vaccine? It depends on your circumstances. My guess is that, if you live in a rich country in Europe of the US, it definitely won’t be in 2020, probably sometime in 2021 and possibly by Spring.
Vaccination is a few months, maybe a year away. Until then, to slow the spread of Covid-19 and prevent vulnerable people from dying, we have to continue with short-term interventions: social distancing, washing hands and wearing masks.