Delaying second doses could also free up scarce supply

A modeling study suggests a greater population-level benefit for a single-dose Covid-19 vaccination strategy compared to the current 2-dose strategy, even if that single dose is less effective than multiple doses. The study is one of three articles published Jan. 5 in Annals of Internal Medicine that explored different immunization strategies with the goal of vaccinating as many people as possible, as quickly as possible. The analyses make the case that offering single-dose Covid-19 vaccinations or delaying second vaccination may have a greater impact at the population level than current vaccination strategies. The reports were published the same day federal health officials warned that changes to the current 2-dose vaccination strategy “run a significant risk of placing public health at risk.”

The first and second doses of the Pfizer-BioNTech vaccine are approved to be administered within a 21-day window, and the second dose of the Moderna vaccine recommended for 28 days after the first dose. Both vaccines were found to have roughly a 95% efficacy in clinical trials after two doses.

As previously reported by BreakingMED, health officials noted that while it is reasonable to explore changes to the current schedule — such as giving single doses or two half doses of the vaccine or delaying the second vaccination — changes to the current FDA-authorized dosing or schedules are “premature and not rooted solidly in the available evidence.”

“Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from Covid-19,” noted FDA director Stephen M. Hahn, MD, and Peter Marks, MD, PhD, who directs the Center for Biologics Evaluation and Research (CBER).

Quantifying Speed Versus Efficacy of COVID-19 Vaccination

The trio of reports published in Annals included a modeling study designed to quantify the speed-versus-efficacy of Covid-19 vaccination strategies, with the findings highlighting “the steep clinical and epidemiologic costs imposed by a 2-dose vaccination series in the context of ongoing pandemic response,” wrote lead researcher David Paltiel, PhD, of Yale School of Medicine, and colleagues.

Dr. Paltiel and colleagues used a previously published model of COVID-19 vaccine deployment to compare the currently approved vaccine strategies to two hypothetical single-dose alternatives— one achieving lifetime protection and the other achieving stable efficacy of uncertain duration. Both of these single-dose vaccines were assumed to achieve more rapid daily uptake (0.75%) and to take effect 14 days after administration, with assumed efficacies ranging from 0% to 100%.

In the lifetime-protection model, a single-dose vaccine with an efficacy of 55% was found to prevent as many infections as a two-dose vaccine with 95% efficacy. In the uncertain duration of protection model, the efficacy threshold was 75%.

Accelerating Pandemic Control

In a separate analysis, researchers from the University of Washington and Fred Hutchinson Cancer Research Center, Seattle, concluded that, based on a reported single-dose efficacy of 52% (95% CI, 30% to 68%) for the Pfizer-BioNTech mRNA vaccine, “doubling the vaccine coverage with a single dose compared with a 2-dose regimen will accelerate pandemic control” due to the fact that even lack of complete protection at the individual level will lower transmission rates enough to stop epidemic growth.

In addition, Ruanne Barnabas, MBChB, MSc, DPhil, and colleagues argued that providing effective protection for as many people as possible is more ethical and a single-dose vaccine approach could mitigate the higher incidence of vaccine-associated adverse events reported with a second dose.

They further argued that a dosing schedule, which is only partly protective, may reduce behaviors associated with Covid-19 transmission and they suggested that adopting a delayed second-dose strategy in high incidence settings “would contribute data on the effectiveness of single-dose vaccination.”

Alternative Strategies for COVID-19 Vaccine Dose Allocation

Finally, researchers from Stanford University reported on a decision analytic cohort model used to estimate the benefits of alternative strategies for Covid-19 vaccine dose allocation.

Researcher Ashleigh Tuite, PhD, and colleagues compared the current “fixed strategy” approach modeled after current U.S. policy, which reserves half of each allocated vaccine installment for second doses to a hypothetical “flexible strategy” model in which just 10% of available supply for second doses was reserved during the first 3 weeks, with 90% reserved during each of the next 3 weeks and 50% thereafter.

The researchers estimated that assuming a steady vaccine supply of 6 million doses per week, the flexible strategy approach would prevent an additional 23%-29% of Covid-19 cases. “In both scenarios, 24 million people received at least 1 dose by the eighth week, whereas 2.4 million additional people received 2 doses of vaccine in the flexible strategy because millions more received an initial dose during the first 3 weeks; all second doses were administered on schedule (within 3 weeks of first dose) in both strategies,” Tuite and colleagues wrote.

They concluded that current policies which “place a premium on eliminating any possible delays to delivering second doses” by maintaining large reserves of vaccine may unintentionally delay the administration of the first vaccine dose in a large number of people. “We find that under most plausible scenarios, a more balanced approach that withholds fewer doses during early distribution in order to vaccinate more people as soon as possible could substantially increase the benefits of vaccines, while enabling most recipients to receive second doses on schedule,” they wrote.

Growing the Evidence Base for Alternative COVID-19 Vaccination Approaches

In an editorial published with the reports, Thomas J. Bollyky, JD, who is director of the Council on Foreign Relations global health program, wrote that in a public health emergency such as the Covid-19 pandemic, “a powerful argument exists for doing something with less-than-perfect results if it can help more persons quickly.” But Bollyky added that “whether alternative approaches with current vaccines would accomplish this goal is far from clear” given the supply, administration, and demand constraints surrounding Covid-19 vaccine distribution.

“In the United States, Covid-19 vaccine administration will depend on the same overworked and under-resourced U.S. state, local and tribal public health systems that have delivered H1N1 and seasonal flu vaccines,” he wrote. “Despite months of pleas for at least $6 billion to prepare state and local governments for what will be the largest vaccination campaign in U.S. history, Congress only recently appropriated the necessary funds, and it will be weeks more before those federal resources are distributed and put to good use.” Bollyky concluded that while strategies for stretching vaccine supplies “may yet have utility, they will have greater application when and where supply constraints are the rate-limiting steps.”

“A moment may soon arrive when the Covid-19 vaccine supplies are a greater limitation on U.S. vaccinating than at present; therefore, considering various alternative approaches is worthwhile,” Bollyky wrote, adding that, “for now, the priority should be to grow the evidence base by pursuing clinical testing and observational studies to determine whether a single dose or a delayed second dose of the current vaccines will generate immunity similar to that of the FDA-authorized 2-dose regimen.”

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  1. Single-dose Covid-19 vaccination may have a greater benefit at a population level compared to the current 2-dose regimen, even if that single dose is less effective than multiple doses.
  2. Federal health officials warned Monday that changes to the current 2-dose vaccination strategy “run a significant risk of placing public health at risk.”