Genomic analysis of isolates from the United Kingdom 2012 pertussis outbreak reveals that vaccine antigen genes are unusually fast evolving.

A major outbreak of whooping cough, or pertussis, occurred in 2012 in the United Kingdom (UK), with nearly 10 000 laboratory-confirmed cases and 14 infant deaths attributed to pertussis. A worldwide resurgence of pertussis has been linked to switch to the use of acellular pertussis vaccines and the evolution of Bordetella pertussis away from vaccine-mediated immunity. We have conducted genomic analyses of multiple strains from the UK outbreak. We show that the UK outbreak was polyclonal in nature, caused by multiple distinct but closely related strains. Importantly, we demonstrate that acellular vaccine antigen-encoding genes are evolving at higher rates than other surface protein-encoding genes. This was true even prior to the introduction of pertussis vaccines but has become more pronounced since the introduction of the current acellular vaccines. The fast evolution of vaccine antigen-encoding genes has serious consequences for the ability of current vaccines to continue to control pertussis.

Spreading by snail (Lymnaea stagnalis) defence cells is regulated through integrated PKC, FAK and Src signalling.

Cell adhesion and spreading are vital to immune function. In molluscs, haemocytes (circulating phagocytes) are sentinels and effectors of the internal defence system; however, molecular mechanisms that regulate integrin-mediated spreading by haemocytes have not been characterised in detail. Visualisation of Lymnaea stagnalis haemocytes by scanning electron microscopy revealed membrane ruffling, formation of lamellipodia and extensive filopodia during early stages of cell adhesion and spreading. These events correlated with increased phosphorylation (activation) of protein kinase C (PKC) and focal adhesion kinase (FAK), sustained for 60 min. Treatment of haemocytes with the PKC inhibitors GF109203X or Gö 6976, or the Src/tyrosine kinase inhibitors SrcI or herbimycin A, attenuated haemocyte spread by 64, 46, 32 and 35%, respectively (P

Bordetella pertussis epidemiology and evolution in the light of pertussis resurgence.

Whooping cough, or pertussis, is resurgent in many countries world-wide. This is linked to switching from the use of whole cell vaccines to acellular vaccines in developed countries. Current evidence suggests that this has resulted in the earlier waning of vaccine-induced immunity, an increase in asymptomatic infection with concomitant increases in transmission and increased selection pressure for Bordetellapertussis variants that are better able to evade vaccine-mediated immunity than older isolates. This review discusses recent findings in B. pertussis epidemiology and evolution in the light of pertussis resurgence, and highlights the important role for genomics-based studies in monitoring B. pertussis adaptation.

Adaptive radiation within the vaccine target tetraspanin-23 across nine Schistosoma species from Africa.

High levels of polymorphism in DNA sequences of tetraspanin-23 (TSP-23) were revealed within and between nine different species of Schistosoma from Africa including Schistosoma mansoni, Schistosoma rodhaini, Schistosoma margrebowiei, Schistosoma mattheei, Schistosoma intercalatum, Schistosoma haematobium, Schistosoma guineensis, Schistosoma curassoni and Schistosoma bovis. The greatest levels of diversity coincided with evidence of positive selection (d(N)/d(S)>1) within regions that code for extracellular loops of TSP-23 believed to interact with the host immune system. Kolaskar and Tongaonkar antigenicity predictions of protein sequences were compared across species and high levels of variation in antigenicity were also identified with each species which possessed their own unique antigenic profile. Phylogenetic analysis of TSP-23 proteins suggested evidence of convergent evolution in antigenic lineages as no true inter-species phylogenetic relationships were seen. This could be indicative of host-specific evolution of antigens in different species of schistosomes, a factor that should be considered carefully when developing vaccine targets.