Contingency Planning

Lower Dose of Vaccine Administered to Broader Population May Reduce Total Number Infected in a Pandemic

July 12, 2007

A research paper published in the June 2007 issue of PLoS Medicine suggests that infection rates during an influenza pandemic could be reduced significantly if a large number of people were vaccinated with lower doses of pre-pandemic vaccine rather than if a lesser number of people are vaccinated with full doses of the vaccine. The study, conducted by researchers from the University of Hong Kong, used mathematical models to test whether lower optimized doses provide "substantial extra-community level benefits" which outweigh the benefits of vaccinating fewer people with the maximum recommended dose. The authors studied varying doses of three candidate H5N1 vaccines.

The authors conducted two analyses using their mathematical model. The first analysis assumed that people would be protected from infection in an "all-or-nothing" manner, regardless of vaccine dosage. This meant that a certain proportion of those vaccinated would be adequately protected, while others would not have any protective response. The authors found that reducing, or "optimizing," the dose of pre-pandemic vaccine could effectively reduce the attack rate of the disease and protect more people. When the authors modified this model to more realistically account for variation in people’s immune responses to vaccination, optimizing vaccine doses still reduced the influenza attack rate.

In a model scenario that included a high-risk subgroup consisting of children, the authors found that use of the "optimal dose instead of the maximum dose" was even more effective than in other models. This is due to the fact that a higher proportion of infections “originate from individuals in the high-risk group than in the rest of the population." Therefore, by stretching the number of vaccine doses and "preventing a given number of infections in the high-risk group," a larger number of infections would be prevented in the overall population.

As described in an accompanying editorial by Christophe Fraser , an infectious disease epidemiologist from the Imperial College London, the study was based on the premise that vaccines will be only "part of the armory of tools available for pandemic mitigation;" so conducting these mathematical models to determine how best to distribute limited vaccine supplies across populations can be valuable.

Fraser acknowledges the study's limitations, specifically the relationship between vaccine dose and actual immunologic protection has not been studied extensively, especially with regards to pre-pandemic flu vaccines. Nevertheless, Fraser suggests that the study is important because it has the potential to refine policymakers’ goals for a vaccination campaign undertaken with limited stockpiles of vaccine in reserve, i.e., whether to use dose-sparing techniques to minimize overall attack rates or to use larger doses of vaccine to completely protect a smaller number of individuals.

- Center for Biosecurity