Study of Strep A Genomes Brings Vaccine Closer to Reality
Diversity of Group A Streptococcus strains has frustrated vaccine development efforts, but investigators have taken a step closer to finding a common gene signature in nearly all strains.
Investigators have sequenced thousands of genomes and found a common gene signature in nearly all Group A Streptococcus (GAS) strains, bringing a vaccine one step closer to reality.
The study, published in the journal Nature Genetics, was conducted over 10 years in more than 20 countries by the Peter Doherty Institute for Infection and Immunity, the Wellcome Sanger Institute in the UK, and the University of Queensland.
“It is important to know that Strep A is a genetically diverse pathogen and that there are hundreds of Strep A lineages circulating throughout the world that can cause serious infections in humans,” lead author Mark Davies, PhD, Doherty-Sanger Fellow at the Doherty Institute and the Wellcome Sanger Institute, told Contagion®. “In the context of vaccine design, our study identifies that there are a number of proposed Strep A vaccine antigens that are carried by >99% of these genetically diverse Strep A lineages. The use of conserved vaccine antigens is key in the objective of reducing Strep A infections in both high and low-middle income settings.”
Serotype diversity has complicated efforts to develop a vaccine for GAS. The study identified 290 genomic phylogroups after sampling 2083 genomes in what is thought to be the most geographically and clinically diverse database of GAS genome sequences, including 150 emm types, 347 emm subtypes, 39 known M protein clusters, and 484 multilocus sequence types.
“I was surprised about how genetically diverse Strep A is,” Davies said. “Bacterial pathogens like Strep A are dynamic in their evolution and this is important to factor in with vaccine design as there are high numbers of different lineages of strep A circulating in disease endemic settings where a vaccine is desperately needed.”
Currently, primate trials of global conserved vaccine formulations are underway and a human infection model is being developed.
“Our study narrowed down common vaccine antigens in almost all strains of Strep A globally, which is a tremendous step forward in identifying what may work as a global vaccine candidate,” Davies said. “This addresses one of the preexisting vaccine development hurdles, high Strep A serotypic diversity. Furthermore, our database can be used in future vaccine studies to identify globally conserved candidate antigens.
“There is renewed momentum in getting a strep A vaccine into human trials and we now have a strep A vaccine roadmap that has been put in place by the World Health Organization,” he continued. “Substantial financial investment has also been secured from the Australian government into advancing a Strep A vaccine which to date has restricted vaccine development.”
Last fall, the US Food and Drug Administration approved a Strep A 2 molecular assay from Abbott capable of providing results in 6 minutes. The rapid testing is promising for improving treatment of infections, which are known for causing diseases including strep throat, scarlet fever, impetigo, and necrotizing fasciitis.
There has been an uptick in Strep A infections in some countries recently, sparking concern. For example, Japan saw a record number of toxic shock syndrome cases from Strep A in 2017.