Scientists led by an Indian origin biochemist are working on a vaccine against a highly infectious bacteria responsible for more than 500,000 deaths a year. Biochemists at the University of California San Diego in the US have uncovered patterns in the outer protein coat of group A Streptococcus that could finally lead to a vaccine against the bacteria that causes toxic shock syndrome and necrotising fasciitis or “flesh-eating disease.”
The researchers uncovered “hidden sequence patterns in the major surface protein and virulence factor” of group A Strep, called the M protein, that limit the body’s immune response against these bacteria.
“At present, there is no vaccine against group A Strep, and our discovery of hidden sequence patterns has offered up a novel way to devise such a vaccine,” said Partho Ghosh, chair of UC San Diego’s Department of Chemistry and Biochemistry, who headed the research.
Ghosh said that one of the biggest obstacles to the development of a vaccine against these bacteria is the “hyper-variability” of the M protein. Group A Strep bacteria have a multitude of different strains, each of which displays a different protein on its surface.
Because our immune systems must recognise these different proteins before launching an immune response with antibodies specific to the outer protein coat, the hyper-variability of the M proteins make it difficult for our immune systems to attach antibodies specific to each these proteins from different strains.
The key to resolving the problem was the recognition that a human protein called C4BP is recruited to the surface of group A Strep by many different protein types.
“This was a puzzle, because the antibody response is specific and limited to a single M protein type, while C4BP binds a broad variety of M protein types, perhaps up to 90 per cent of them,” said Ghosh.
“Group A Strep brings C4BP to its surface to dampen the immune response. We wanted to combat this recruitment by blocking the interaction between M proteins and C4BP, but equally as importantly, we wanted to take advantage of the broad recruitment of C4BP by M proteins that would pave a path to the development of a vaccine,” he said.
“The idea now is to have antibodies do the same thing as C4BP – that is, recognise many different M protein types,” Ghosh said.
“That way, the antibody response will not be limited to one M protein type and one strain of group A Strep, but will extend to most, if not all, M protein types and most, if not all strains, of group A Strep,” he added.
The researchers are now working on developing a vaccine that, they hope, will be protective against most, if not all, strains of group A Strep.
The research was published in the journal Nature Microbiology.