How many people need to be vaccinated?

Everyone or just some people?

Welcome to Plugging the Gap (my email newsletter about Covid-19 and its economics). In case you don’t know me, I’m an economist and professor at the University of Toronto. I have written lots of books including, most recently, on Covid-19. You can follow me on Twitter (@joshgans) or subscribe to this email newsletter here.

The other day, we talked about the good news associated with Pfizer’s potential mRNA vaccine candidate. A key issue is the allocation of scarce vaccine doses and whether to prioritise protecting the vulnerable or protecting the active. The rationale for the vulnerable is clear: if they are vaccinated, they will be largely protected against the adverse health consequences of Covid-19. For the active, the rationale is less direct: you vaccinate them so that they will not be spreaders of the disease. For a vaccine with 90% efficacy, you may actually protect more of the vulnerable by first vaccinating the active. The other day there was an article in Wired that goes into this in much more detail than I did.

This analysis involved an assumption: vaccination must not only protect people from infection but also suppress their ability to be contagious if infected. These are not the same thing. As Deb MacKenzie (who I can also thank for answering continued emails from me with dense questions) wrote in asking whether a vaccine could get us back to normal:

Moreover, warns Peter Hotez of Baylor College of Medicine in Texas, the first vaccines might stop vaccinated people getting sick, but not prevent them catching and transmitting the virus. “In that case we’ll still require masks and social distancing, until better vaccines come along,” he says.

It all has to do with our immune system. And as I read about that, the more my mind is both blown and not able to work through these issues. As Ed Young recounts:

There’s a joke about immunology, which Jessica Metcalf of Princeton recently told me. An immunologist and a cardiologist are kidnapped. The kidnappers threaten to shoot one of them, but promise to spare whoever has made the greater contribution to humanity. The cardiologist says, “Well, I’ve identified drugs that have saved the lives of millions of people.” Impressed, the kidnappers turn to the immunologist. “What have you done?” they ask. The immunologist says, “The thing is, the immune system is very complicated …” And the cardiologist says, “Just shoot me now.”

It is frigging complicated.

Why is there a difference?

In an earlier post, I noted that this difference existed. It seems important for me to repeat some of that discussion here.

Will taking a vaccine will protect you and protect others from you? For some vaccines, such as that for polio, that is a reasonable assumption. Someone who is immune to the disease is also unable to carry and transmit the disease. For other vaccines, that isn’t the case. That is going to matter for our calculations on who to vaccinate.

Let’s look at why there is a discord between immunity and potential infectiousness. From two infectious disease specialists, Adam Finn and Richard Malley:

Doctors usually explain vaccines to patients and the parents of young children by describing how those protect us from a particular disease: An attenuated form of a pathogen, or just a bit of it, is inoculated into the human body in order to trigger its immune response; having learned to fight off that pathogen once, the body will remember how to fend off the disease should it be exposed to the same pathogen later.

A vaccine’s ability to forestall a disease is also how vaccine developers typically design — and how regulators typically evaluate — Phase 3 clinical trials for vaccine candidates.

Yet the best vaccines also serve another, critical, function: They block a pathogen’s transmission from one person to another. And this result, often called an “indirect” effect of vaccination, is no less important than the direct effect of preventing the disease caused by that pathogen. In fact, during a pandemic, it probably is even more important.

That’s what we should be focusing on right now. And yet we are not.

Thus, we are developing vaccines to protect people from the virus but not from each other. Moreover, even at the trials, they weren’t collecting information (e.g., this interview with Michael Mina where he suggests that they could have been collecting swabs from those in the trial). So we don’t know if vaccinated people might be asymptomatic spreaders.

The HPV vaccine is one example of a vaccine that does both.

The Haemophilus influenzae type B (Hib) conjugate vaccines were designed, and licensed in the early 1990s, to prevent young children from developing serious infections such as meningitis. Soon enough an unexpected and welcome side benefit became clear: The vaccine interrupted the bacterium’s transmission; after its introduction, occurrences of the disease dropped also in groups that had not been vaccinated.

The human papillomavirus (HPV) vaccines were developed to prevent cervical cancer and genital warts in women. They have proved immensely effective among the women to whom they are administered — and up to 50 percent effective at preventing genital warts among unvaccinated men, according to a 2017 study of the health insurance records for 2005-10 of some nine million people in Germany.

Why is there this discord?

To understand why this is the case, remember what it takes for you to become ill from a pathogen, be it a virus or a bacterium.

First, you are exposed to it. Then it infects you. While you are infected, you may infect others. In some cases, the infection develops into a disease. In other cases, it doesn’t: Though infected, you remain asymptomatic.

