Stretching COVID-19 vaccine supply with single doses

Despite the development, validation, and rollout of COVID-19 vaccines, SARS-CoV-2 continues to spread worldwide and cause disease and death among individuals who are yet to receive the vaccine. Although multiple highly effective vaccines are now available, for optimal protection, most require two doses given three weeks apart. Given the global vaccine shortages that will continue to delay vaccination, stretching vaccine supply by limiting doses to one per person is attractive as a potential strategy, as the benefits of fractional dosing a larger population may compensate for the loss in protection in an individual. However, the success of a single-dose campaign hinges on the effectiveness of the first dose and the prioritization of vaccine recipients.

A recent paper published in Nature Communications by Dr. Laura Matrajt and colleagues from the Vaccine and Infectious Disease Division asked if one dose of vaccine would be sufficient to decrease negative COVID-19 outcomes. “When we started this work in September 2020, we didn’t even know how efficacious vaccines will be, but we did know that most of the vaccines would require two doses. We aimed to determine under which conditions giving twice as many people a single dose of vaccine might be the optimal use of very scarce vaccine supply,” said Dr. Matrajt. Building on their previous model of SARS-CoV-2 transmission, the authors created a deterministic age-structured mathematical model based on the population of Washington state. This model considers what percent of the population has pre-existing immunity from infection, the prevalence of SARS-CoV-2 infection, and the percent of the population still susceptible to infection. The model simulated six months following vaccine rollout in early 2021.

The model assumed a baseline transmission rate, defined by the effective reproductive number, or the number of susceptible people who will become secondarily infected from one infected individual given pre-existing immunity and social distancing measures. The model was then used to predict optimized vaccine strategies based on three possible single-dose efficacies and either low or high background transmission rates. The authors considered that a vaccine with less than 100% efficacy could affect a vaccinated person in three ways: decrease likelihood of infection, decrease risk of symptomatic infection, and decrease the risk of transmission to susceptible people. These three outcomes could then influence cumulative infections, cumulative symptomatic infections, cumulative deaths, number of non-ICU hospitalizations, and number of ICU-hospitalizations, all outcomes of public health interest.

The authors went on to simulate various vaccine campaigns based on different combinations of background transmission and single-dose efficacy to define the optimal vaccine strategy needed to decrease a given outcome. “Using mathematical models paired with optimization algorithms we determined that there is not a ‘one size fits all’ way to allocate vaccine. Instead, the best use of vaccine depends on how efficacious a single dose of vaccine is, what is the level of ongoing transmission when vaccination starts, and what the goal is, to minimize deaths or transmission,” explained Dr. Matrajt. She went on to describe optimal vaccine strategies in differing scenarios, including which populations should be prioritized: “If the vaccine is highly efficacious after one dose, then vaccination campaigns with a single dose are optimal. With high ongoing viral transmission, it is optimal to allocate this vaccine to the older, most at-risk population. With low ongoing viral transmission, age prioritization is not as important. However, if one dose of vaccine has low or moderate efficacy, then it is better to give two doses and to allocate them to the high-risk population.”

These findings suggest that in certain scenarios, vaccinating a larger number of people with a less-effective vaccine results in better public health outcomes than does giving fewer people a more protective double-dose. However, factors such as efficacy of a single dose and background transmission rates must be carefully considered before opting for single-dose vaccine campaigns. Additionally, higher-risk populations, such as the elderly, must be prioritized for vaccine eligibility. This work “emphasizes the need to determine how efficacious a single dose of vaccine is, and how durable this response is,” explained Dr. Matrajt. Going forward, they “are planning on developing similar methods to determine optimal distribution of vaccine when several vaccines and variants are present,” Dr. Matrajt said.

UW/Fred Hutch Cancer Consortium members Holly Janes and Josh Schiffer contributed to this work.

Matrajt L, Eaton J, Leung T, Dimitrov D, Schiffer JT, Swan DA, Janes H. Optimizing vaccine allocation for COVID-19 vaccines shows the potential role of single-dose vaccination. Nat Commun. 2021 Jun 8;12(1):3449. doi: 10.1038/s41467-021-23761-1.

This work was supported by the Fred Hutchinson Cancer Research Center, the National Institutes of Health, and the Centers for Disease Control and Prevention.