Researchers Warn Production Constraints and Hoarding Could Limit SARS-Cov-2 Vaccine Supplies

Feature MARTIN STORZ/IMAGEBROKER/PICTURE ALLIANCE STORZ/IMAGEBROKER/PICTURE MARTIN Research facilities at CureVac in Tübingen, Germany, one of dozens of firms working on a coronavirus vaccine. CAN THE WORLD MAKE ENOUGH CORONAVIRUS VACCINE? Researchers warn production constraints and hoarding could limit SARS-CoV-2 vaccine supplies. By Roxanne Khamsi

s the world searches for a way to and private funders should give vaccine man- times of high demand. But if billions of people end the coronavirus pandemic, ufacturers money to ramp up their production need a new kind of vaccine for coronavirus, the race is on to find and produce a capacity in advance, even if these facilities are and firms continue making the normal array vaccine. Some optimistic forecasts never used. Although money has been pledged of shots against influenza, measles, mumps suggest that one could be available to help with this, the promises fall short of the and rubella, and other diseases, there could be in 12–18 months — but researchers billions of dollars that public-health experts a production shortage, says David Heymann, are already warning that it might say is needed. an infectious-disease specialist at the London not be physically possible to make Resources for coronavirus will also have to School of Hygiene and Tropical Medicine who Aenough vaccine for everyone, and that rich be balanced against the need for other vac- heads a panel that advises the World Health countries might hoard supplies. cines. Manufacturing facilities around the Organization (WHO) on disease emergencies The production facilities needed will world can churn out hundreds of millions of such as the COVID-19 pandemic. depend on which kind of vaccine turns out to doses of influenza vaccine each year, and com- The WHO says it is also working on a plan to work best. Some researchers say governments panies are used to stepping up production at ensure the equitable distribution of vaccines.

But how that could be enforced in practice isn’t clear. “In a pandemic, the last thing we want is for vaccines to be exclusively accessed by countries that make them and not be univer- sally available,” says Mariana Mazzucato, an economist who heads the University College London Institute for Innovation and Public Purpose. Supply constraints, both physical and political, are a “big worry”, agrees Seth Berk- ley, who heads GAVI, the Vaccine Alliance — a public–private non-profit organization based in Geneva, Switzerland, that aims to increase access to immunizations around the world.

Pick a winner? One big challenge in creating a lot of vaccine quickly is scaling up manufacturing, because the infrastructure needed will differ depend- ing on the vaccine type. The vaccine might consist of a weakened

SANJIT DAS/BLOOMBERG/GETTY SANJIT or inactivated version of the coronavirus, or some part of a surface protein or a sequence Vials of vaccine (not for coronavirus) at a manufacturing plant in Pune, India. of RNA or DNA, injected into the body inside a nanoparticle or another virus, such as mea- vaccines for outbreaks. rules for genetically modified organisms — sles. It might need to be grown in vats of cells, CEPI has also announced funding for six which could make it very hard to fast-track created using a machine that synthesizes RNA other vaccine research teams, including a the process. or DNA, or even grown in tobacco plants. collaboration that wants to re-engineer a If vaccines built from inactivated forms of measles vaccine so that it produces a immu- Cash in advance SARS-CoV-2 prove most effective, it should be nizing SARS-CoV-2 protein in the body. If that An open question is how to ensure that the easier to estimate what it would take to churn works, says Marie-Paule Kieny, a virologist world’s governments and companies invest out doses, because this industrial technology and director of research at INSERM, France’s enough money now, so that vaccines can be has been around since at least the 1950s, says national biomedical research agency in Paris, made quickly in 2021. CEPI says that global Felipe Tapia, who studies bioprocess engineer- it’s possible that measles vaccine-manufactur- funding of at least US$2 billion is needed to ing at the Max Planck Institute for Dynamics ing facilities could be used to make a COVID-19 help develop candidate vaccines and manufac- of Complex Technical Systems in Magdeburg, vaccine, but she cautions that it’s likely that ture them for trials, of which it has been prom- Germany. That said, the production and capacity would have to be increased so as not ised $690 million by national governments. A purification of whole SARS-CoV-2 virus at to disrupt the original focus. further $1 billion is needed to manufacture and high concentrations could require facilities distribute a successful SARS-CoV-2 vaccine for with biosafety level 3 certification. These are This is a challenge that the world, CEPI says. But many more billions of scarce, Tapia says, and could be why very few dollars might need to be plunged into helping companies say they are trying this approach. must be urgently and companies scale up manufacturing capacity, At least a dozen companies are chasing the collectively addressed.” even if that isn’t ultimately used, CEPI chief idea of injecting into the body formulations executive Richard Hatchett told STAT. of RNA or DNA that would provoke our cells Billionaire philanthropist Bill Gates, who into making one of the proteins used by SARS- Other elements in the manufacturing pro- co-chairs the Bill & Melinda Gates Founda- CoV-2. “RNA and DNA platforms may involve a cess might create bottlenecks. ‘Subunit’ vac- tion in Seattle, Washington, also says facilities simpler process — which is likely to make them cines, which are composed of a SARS-CoV-2 should be built in advance. He told US media easier to scale up,” says Charlie Weller, head protein, or a key fragment of one, often need that his foundation would help to pay for this of the vaccines programme at Wellcome, a an adjuvant — molecules added to boost approach, “just so that we don’t waste time” London-based biomedical research funder. the immune response. These might require until we know which vaccine platform will be But no vaccine with this approach has yet been ingredients that could become scarce during the most successful. But the Gates Foundation approved for any disease in humans. a pandemic, such as specific lipids, says Jaap did not provide further details when contacted Moderna, headquartered in Cambridge, Venema, chief science officer of US Pharma- for this story. Massachusetts, which injected its first test copeia (USP), a non-governmental organiza- One firm to secure a large investment is RNA-based coronavirus vaccine into a vol- tion in Rockville, Maryland, that helps to set drug giant Johnson & Johnson, which in March unteer in mid-March, is one firm trialling drug-quality standards. announced a $1-billion partnership with the US this plan: another is CureVac in Tübingen, Another idea to grow vaccines quickly is government’s Biomedical Advanced Research Germany, which says it has the facilities nec- using plants. Cigarette giant British Ameri- and Development Authority to develop a essary to produce up to 400 million doses a can Tobacco (BAT) said in April that it aims to vaccine based on an engineered version of year of its RNA-based vaccine. Both efforts grow vaccines (being developed by its subsid- an adenovirus. This includes a plan to rapidly have received money from the Coalition for iary Kentucky BioProcessing) in fast-growing scale up capacity, with the goal of “providing Epidemic Preparedness Innovations (CEPI), a tobacco plants. But Venema says such plant- global supply of more than one billion doses fund based in Oslo that was launched in 2017 based vaccine products have extra regulatory of a vaccine”. (In an early indication on pricing, as a global alliance to finance and coordinate hurdles to clear, including complying with Paul Stoffels, the company’s chief scientific

