Nearly a year after the new coronavirus emerged as a worldwide threat, dozens of companies and research institutions started work to create a vaccine for COVID-19. It usually takes years to develop a vaccine, so it was not at all certain that any of the vaccines being developed would actually work.
In fact, when the Food and Drug Administration set requirements for how effective a vaccine needed to be for an emergency use authorization (EUA), it set it at 50% — that’s in the same range as to how effective the flu vaccine is each year.
Less than a year later, there are three COVID-19 vaccines nearing the finish line which are far, far more effective than that. And several others are expected to surpass that mark as well.
Vaccines from two of the manufacturers are expected to arrive this month in Oregon, with others following close behind as the state and country try to end a pandemic they have thus far failed to contain.
Having so many vaccines in the pipeline means harnessing more manufacturing capability, and eventually will allow health officials to tailor vaccines where they’re most effective. Because of the severity of the pandemic, the FDA is expected to approve vaccines for emergency use before the required series of human trials are completed, meaning those kinds of details are currently not as clear as they eventually will be.
“If one of the vaccines is really not suitable for use in people with diabetes, for example, maybe one or two of the others are. It’s important to have options,” said OHSU’s Marcel Curlin, who’s leading a large clinical trial in the Portland area for one of the COVID-19 vaccine frontrunners from AstraZeneca.
What vaccines will be coming to Oregon in December and how do they work?
The first two vaccines expected to get approval from the FDA for emergency use were developed by Pfizer/BioNTech and Moderna. There are many different types of vaccines, but both of these frontrunners utilize a new vaccine technology called “messenger RNA.”
Coronavirus’ genetic code is made of RNA not DNA — think of a double helix missing one of the helixes. To make a messenger RNA vaccine, scientists identify a key piece of that RNA genetic information in the virus — basically, it’s the recipe for a particular protein contained in the germ. Then researchers make artificial copies of that genetic recipe.
When those slices of RNA are injected, they get absorbed into your cells and trick them into following their recipe. The result is that your cells are harnessed to produce the virus protein, which alone doesn’t make you sick. Your immune system then identifies the protein as a foreign invader and learns to fight it off. Later if you become infected with the coronavirus, your immune system already knows how to defend itself.
If they get the regulatory nod, these vaccines will be the first messenger RNA vaccines to gain approval for use, which would be a major scientific milestone — not just in terms of stopping this pandemic, but for vaccine development as a whole going forward.
Are the vaccines effective?
Early in the process, there were questions about how effective messenger RNA vaccines would be — and the findings from the early trials have far exceeded expectations.
“They’re both phenomenally effective (at preventing symptomatic disease),” Oregon Health Authority Senior Health Advisor Joe Sullivan told health care workers across the state.
The Pfizer vaccine is showing 95% efficacy, which was confirmed this week by the FDA. Moderna says its vaccine has a 94.5% efficacy rate. This means people who receive the two doses of vaccines required for the vaccine to be most effective are around 95% less likely to experience symptoms of COVID-19 than those who aren’t vaccinated. And for those who end up defying those odds and getting COVID-19 despite the vaccine, they did not get seriously ill.
OHSU professor Mark Slifka says for vaccines, 90% efficacy is usually considered the “golden ceiling.”
“No vaccine could give you 100% protection, but you want it to be high,” he said, adding that the efficacy rates were calculated soon after the second vaccine dose was administered.
“The immune response may go down over time. But if you were starting off, for instance, at only 50% protection at the peak, well then that’s pretty bad because it could fall off from there,” Slifka said.
It’s still unknown how long the vaccines will protect people from COVID-19, but we do know that getting both doses is important.
“You need that second dose. You need that boost in order to mount the immune response that the vaccine can provide. That second dose really does make a difference,” said Peggy Hamburg, former commissioner of the U.S. Food and Drug Administration, in a briefing.
What other vaccines are in the pipeline?
At least two other COVID-19 vaccines are expected to seek FDA emergency use authorization over the next few months — one is from AstraZeneca and one from Johnson & Johnson.
Both of these vaccines are “viral vector” vaccines.
The AstraZeneca vaccine starts with an unrelated cold virus that affects chimpanzees but not humans. Researchers disable the virus so it can’t replicate, and then they insert genetic material from coronavirus into it.
