There has been much discussion about vaccine expectations because of the SARS-CoV-2 pandemic. Many people think that a good vaccine will completely eliminate the disease. That is the lofty goal of vaccination. We eradicated polio because of vaccines. We would love it if all vaccines eliminated the disease entirely, but that’s not the reality for many vaccine-preventable diseases. Take the flu vaccine as an example. It doesn’t always stop infection from the flu. A lot of people use that to claim it’s not a “good” vaccine. That claim is a misunderstanding of what the goals of vaccination are. Eliminating infection, called “sterilizing immunity,” is not the goal of every vaccine.
Most vaccines don’t actually provide sterilizing immunity. Vaccines for diseases that have a long incubation period sometimes do, because the immune system has time to act on the pathogen before it’s infectious, but vaccines for pertussis, rotavirus, conjugate pneumococcal, influenza, etc. do not. They do usually reduce transmission.
So, let’s look at what makes a good vaccine and the goals of vaccination.
Long Lasting Protection
For some pathogens, like the flu, long-term immunity is seemingly impossible to achieve. The flu, which is actually four types of Orthomyxoviridae, changes quite a bit from year to year. We can’t yet design a vaccine to account for the changes. For some other pathogens, immunity wanes over time. Tetanus, diphtheria, pertussis is recommended every 10 years because of waning immunity. The perfect vaccine would offer lifetime protection, but good vaccines are scheduled and designed to boost immunity when needed. That’s why we get boosters and have vaccine schedules.
We aren’t sure what kind of immunity a SARS-CoV-2 vaccine will provide yet, but natural immunity to the virus appears to wane. There have been a few case reports of reinfection. With any pathogen, we expect that immune response within the population will vary. Some people will have a strong immune response. Some will have a weak one. Most will have a response that’s somewhere in the middle. The reinfections could just be those outliers who didn’t mount a good immune response. The majority of us could have a better, longer-lasting, response in the middle. We don’t know.
Even if the majority of us don’t mount a long-lasting natural response, it doesn’t mean that a vaccine won’t offer better immunity than natural infection. They often do. Only time will tell. We may have to have a yearly shot like the flu, or maybe a booster every few years like some other vaccines. It doesn’t mean, as headlines claim, that a vaccine against coronavirus won’t work. It just means we have to design one that works with our immune response.
Protection from Severity of Disease
A criticism I hear about the flu vaccine quite a bit is that “it isn’t very effective.” They usually aren’t talking about the long-term effectiveness I discussed above. They’re talking about the 40-60% of people who get the flu vaccine and still get the flu. Remember: sterilizing immunity isn’t always the goal. The secondary goal of the influenza vaccine is to reduce the incidence of severe disease. Our current flu vaccines are very good at that.
It’s been shown that influenza immunization significantly reduces the risk of bacterial complications associated with influenza and shortens the average hospital stay of those infected by the flu. The majority of people who die “from influenza” don’t actually die from influenza. They die from secondary infections caused by influenza, and sometimes end up with organ damage from the treatment of those infections. It’s theorized that while your immune system is busy fighting influenza, other opportunistic bugs like S. pneumoniae and Pseudomonas move in. If we can eliminate some of those infections, we’ve eliminated a big part of influenza mortality.
Aside from bacterial infections and hospital stay, infection with the flu can cause heart attacks and myocarditis. There’s a significant body of evidence that finds the influenza vaccine prevents up to 45% of heart attacks, which is about the same risk reduction as smoking cessation.
That’s pretty impressive for a vaccine that’s not “good.”
There’s a concern with just preventing serious illness that we should consider in the context of SARS-CoV-2. People who get the flu shot and get infected may be protected, as explained, but their friends and families aren’t. That’s why some experts believe that even with a SARS-CoV-2 vaccine, we may still need to have some restrictions in crowd size and possibly still need to wear masks until the majority of the population is vaccinated. Why?
