In the Long-Term: A Vaccine
18 months to three+ years
We don’t know when or if SARS-CoV-2 will surge back after this pandemic is under control, or when another pathogenic coronavirus is on the horizon. Our best long-term defense is prevention through vaccination.
The pathway towards vaccine development is long, with many branching paths. The historical approach is to propagate a mammalian cell culture, infect it with the actual SARS-CoV-2 virus under appropriate biosafety containment conditions, then isolate and chemically inactivate the virus. This is followed by purification, formulation and filling to produce the final dose form of the vaccine. Another “live viral” vaccine approach is to genetically modify the virus itself, attenuating and rendering the virus non-pathogenic throughout its lifecycle. Both approaches could trigger the necessary immune response in healthy individuals. Both have their advantages and disadvantages. Both are commonly used in producing today’s vaccines.
Using the actual virus is a faster and more straightforward process, but that speed could levy a high cost. For one thing, a chemically inactivated virus is potentially riskier than one that’s been attenuated. Manufacturing personnel could be susceptible to harmful exposure, and patients are more likely to develop injection site reactions and other adverse effects, including the risk of enhancing the course of the disease rather than protecting against it. A genetically modified virus, on the other hand, is relatively toothless; lab researchers and operators can handle it safely, and it’s more likely to prove safe and efficacious in patient populations. There’s a catch, though: it takes more time to develop the scientific understanding necessary to manipulate a virus so precisely, making certain that it can’t evolve back to the virulent form—and time is hard to come by when trying to respond as quickly as possible to an acute threat like this one. At this point, no one has publicized that they have initiated the development of a live viral vaccine approach for COVID-19.
A third prevalent approach is a subunit vaccine, in which a non-pathogenic fragment of the virus, typically a surface protein without any DNA or RNA, is used to trigger an antigenic immune response and stimulate acquired immunity against the virus. Recombinant microbial or insect cells can be enlisted as host organisms for producing these subunit vaccines. In some cases, the surface protein of the subunit vaccine assembles into virus-like-particles (VLP) with improved recognition by the immune system, but with no nucleic acids and hence no pathogenicity.
New innovative approaches to vaccines are also under development and showing promise. Not long after Chinese scientists published the SARS-CoV-2 sequence, researchers developed an mRNA vaccine candidate and initiated a Phase 1 clinical trial.
Other possible strategies include DNA plasmid vaccines and recombinant vector vaccines.
Opportunity:
- If SARS-CoV-2 persists as a long-term threat, an effective vaccine could accelerate the herd immunity gained from this pandemic and prevent future outbreaks.
Challenge:
- Despite tremendous pressure to accelerate vaccine production, there’s only so much that we can do to collapse the timeline required for necessary safety and efficacy testing. Since most vaccine candidates fail in the clinic, it’s crucial to test multiple strategies.