“It’s a safe vehicle… to introduce (coronavirus) protein and let the immune system get a look at it without actually being exposed to COVID. And therefore, the person who’s vaccinated, their immune response is in place already when the person gets exposed to COVID,” said OHSU’s Curlin.
Johnson & Johnson’s vaccine uses a similar technique, with a different version of the cold virus used by AstraZeneca. The company had previously created a vaccine for Ebola and an experimental vaccine for HIV using the same disabled cold virus. This time around scientists just inserted genetic material from the coronavirus.
Both the AstraZeneca and Johnson & Johnson vaccines lost some time in the testing process when the FDA halted the human trials because a test subject became ill. But in both cases, after an evaluation of the data, regulators decided that the illnesses could not be connected to the vaccine and authorized the clinical trials to resume.
Are there any winners emerging in the vaccine race?
Getting to EUA first or close behind definitely makes a vaccine a winner on one front — namely that there’s essentially an unlimited demand and you’re only really competing against your own ability to make and distribute your product. All vaccines approved over the next few months will benefit from this global demand.
The AstraZeneca and Johnson & Johnson vaccines are priced at around $4 and $10 per dose respectively. AstraZeneca has said it will not seek to profit off the COVID-19 vaccine during the pandemic. Pfizer and Moderna’s price tags range from $19-$37 per dose. Currently, all of these costs are being picked up by the federal government, but notably, the U.S. has ordered three times as many AstraZeneca vaccine doses as it has each of the other three.
Johnson & Johnson is also testing a one-dose version of its vaccine, which could give it a distinct advantage if approved.
Vaccine storage has also emerged as an issue, with health departments — including the Oregon Health Authority — struggling to secure the ultra-cold (-94 degrees F) storage needed to preserve the Pfizer vaccine. Moderna’s version requires more-standard freezer capabilities. But both Johnson & Johnson’s and AstraZeneca’s vaccines can be stored in refrigerators for several months.
Are the vaccines safe?
This is one of the main questions that the FDA is considering as it evaluates clinical trial data from the vaccine makers. It will use this data to determine whether to issue emergency use authorization for the vaccines.
In addition, Oregon is part of a four-Western-state vaccine safety working group that is independently reviewing the same data. That group will issue a separate opinion on whether the vaccines are safe enough to use.
The three phases of clinical trials required by the FDA for vaccine approval are set up to answer safety questions. The early trials are designed to identify immediate and shorter-term side effects — things like headaches, fatigue, fever, soreness at the injection site, and occasionally more serious reactions. If the side effects are too serious, then the vaccine cannot advance to the next phase of clinical trials.
In order to apply for EUA, the vaccines must have some intermediate results back from the Phase 3 trials, which can normally last several years. The early approval means data about any long-term effects of the vaccines are not yet complete — which is not ideal.
But also not ideal: thousands of people are dying of COVID-19 every day in the country; there’s resistance to safe, non-invasive and widely-available COVID-19 prevention measures like masks; and shutdowns are causing real economic harm to large swaths of the U.S. population.
“Do the benefits outweigh the risks when it’s a serious, life-threatening disease or condition when there aren’t other alternatives? That’s the decision that FDA will be making,” says former FDA Commissioner Hamburg.
How many people need to be vaccinated to reverse the course of the pandemic?
This is a question that does not have an exact answer. But one thing holds true.
“The more people get vaccinated, the quicker we get back to normal,” OHSU’s Slifka said.
Using a very simplified calculation, Slifka says if every infected person is assumed to spread coronavirus to two others, then the case numbers will start to drop as we cross the 50% vaccination rate. This does not take into account changes in prevention measures or immunity derived from a previous infection. Oregon’s actual person-to-person infection rate is thought to be closer to one COVID-positive person infecting an average of 1.25 others.
Achieving herd immunity will likely require another jump in vaccination rates. Herd immunity occurs when a large enough percentage of a community becomes immune to a disease — either through vaccination or prior infection — making it unlikely the disease will be able to spread between people.
The amount of immunity required to achieve this depends on the disease. Measles, which is highly contagious, requires nearly 95% of a population to be immune to achieve community-wide protection. Coronavirus isn’t as contagious, so the vaccine requirements are lower.
On Tuesday, National Institute for Allergy and Infectious Disease Director Dr. Anthony Fauci said in order to achieve herd immunity nationwide, 75% of the population will need to be vaccinated for COVID-19.