As a health care worker, I may have the opportunity to get the vaccine early to protect myself. I may decide to drop all my precautions and walk around like it was 2019. I’m vaccinated and safe. However, I may get infected and never know it. Hopefully, I’d be protected from disease and symptoms myself, but I could be interacting with unvaccinated patients or coworkers and spreading coronavirus around. We don’t know enough to know if that’s going to happen, but it’s one possibility. The initial run of vaccines probably won’t be enough to vaccinate everyone who is at high risk. We may need still need to protect them, even if we’re protected ourselves. That still doesn’t make it a bad vaccine. It’s just probably not going to be the perfect vaccine. Welcome to medicine, where nothing is perfect.
Many of our vaccines are unlike the flu vaccine and do provide a immunity that basically prevents infections, or sterlizing immunity.
Few Side Effects
Another thing we want in a good vaccine is for it to have very few side effects. A vaccine that harms more people than the disease isn’t very smart. That’s why a few of the SARS-CoV-2 vaccine candidate trails have been stalled. They want to make sure that these vaccines aren’t causing more harm than good.
Our current vaccines don’t have a large incidence of severe adverse effects. Guillain-Barré is among the most serious, and it’s really similar to the cytokine storm syndrome we’ve been hearing about. It’s basically an overreaction of your immune system.
More common side effects are things like a mild fever or feeling a little sick. For me, my arm always hurts for a few days and I usually feel nauseous after the flu shot. I don’t consider that a big deal. That vague sick feeling is usually just your immune system turning on. It’s really not concerning, especially with a “killed” virus. I’ll write more about vaccine types in part 2.
If you have trouble breathing, wheezing, swelling or hives, that is not normal. Vaccines can rarely cause serious allergic reactions or other problems. We want to avoid vaccination in those severe cases. Luckily, some of our vaccines provide a mostly sterilizing type of immunity, so if Joey Jr. can’t get the pertussis shot but everyone else in his class does, Joey would be protected too. (Note: The pertussis vaccine isn’t sterilizing, meaning it doesn’t completely stop transmission. However, like most vaccines, it reduces transmission. The SARS-CoV-2 vaccine may too).
Easy to Administer and Store
Another thing we really want vaccines to be is easy to store, ship, and administer. That’s a supply chain issue, but it’s important for access.
Some of the SARS-CoV-2 vaccine candidates require unusual cold storage which means only limited clinics and pharmacies will be able to have them. Those clinics and pharmacies probably won’t be in underserved areas. We would prefer a vaccine that either needs normal refrigeration or none at all.
We want vaccines that are easy to administer and have a low barrier to effectiveness. Vaccines like the PPSV23 (for pneumonia) are pretty easy. You usually just need one shot and you’re done. That’s a pretty low barrier to effectiveness. We try to make sure everyone over 65 who is admitted into the hospital for anything gets their shot. They’re usually vaccinated for life after that. Vaccines like the influenza vaccine are more difficult because you have to get them yearly. Many vaccines, like the new shingles vaccine and the hepatitis vaccines, are a series where you have to get a shot and a booster or two for the best immune response. That can be tricky, especially in underserved areas and people with poor transportation and access. It’s common to forget or not have access to the booster.
Most of the SAR-CoV-2 candidates are going to require a booster. I think there’s currently one in phase 2 that is one shot, but chances are one of the boosted ones will be first to market.
For a new vaccine, there’s also a supply and demand issue for clinics and pharmacies. We’ve seen this with the shingles vaccine as well. Do you vaccinate everyone with the first in the series and hope for more stock in a few months (or whatever the time period will be) or do you set stock aside for the repeat dose? Most won’t set stock aside. What happens if you don’t have stock later? How far schedules can be pushed and still ensure a good immune response varies with the vaccine, and I doubt we’ll have that information for SARS-CoV-2 anytime soon.
In part 2, I’ll discuss the different types of vaccines and why would chose, say a vaccine made in chicken eggs over cell-cultured vaccine or a recombinant vectored vaccine.