One way that vaccines can interrupt a pathogen’s transmission cycle is by preventing the pathogen from causing an infection in the first place. This is how many common vaccines — against measlesmumpsrubella and chickenpox — operate.

Other vaccines — like the ones against meningococcal meningitis or pneumonia brought on by the pneumococcus bacterium — can block the transmission of the pathogen by interfering with the infection or by decreasing either the quantity of pathogen that the infected patient sheds or the duration of the shedding period.

Some recipients of the pneumococcal pneumonia vaccine simply don’t get infected with the bacterium; others do get infected and carry the bacterium in their nose, but in smaller amounts and for shorter periods of time than if they had not been vaccinated.

Currently, producing a vaccine with these better properties is not a priority. It is not an FDA requirement and the candidates in trials aren’t really focussing on even measuring it.

But with imperfect vaccines, it will matter.

Conversely, a vaccine that, let’s say, offers older adults only modest protection against developing a disease might nonetheless be very effective, when administered to healthy adults or children, at curbing a pathogen’s transmission in a population overall.

This is the case with the pneumococcal conjugate vaccine. A 2015 study published in the New England Journal of Medicine found that the vaccine reduced the occurrence of pneumonia in inoculated adults age 65 or older by only about 45 percent. Yet, according to a study last year by researchers at the Centers for Disease Control and Prevention and Stanford University, the immunization of infants and toddlers reduced ninefold the incidence of pneumococcal disease in the elderly.

With Covid-19, it may well be that an injected vaccine that stimulates antibodies that protects you does not generate antibodies that also give you mucosal immunity. This means you can still be infected with the virus and it can reproduce and be spread to others even if you are protected yourself. On the other hand, it may be that path is suppressed in some manner by vaccination. The point is that, for any given vaccine, this is a big gap in our knowledge.

How does this impact who and how many to vaccinate?

This gap matters. My discussion the other day was based on a paper that assumes that if a vaccine is 90% effective, it is 90% effective in both protecting individuals and having them be immune in the sense of not spreading the virus to others. This assumption is critical.

Vaccines are often discussed as a means of getting us to herd immunity safely (as opposed to really unsafely without a vaccine/treatment). What does that mean? The virus spreads from infected people to susceptible people. But if you have already had Covid-19, you are no longer susceptible. As the virus makes its way through a population, there reaches a point where there are enough immune people and too few susceptible people for infected people to do as much damage. At that point, reproduction numbers can no longer be above 1 and the prevalence of the virus (the number of infected people) starts to fall. That is the point of herd immunity. We don’t know exactly that point for Covid-19 but the most common assumption is that it is somewhere between 60 and 70 percent of the population.

This leads people to suggest that, if say, 10 percent of the population have had Covid-19 and are already immune, then you only need to vaccinate 50 percent of the population and the vaccine will be enough to cause the pandemic to start to end and not re-emerge. This is one reason why people are not as worried if some fraction of the population refuse the vaccine. So long as they aren’t all in the one place, then if enough people are vaccinated, the pandemic can end.

This all relies on the vaccine conferring immunity in the same way as an actual infection does. But, as I have just stated, that is an assumption. For the moment, imagine the opposite case where a vaccine is 90% effective in protecting people but not at all effective in preventing viral spread. In this case, if you vaccinate 50 percent of the population, the remaining 40% who are still susceptible, will continue to interact with most of the population that can be infected and this time, because half of them are vaccinated, they won’t know it or care about it as much. In this scenario, we end up in a non-socially distanced world of a pandemic with it raging through the unvaccinated part of the population. It will come to an end but at potentially high health costs.

There are several points to note from this notion:

  • There is no such thing (yet) as an immunity passport — a certification that you are safe to go places because you are vaccinated — until we can confirm whether vaccines also stop the spread.

  • The aim has to be to vaccinate as many people as possible for protection purposes rather than stopping at something short because of herd immunity thresholds.

  • The priority should be to vaccinate the vulnerable rather than the active until we know what the vaccine is doing.

  • The current studies have no way of measuring whether the vaccinated are spreaders or not. They aren’t structured for that. Thus, we have to ramp up our monitoring of vaccinated people and measure them for the presence of a potentially contagious virus. In other words, we need to continue to test such people — something I can imagine governments who prioritise now symptomatic people only dropping the ball on. These studies need to be planned and implemented at a wide-scale right now.

  • Specifically, those who are vaccinated, need to be tested en masse to study whether they can still be spreaders. Rapid tests will be more critical than ever. But this time around, getting people to conduct them at home will surely make a huge amount of sense.

What did I miss?