Vaccines basically make a person’s immune system think that it’s been exposed to a harmful virus. The trick is to get the body to make antibodies and T cells to fight to fight what it perceives as a threat. Those antibodies and T cells then stand at the ready to fight the real thing in case a person is exposed to the real virus or bacteria.
Once researchers think they’ve found a way to safely trick the body into an immune response you’re ready to start testing it to make sure it works and is safe.
There are a couple dozen candidate vaccines in various stages of testing around the world. Each country has their own way of deciding whether a vaccine is safe and effective.
So, how does the testing system in the US work and how will we know if a vaccine is effective? It really comes down to using the scientific method to develop and test the vaccine using clinical trials and carefully doing a statistical analysis to see whether the vaccine is safe and works (called safety and efficacy).
Phase 0
The first step for most vaccines is to conduct animal studies to see whether a proposed vaccine elicits an immune response, usually in primates. The animals are vaccinated and then researchers check for an immune response. If an immune response happens (antibodies are produced) then they may decide to go to a Phase I human trial.
The SARS CoV-2 vaccine candidates probably skipped this step because it’s optional in emergencies.
Phase I
The first test in humans is a Phase I Trial. During Phase I, small groups of healthy people receive the proposed vaccine (less than 100 people). Some people will get the actual vaccine, and some will get a placebo (e.g. adjuvant or salt water).
The people don’t know whether they’re getting the real thing or not. The vaccine group will usually have a few different doses to measure how that effects the response.
Researchers do periodic blood draws and look to see whether people in each group make antibodies (and usually T cells too). They also look at health outcomes and side effects. They do statistical analyses to estimate how well the vaccine produces an immune response and whether and what kinds of side effects it has. This is done by comparing what happened in each group (vaccine vs. the placebo group).
If Phase I shows that the vaccine elicited a statistically significant immune response and the side effects weren’t bad, then it can proceed to a Phase II trial. It’s not ethical to proceed if the side effects are bad or if it doesn’t work.
There are at least 10 vaccine trials that have completed Phase I.
Phase II
The SARS CoV-2 Phase II trials use the same approach as Phase I- with a vaccine and a placebo group, varying doses, and careful tracking of whether antibodies (and T cells) are made. They also look for side effects in both groups.
The big difference is that Phase II will have more volunteers (usually in the hundreds of people). Just like Phase I, they select healthy volunteers. Phase II will also usually include a wider variety of doses and dose scheduling (timing).
If the Phase II statistics show that the vaccine produced an immune response (at least in some doses and scheduling categories) and if there weren’t bad side effects, they may proceed to Phase III.
This article shows the various trials underway or completed in this category, including the Astrazenica (UK) and Moderna (US) vaccine candidates.
Phase III
Phase III testing is the “real deal” and takes a lot longer than Phase I and II. Phase III trials are done with a much larger number of people (several thousand). The participants are more diverse. Both the challenge and placebo groups have a broader range of ages. They also test a wider variety of doses and administration schedules.
Phase III is the real-world test for the SARS CoV-2 vaccines. Both groups participate in the trial and then go out in the world and live their lives. They continue to come in from time to time for a blood draw to look for the immune response and to check for side effects. In Phase III the researchers also look to see what happens to each group over time.
One thing they look for is how many people in each group gets the disease (in this case COVID-19). This is called examining the “clinical efficacy” (including infection rates and severity).
By comparing results in each group (both by looking at who contracts the disease and the side effects), the researchers can tell whether the vaccine is safe and effective, and if it is, what doses and scheduling are likely to work the best (or if some doses are unsafe).
If Phase III goes well, the company usually asks that the vaccine be approved by the FDA’s Center for Biologics Evaluation and Research.
They listen to the FDA’s Vaccines and Related Biological Products Advisory Committee. That Committee evaluates the safety and efficacy data and the quality of the trials and then makes a recommendation to the FDA Commissioner who ultimately decides whether to approve the vaccine or not.
In the case of the SARS CoV-2 vaccines, the companies will be most likely be asking for Emergency Use Authorization rather than formal approval which would let them begin using the vaccine even though it hasn’t gone through the normal FDA approval process.
Phase IV
This is an ongoing process that all vaccines go through. In Phase IV real world effectiveness is evaluated and there’s a continuing search for uncommon but serious side effects. This monitoring is done by the manufacturer and the CDC FDA vaccine safety system.
Volunteer for a Vaccine Clinical Trial
The COVID-19 Prevention Network and the NIH are responsible for the oversight of the Phase 3 efficacy trials for COVID-19 vaccines in the US. You can volunteer to participate in a Trial by visiting the COVID-19 Prevention Network.
I volunteered for a clinical trial and it only took about 15 minutes. Arizona has been selected for one of the Moderna vaccine test sites because the prevalence of COVID-19 is so high here.