076 - USING GENOME-WIDE IDENTIFICATION OF TRANSMISSIBILITY TO FIND AND EVALUATE NEW STRAIN-INDEPENDENT PNEUMOCOCCAL VACCINATION TARGETS (ID 302)
Abstract
Background
PCV only targets part of the pneumococcal population, and is vulnerable to replacement by non-vaccine strains. Targeting pneumococcus in a strain-independent manner is needed to maintain the effectiveness of vaccination, but attempts to broadly immunize against core proteins involved in within-host events have not been successful. Prior evidence from genomic data and mouse experiments suggests that transmission rates are variable, and that individual proteins or their allelic variants may cause this variation.
Methods
Using previously published carriage isolates from a population with endemic disease, we modelled population genetic history, and used this to estimate the transmissibility of common strains. Variation in the transmission rate of strains was linked to genetic factors in a genome-wide association study.
Results
We identified variable transmission rates between strains and serotypes. We found that the genes most significantly associated with varying transmissibility included metabolic pathways and immunogenic proteins. We used evolutionary methods to prioritise candidates for a transmission blocking vaccine.
Conclusions
The discovered proteins are promising additions to strain-specific vaccines, and should offer increased indirect protection to the host by blocking between-host events. These candidates will now be tested for their ability to invoke a broad host immune response in an animal model of transmission.
_final/thumbnails/0.jpg)