Feature MEHDI CHEBIL/POLARIS/EYEVINE A researcher at the Institut Pasteur in Paris works on re-engineering a measles vaccine to trigger an immune response to SARS-Cov-2. officer, has suggested that this vaccine might for Health Security in Baltimore, Maryland. stockpile of vaccines, diagnostics and drugs in theoretically cost around $10 or €10 per dose.) “Most countries have laws enacted that allow the case of an influenza pandemic. But because Governments could help vaccine makers the government to force manufacturers to sell PIP is designed for influenza, it doesn’t apply to plan ahead, says Ohid Yaqub, a health-pol- domestically, and I don’t see this changing,” to the current coronavirus outbreak. icy researcher at the University of Sussex in he says. Countries could agree on a framework sim- Brighton, UK, by signalling how much vaccine CEPI says that there is no agreement yet ilar to PIP for the current pandemic, but it is they plan to purchase and who they would rec- on the principles or rules for a fair allocation highly unlikely that a draft agreement would ommend to be immunized. system incorporated into contracts that can be ready in time for a World Health Assem- A step further would be to set up what are be consistently applied and enforced. There bly slated for May, at which member states known as advanced market commitments to is also no global entity responsible for order- would have to vote for it. And because there purchase drugs at a specific price ahead of the ing the manufacturing of vaccines on a global is so much SARS-CoV-2 already circulating, vaccine being approved, as has happened for scale and paying for it. it’s unclear whether this sort of agreement the distribution for pneumococcal vaccine to “This is a challenge that must be urgently would work, because vaccine manufacturers children through GAVI. and collectively addressed by governments, can access virus samples from private labs, Berkley and others also say that donor coun- global health leaders and regulators while Phelan says. tries could sell bonds to investors as a way to COVID-19 vaccine development is continuing,” It is possible that by the time a vaccine finance vaccines for populations that cannot says Mario Christodoulou, a communications arrives, much of the world will already have afford them. This approach has also been manager at CEPI. been infected with the new coronavirus. Even used successfully before: the International The WHO has tried to step in before to make in that case, however, many might want shots Finance Facility for Immunisation (IFFIm) to sure that vaccine stockpiles are shared equi- to boost immunity. And thinking ahead to raise money for vaccines that GAVI has pro- tably, says Alexandra Phelan, of Georgetown ensure there’s enough manufacturing capac- vided to children. University’s Center for Global Health Science ity for vaccines in any future epidemic is still and Security in Washington DC. After the out- vital, Yaqub says. Laws against hoarding? break of H5N1 in countries such as China, Egypt “The concern for how to manufacture vac- But even if lots of vaccine is made, there seems and Indonesia, WHO member states adopted cines efficiently, reliably and safely is always to be no way to force countries to share it. a resolution known as the Pandemic Influenza going to be there,” he says, “even if we can’t get During the 2009 H1N1 influenza pandemic, Preparedness (PIP) Framework. Under PIP, a coronavirus vaccine or we’ve managed to fig- Australia was among the first to manufacture countries provide virus samples to a network of ure out other ways to deal with coronavirus.” a vaccine, but did not immediately export it labs coordinated by the WHO, with the under- because it wanted vaccines for its citizens first, standing that the organization would consider Roxanne Khamsi is a science journalist based says Amesh Adalja of the Johns Hopkins Center them in an as-needed basis to access a WHO in Montreal, Canada.