Covid-19 vaccines are here, why do I still have to wait?

Everyone is fed up with the confinement. In recent months, you’ve probably asked yourself this question: “Why is it taking so long to get a Covid vaccine?”

The answer is more complicated than you think. In fact, vaccine candidates are developing much faster than many scientists expected, which means that what you really should be asking yourself is, “How can I get a vaccine so soon?”

According to a recent review in the magazine Nature, there are currently more than 180 vaccine candidates in development. As the review author, immunologist Florian Krammer, predicted: “The data available so far suggests that effective and safe vaccines could be available in months rather than years.”

Many of the reasons you are still waiting are due to the economy – limited resources need to be allocated. But as explained in another review led by pharmaceutical expert Robert Williams, “formulation science plays a critical role in the development, manufacturing, distribution and vaccination phases.”

Development

Formulating pharmaceuticals, creating new drugs, is notoriously expensive and time-consuming. The Covid-19 pandemic has turned formulation into a race.

Traditionally, it will take more than a decade for a potential drug to go from initial design to final production, but it takes less than 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 USA, led by the Advanced Biomedical Research and Development Authority (BARDA), have shortened timescales. Under normal circumstances, pharmaceutical companies risk their own cash to develop a drug and reap the rewards. During the current pandemic, however, government programs are pouring public money into buying products before they exist, basically betting that companies will successfully produce a vaccine.

Another reason for rapid drug development is existing scientific data. The researchers had already studied two closely related (and structurally similar) coronaviruses, SARS-CoV-1 and MERS-CoV, so some vaccine candidates did not need to be designed from scratch and were ready to begin human clinical trials.

Clinical trials for candidate drugs generally involve three phases, evaluating:

1. Safety in fewer than 100 participants, with preliminary data on immunity;
2. Effectiveness in hundreds of people, to determine the optimal dose of the drug;
3. Both efficacy and safety in thousands of participants.

Each phase typically lasts 1-3 years in successive steps, but many Covid-19 vaccine candidates have been tested through overlapping phases in just a few months.

If the results of phase III are favorable, a drug developer can apply for a license to sell their vaccine, which must be approved by a regulatory agency such as the United States Food and Drug Administration (FDA) or the European Agency for Medications (EMA). The approval process usually takes 1 to 2 years, but ’emergency use authorization’ 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.

Manufacturing

In an ideal world in which everyone on the planet gets vaccinated, assuming two doses per person (to prepare and stimulate the immune response), drug manufacturers would need to produce 16 billion doses (twice the world’s population) to satisfy the demand. No single company could not produce that amount of vaccine, so it is encouraging that several pharmaceutical companies have developed potential candidates.

One of the main challenges is expanding manufacturing to meet global demand. There is a big difference between making small batches of a drug for clinical trials and mass-producing them for billions of people.

The companies behind the two promising mRNA vaccines, Pfizer and Moderna, have promised to make tens of millions of doses by 2020; Moderna hopes to ship enough vaccine for 10 million Americans by the end of the year and up to 1 billion doses in 2021. However, the relatively small company has no prior experience bringing any drugs to market, so they are likely optimistic targets.

Another problem is that all vaccines are experimental. Those impressive efficacy figures (95% for mRNA) in phase III trials come from press releases about an interim analysis, so scientists have yet to see the methods and results. Numbers should be treated with caution, as illustrated by the confusing data from the AstraZeneca viral vector vaccine. Even if the statistics stand up to scrutiny, they cast doubt on the claims of other companies and could delay manufacturing.

Drug formulation can also influence large-scale manufacturing. The active agent, such as a viral vector or an mRNA molecule, is not the only important component of vaccines. Often times, a vaccine requires an added substance called an ‘adjuvant’ to elicit an adequate immune response, so a shortage of adjuvants such as aluminum hydroxide (‘alum’) could create a bottleneck for vaccine manufacturing.

Lastly, supplying 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 reserve of just 15 million.

Distribution

If enough vaccine can be made, the next challenge is logistics. Shipping drugs from one nation to another involves transportation along a global supply chain, which will have weak links in the line. Poor countries may not have the necessary infrastructure for mass distribution or administration of the vaccine.

In relation to drug formulation, one challenge is maintaining a “cold chain”. Most conventional vaccines should be kept refrigerated between +5 and +8ºC until they are administered. Transport along the cold chain is especially difficult for mRNA vaccines, which must be kept at freezing temperature: Moderna’s mRNA-1273 needs -20 ° C, while Pfizer’s BNT162b2 requires a freezer at -70 ° C.

Vaccination

The final step is vaccination, which again is largely determined by logistics, although the effectiveness of a vaccine in different groups of people will influence when it can be vaccinated.

Governments have said they will prioritize frontline health workers and the most vulnerable elderly. That could mean that if a drug is available but works in an older group and you are relatively young and healthy, it will take a while before you get the vaccine.

So when will you get the Covid vaccine? it depends on your circumstances. I guess if you live in a wealthy European country of the USA, it definitely won’t be in 2020, probably sometime in 2021 and possibly spring.

Vaccination is in a few months, maybe a year. Until then, to stop the spread of Covid-19 and prevent the death of vulnerable people, we have to continue with short-term interventions: social distancing, hand washing and the use of masks.

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