We're hearing, talking, and thinking about vaccine development a lot more than usual these days. What's the actual process for developing a vaccine? And where are we in that process for developing a COVID-19 vaccine? That's the topic of this week's Healthcare Triage.

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We need a COVID-19 vaccine and the sooner we get it, the better! There are plenty in development, but it may very well be at least 12 to 18 months between us and a safe approved product.

And, honestly, it could be worse. There's a whole process to developing a vaccine. On average this typically takes 10 to 15 years and costs about a billion dollars. In the United States vaccine development starts with basic research. This is where scientists set about the task of identifying an antigen, a molecular piece of a pathogen that will induce an immune response, particularly the production of pathogen-specific antibodies. This stage generally takes between two and five years. We did have a head start here thanks to past outbreaks of other coronaviruses like SARS.

For example, we know that these viruses have what's called spike proteins on their surface, responsible for those spike-like shapes you see in all the renderings and for the virus's ability to enter host cells. And we may be able to exploit that in a vaccine.

Once an antigen has been identified, the pre-clinical stage begins. This is where things like cell-culture and animal testing are used to establish an antigen's ability to provoke an acceptable immune response, and to begin assessing its safety. This stage generally takes one to two years and is where many candidate vaccines are scrapped because they fail to produce an immune response. But again, we had a head-start here thanks to previous research into a SARS vaccine.

For the current coronavirus, we've seen at least a couple studies already where monkeys have indeed shown immune-mediated protection from the virus following administration of a vaccine prototype. 

If a vaccine makes it through this pre-clinical stage and is approved by the FDA to move forward, clinical studies with human subjects begin. These consist of three phases with the main goals being determination of safety, appropriate dose, dosing schedule, delivery method, and verification of immune response and disease protection.

Phase I starts with only a small group of subjects (usually less than 100). This is enough to get an idea of safety and tolerability, but not enough to make any big conclusions.

We've seen a little action here as well when it comes to the current coronavirus. On May 18th the biotech firm Moderna reported that their COVID-19 vaccine triggered a sufficient immune response and was tolerated best by humans in two of the three doses used. The full data set is not yet available though.

Those preliminary conclusions are based off data from just 8 subjects, however similar results from a Phase I trial of another vaccine prototype were recently published in The Lancet and were collected from 108 participants.

If Phase I is successful, the vaccine moves on to Phase II, which involves a larger group of several hundred people, making sure when necessary to include individuals with specific characteristics, like relevant health problems, or other factors that increase disease risk. This phase continues to assess the safety of the vaccine and expands the focus on efficacy, making sure the vaccine actually works in humans.

Based on their interim Phase I data, Moderna has announced intentions to move quickly into Phase II, using the two doses they've reported to be most well tolerated. The FDA has approved their 600-participant Phase II study on May 7th.

Phase III will be similar in design to Phase II but is a much larger trial, with thousands to tens of thousands of participants. This expanded testing may reveal rare side effects harder to detect in smaller groups. If a Phase III trial is successful, the FDA completes a regulatory review and approval, after which manufacturing may begin with ongoing quality control measures in place.

Side effects are monitored after the vaccine is released and many vaccines go on to a Phase IV trial for continued evaluation of safety and efficacy.

Given the urgency of the current situation, quite a few shortcuts are being made to this conventional process of vaccine development, allowing us to move at what the National Academy of Sciences has termed "pandemic speed." This includes things like combining phases, moving forward before phases are 100% complete, and getting a head start at the manufacturing facilities we'll need. Even so, lots of people are still unhappy with the prospect of waiting even a year, and some are hoping for a vaccine by this fall.

As it stands any vaccine currently in the works has likely looked promising in animals and is looking hopeful in terms of safety in humans, but we're still only in the first stretch, and there's no guarantee that the ones finishing up Phase I will slide through the rest of the phases.

The French bio-pharmaceutical company Sanofi has teamed up with the drug giant GlaxoSmithKline to accelerate its vaccine development, which has been built upon their work with SARS. But even with that foundation and those resources, they don't expect to have a vaccine until late 2021, and that's if everything is successful along the way.

Keep in mind that less than 10% of drugs that enter clinical trials end up getting FDA approval. It's very likely that we'll run into all sorts of problems, including ultimately ineffective prototypes or intolerable side effects. And if we do come up with an effective vaccine that provides long-term protection, it will take a fair amount of time to produce, distribute, and administer it to a global population.

All things considered, an effective vaccine in one to one and a half years sounds pretty good to me.

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