Q1 2020: A dose of hope for the COVID-19 vaccine — but what next?

The race is on to find a vaccine for COVID-19, with vaccine trials beginning around the world at a seemingly exponential rate. Last week, the UK’s Health Secretary revealed that the University of Oxford would be trialling a coronavirus vaccine in the UK on humans in a matter of days. Pfizer and BioNTech also got the green light for Germany’s first human vaccine trials. And there are five candidates at the clinical vaccination stage and 71 in preclinical evaluation, according to a list compiled by the World Health Organisation.¹https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf Although four companies represent about 85% of the global vaccine development market — GlaxoSmithKline, Sanofi, Merck and Pfizer²https://www.cnbc.com/2020/02/21/coronavirus-brings-light-to-the-35-billion-vaccine-market.html — both legacy players and start-ups have entered the fray.³https://www.marketwatch.com/story/these-nine-companies-are-working-on-coronavirus-treatments-or-vaccines-heres-where-things-stand-2020-03-06 While some projects are focusing on traditional vaccine approaches, others are using newer technology for a coronavirus vaccine in the UK and around the world. 

As explained in a Forum Interview, vaccines can be grouped into three main categories: inactivated, attenuated and genetically engineered. The first two are developed from natural wild viruses, while genetically engineered vaccines are based on genome sequences. There are distinct advantages and disadvantages to each approach — not just in terms of vaccine development but crucially when it comes to making and distributing them. COVID-19 is a global emergency like no other we have faced; once a viable coronavirus vaccine for humans is identified, billions of doses will be needed — and fast. 

The complexity and scalability of vaccine manufacturing a COVID-19 vaccine are huge pressure points, particularly as the infrastructure required will vary across coronavirus vaccine types. This makes it difficult to decide on which areas to invest in, as many facilities won’t ultimately be used. Nonetheless, commentators are emphasising that the vaccine manufacturing piece of the puzzle needs to be addressed sooner rather than later in order to avoid delays. Regulatory hurdles and vaccine manufacturing bottlenecks mean that even once a coronavirus vaccine is ready there could be a 12-month delay before it can be administered. This is, in fact, one of the biggest swing factors that will determine the success of a coronavirus vaccine for humans.

Genetic engineering has a “huge advantage” when it comes to vaccine manufacturing, according to another specialist, as it enables “more or less unlimited quantities” of the virus fragment to be made. With more traditional vaccine approaches, such as inactivated or subunit, “you’re hamstrung by your ability to culture the virus, and viruses are biological projects, highly unpredictable”. Although genetically engineered products are much less tried and tested, he believes they reign supreme from a manufacturing perspective. With mRNA, production can begin as soon as the sequence is identified, which is why the likes of Moderna and CureVac were quick to jump on the case. In addition, while RNA produces an immune response, the particles used are not infectious. 

However, as noted in another Interview, the scale of production required for a fast-moving and global disease like COVID-19 is still exceptionally challenging. Not only do the enzymes used in mRNA need to be highly purified, but knowing precisely which part of the virus structure to target involves a high degree of trial and error. Then, making millions of doses that consistently pass batch release tests presents an additional challenge of its own. Regardless of which approach ends up being successful first, the ability to scale up is paramount.

Moderna, which started human vaccine trials last month, tends to keep its cards close to its chest in terms of its scientific processes (like many other such companies) but is “accumulating trade secrets”. Although it has strong vaccine manufacturing capabilities and has raised significant cash, one expert predicts that the company would have to find a partner for distribution if its coronavirus vaccine was successful. “It really becomes a commercialisation and distribution strategy, so there’s a tremendous amount of interest from larger companies to be able to get involved here,” he said.

In another Interview, a sense of “panic and anxiety” was said to be influencing how COVID-19 vaccines are being tackled. Although such tensions are inevitably going to come into play given the severity of the crisis, the specialist shared his concerns about the lack of long-term safety data associated with newer approaches. For example, despite there being significant momentum behind mRNA, a vaccine made this way has never actually been administered. “Where normally you would conduct a long-term study, extensive studies, to study the safety of these technologies, this is something which is now threatened,” he said. Moreover, further research is needed to learn about the type of immune response that needs to be induced to protect against COVID-19, with genetic predisposition also a significant factor. “Making vaccines that are really protective will require us to have a better fundamental understanding of what I call the immunopathogenesis of the disease,” he said. As noted by another expert, although genetically engineered vaccine development is showing clear signs of promise, “we’ve still got an awful lot more to learn”.

Given how relatively little is known about COVID-19, it seems almost unfathomable that a vaccine could be ready in such a short period of time, with vaccines typically taking up to 10 years to develop. Governments, investors and other institutions are collectively pouring billions of dollars into this global effort, despite the odds being against them. One expert noted that it typically costs GBP 500-600m to develop an infectious vaccine programme using attenuated or live inactive platforms, and probably closer to GBP 1bn for some vaccines. Crucially, it depends on the rarity of the disease and the complexity of manufacturing. The Coalition for Epidemic Preparedness Innovations (CEPI) estimates that it will cost USD 2bn to develop a COVID-19 vaccine within the next 12-18 months, excluding manufacturing. But just as existing research on SARS and MERS — also types of coronavirus — gave scientists a head-start in the quest to find a COVID-19 vaccine, valuable insights will undoubtedly be acquired along the way by all those involved. The vaccine space, which works tirelessly behind the scenes of everyday life, has been brought into sharp focus by this pandemic. With the urgency of the situation requiring scientists to think outside of the box, the vaccine development landscape could see lasting change as a result.