Yellow Fever Vaccine Effective Even At Lower Dose

Lowering the dose of the yellow fever vaccine could help extend population coverage even if reduces the vaccine’s efficacy, study says.

AsianScientist (Nov. 29, 2016) – The yellow fever vaccine can offer population-wide protection even when given at a dose five times lower than the standard dose. These findings, published in The Lancet, suggest that fractionating could be an effective strategy to extend the limited supply of vaccines while providing adequate population protection.

Angola has just experienced its worst outbreak of yellow fever in 30 years, with the epidemic spreading to the Democratic Republic of Congo and other countries with low yellow fever vaccine coverage. There is a safe, highly effective vaccine against yellow fever. However, the global emergency stockpile of yellow fever vaccines, which was maintained at approximately 6.8 million doses before 2016, has already run out twice this year.

The World Health Organization (WHO) minimum potency for yellow fever vaccines is 1,000 international units (IU) per dose, but some batches have been found to contain over two million IU per dose, suggesting that fractionated dosing, where the standard dose is divided into fractions, may be feasible.

“We know from previous studies that lowering the vaccine dose by five times provokes a non-inferior immune response, and this provides a strong basis for WHO’s recommendation to deliver fractional dosing in order to extend supply, but we need careful assessment of this strategy and its potential effect on rates of infection,” said Dr. Joseph T Wu an associate professor at the University of Hong Kong.

“This assessment is critical because even if dose fractionation reduces vaccine efficacy, higher vaccine coverage might confer higher herd immunity, in which case the number of infections would be reduced by the indirect effect of large-scale vaccination. The key is identifying how to optimize the limited number of doses.”

Before the WHO campaign, vaccine coverage in Kinshasa was estimated at about 20 percent. If all vaccines had been delivered as standard doses, the authors estimate that coverage would have increased to 37 percent. Without knowing the absolute efficacy of five-fold fractional doses, the researchers modelled different possibilities.

If the efficacy of the five-fold fractional dose vaccine were 100 percent, then 99 percent of the population would be effectively immunized, suggesting that 7.1-7.85 million infections could be averted. At the lowest end of the scale, if the efficacy of the five-fold fractional dose vaccine were only 30 percent, then 44 percent of the population would be effectively immunized, averting 1-1.25 million infections.

“We found that as long as one in five vaccine recipients are fully immunized by the fractionated vaccine, more people would be immunized by vaccinating five times as many people with one-fifth of the dose compared to using the standard dose. In this instance, the benefits of mass vaccination would outweigh the lower efficacy of fractionated dosing for individuals,” explains Professor Marc Lipsitch, Harvard T.H. Chan School of Public Health.

The authors also add that some doses of yellow fever vaccine far exceed the WHO minimum standard of potency of 1,000 IU/dose, meaning that fractionated dosing could be done without dropping below that threshold. They warn that the modelling study used several assumptions, including that there was no seasonal variation in transmissibility, whereas in reality this would be affected by climatic conditions. Therefore they say that achieving high vaccine coverage before the rainy season is particularly important in order to maximize the effect of dose-sparing.


The article can be found at: Wu et al. (2016) Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modelling Study.

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Source: University of Hong Kong; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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