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COVID-19 Vaccine Shortages

Shark Liver Oil and Horseshoe Crab blood limit the supply of a COVID-19 Vaccine?

     We’ve already seen the costs of supply chain failures during the COVID-19 pandemic: Delays in the production of simple nasal swabs slowed testing by months even as the pandemic exploded in the US. We saw huge shortages of PPE equipment for front line workers when this epidemic began.  The world is now eagerly awaiting a vaccine, and will need billions of doses as quickly as possible. If the vaccine supply chain fails, the economic and human cost of COVID-19 will be prolonged.

     The multilinked vaccine production chain will take months to set up, which means starting now. Some parts are already seeing investment—glass manufacturers, for example, are ramping up production of vials. But the supply of less obvious inputs needed earlier in the chain is uncertain.

     Vaccine supply chains contain some unusual links, including horseshoe crab blood, shark liver oil and an enzyme that’s one of the world’s most expensive products. Other links rely on novel manufacturing processes that have not yet been implemented at scale. Each link in the chain needs to be stress tested and strengthened. For the potential weak spots, alternative manufacturing processes need to be considered and prepared.

     Vaccine manufacturing requires a long series of biological processes and avoiding contamination is crucial. Endotoxins, which are dangerous molecules shed by bacteria, are one source of contamination. To detect them, each batch of vaccine, along with its vials and stoppers is tested with a substance called Limulus amebocyte lysate. The only known source of LAL is horseshoe crab blood—which means that the supply varies year to year, and we have to be careful not to deplete the crab population. Luckily, a synthetic version of LAL has recently been developed and approved by the U.S. Food and Drug Administration and the European Health Ministry, but companies need time to validate and prepare production to be ready for a COVID-19 vaccine.

     Shark livers are another surprising link in the supply chain for some vaccines. The shark liver oil squalene, which is mostly used in cosmetics and sunscreens, is part of a vaccine adjuvant—a factor that accompanies a vaccine and amplifies its effects by giving an extra stimulus to the immune system. We should be able to repurpose squalene from the cosmetic market to aid in production but it would be even better to have synthetic squalene. This is possible but apparently a lot more expensive at this time. Since the U.S. and Europe control most of the cosmetic market, a Canadian manufactured vaccine may not be possible due to a shortage of shark liver oil.

     Traditional vaccines work by exposing the body’s immune system to a virus that has been weakened or killed; then, when the vaccinated immune system meets the dangerous version of the virus, it’s been trained to attack and kill it.

     Recently, entirely new types of vaccines have been developed that use DNA and mRNA (messenger RNA). These vaccines copy pieces of the virus’s genetic material and then program the body’s own cells to produce the immune-trained antigens. This approach is faster and more standardized than traditional vaccines, and it has potential to be especially safe because it doesn’t involve exposing the subject to the virus.

     DNA and mRNA vaccine technologies have shown promising results and two of the leading vaccine contenders from Pfizer Inc. and Mofderna Inc. use mRNA technology. But mRNA has never been used to produce a commercial vaccine for humans, let alone at worldwide scale. The problem is that mRNA degrades rapidly. To prevent this it must be “capped” by a very rare substance called vaccinia capping enzyme.

     Just over 10 pounds of this VCE is enough to produce 100 million doses of an mRNA vaccine—but the current manufacturing processes for VCE require so much bioreactor capacity that making 10 pounds would cost about $1.4 billion (U.S.). More important, global bioreactor capacity cannot support production at that level while also producing other vaccines and radio-active isotopes to fight cancers.

     Even delivering vaccines can be complicated. Vaccines made with mRNA technology must be stored at very cold temperatures, which may be especially difficult in developing countries. DNA vaccines don’t need cold storage, but they require new methods of delivery such as gene guns that shoot DNA particles.

     Because we don’t know which candidates will work we have to shore up the supply chain for all of these different types of vaccines at once. The world economy is losing approximately $500 billion a month due to COVID-19, so building premature supply chains which cost billions is still a good investment.

     Of course many private companies have already invested billions hoping the vaccine manufacturer they invest in will be the one. Pharmaceutical companies have made the largest investment but many have pledged to keep prices close to cost because they fear public backlash ( or legal action) if they’re perceived as “price-gouging” during an epidemic.

     And if companies don’t stand to profit much from COVID-19 vaccines then they don’t have much incentive to invest in increasing capacity. At that point, in spite of their wealth and financial reserves, they will probably approach governments for handouts to help with production.

     In any case, when you look at all the obstacles in place, a vaccine should not be rushed to market for political gain. Hopefully it will be fully tested and safe and effective before it is introduced to the public.