President-elect Joe Biden’s transition team announced on January 8 that he plans to order the immediate distribution of almost all available doses of the COVID-19 vaccines. The plan contrasts the current strategy of the Trump administration, which has been holding back stock to make sure that anyone who is vaccinated will be able to receive the second dose.
The news came amid growing frustration with the speed of the current strategy. At the time of the Biden announcement, the Centers for Disease Control and Prevention (CDC) had distributed 22.1 million doses of the Pfizer and Moderna vaccines, but only about 6.7 million people had received their first shot.
Among the experts who have advocated for switching to giving as many first doses as possible is Christopher Gill, an associate professor of global health at the School of Public Health and an infectious disease specialist with a background in vaccine development.
“Basically, it prioritizes getting the vaccine into more people, rather than ensuring the maximal immune response at an individual level,” Gill says, noting details about the Biden plan are still to come.
The Pfizer and Moderna clinical trials both tested their vaccines as double doses given three to four weeks apart, reporting about 95-percent efficacy following the booster.
“While it is certainly correct that two doses are better than one, when we are in the situation where that leads to half as many people getting vaccinated at all, the result will certainly be that some who were forced to wait will get COVID-19 and some will die,” he says. “It does those poor individuals no good to know that the lucky others who did get the shot will have an even better immune response.”
Gill discussed what is and isn’t known about the Pfizer and Moderna vaccines after a first dose, what it could mean for the spread of COVID-19, and why he considers maximizing first-dose distribution the best option at this time.
What do we know about the efficacy of a first dose of the Pfizer or Moderna vaccine?
Both companies presented data that either directly report, or allow us to infer, the efficacy of a single dose. In both cases it was about 90 percent effective.
Did that protection vary by age? That was not shown. How long would that single dose protect for? That was not shown and cannot be because everyone soon got a second dose. And the period for which this effect is measured is quite narrow—a few weeks at most, because after that the second dose was given and we can no longer assess how a single dose performed any more.
The narrowness of this window is what gives me most unease about the single dose concept, because it leaves many questions unanswered.
You mentioned that the first dose of the Pfizer and Moderna vaccines are about 90 percent effective, but they’ve been generally reported as being 52 and 51 percent effective, respectively. Why?
When you are first exposed to a vaccine—really any vaccine—it takes some time for your immune system to process and react to and develop memory against the antigen(s) in that vaccine. For a first exposure this may take 10 days or more; with a second exposure, assuming that memory has been established, the response is superior and quicker. But effectively that means that COVID-19 cases that occur within the first 10-14 days of vaccination are not telling us yet about the protective value of the vaccine because it is too soon for the vaccine to have had a chance to work yet.
Therefore, a more useful way of evaluating is to look at the frequency of cases that occurred after two weeks, since by then the vaccine has had a chance to trigger the immune response. When you do that for the Moderna and Pfizer vaccines, the protective efficacy after two weeks and before the second dose rises to about 90 percent.
What concerns do you have about this strategy—gaps in evidence, logistical issues, long waits between first and second doses, people never getting a second dose, getting a first dose of one kind and second dose of another, people becoming more lax about precautions…?
We do not live in a perfect world. All of these errors can and will occur. But the most serious error of all is not getting any doses of the vaccine.
What the data show is that two doses of either vaccine are extremely effective (95 percent) at preventing COVID-19, and that one dose is about 90 percent effective—at least in the very short term.
In the real world, some will only get a single dose, and the data we have now tells us that they will derive excellent short term protection. Will they maintain that protection? We don’t know.
What else is known, or can be inferred, about getting a single dose of either of these vaccines?
We know that SARS-CoV-2 infects cells by having its spike protein engage with a receptor on respiratory cells called ACE2, and that all of these vaccines work by creating antibodies that block the spike protein from binding to ACE2. (That is also true of the monoclonal antibodies, such as the cocktail that Trump received when he had COVID-19).
By extension, if you block SARS-CoV-2 from getting into a cell, you prevent it from replicating. If it cannot replicate, it cannot infect the next person in the chain of the pandemic. While it has not been shown in a field study that the vaccine blocks person-to-person spread, we are not blind here and certainly capable of drawing inferences based on what we do know. And based on what we know about the virology of SARS-CoV-2 and how it infects cells via the spike protein, and based on what we have learned about the value of convalescent serum, from the monoclonal antibody studies, and from the data in the FDA briefing documents, it is likely that the vaccine will succeed in also preventing person-to-person spread.
If that is true, then there is value in vaccinating as many individuals as possible during this current period when vaccine supplies are rate limiting. Hopefully, in a few months the supply chain logistics and manufacturing issues will have improved to the point where vaccine supply is no longer rate limiting, and at that point we should obviously work to give the second dose to all that received only one, and prioritize the two-dose series for those getting vaccinated later.
But for now, my opinion is that we are better off vaccinating twice as many people with a slightly inferior immune response, than half as many with 95 percent effectiveness.