Common surface protein sequence in group A strep could lead to vaccine

UC San Diego biochemists have identified patterns in the surface protein of group A Streptococcus. The findings could result in a vaccine for the bacteria, commonly associated with mild illnesses such as strep throat, but which can cause life-threatening disease, including toxic shock syndrome and necrotizing fasciitis, or “flesh-eating disease.”

There is currently no licensed vaccine for group A Streptococcus. Invasive group A strep causes as many as 1,800 deaths each year in the U.S., according to CDC estimates. Developing a vaccine against the bacteria has been challenging, because it has many different strains that all display different surface proteins. The immune system launches a response to each specific protein, so recognizing one surface protein will only result in immunity against that particular strain.

The UC San Diego team discovered “hidden sequence patterns” in the bacteria’s major surface protein, dubbed the M protein, that inhibit the body’s immune response to group A strep.

“We remain vulnerable to infection by other group A strep strains that display other types of M proteins on their surfaces,” said Partho Ghosh, chair of UC San Diego's Department of Chemistry and Biochemistry, in a statement. “This is because the antibody response against the M protein is almost always specific to the sequence of that M protein, and M proteins of different types appear to be unrelated in sequence to one another."

They found that the M protein “recruits” a human protein, C4BP, to the bacteria’s surface in order to weaken the immune response. While the immune system responds individually to each M protein type, the C4BP protein binds to as many as 90% of M proteins, Ghosh said. This near-universal binding revealed that the seemingly unrelated M proteins have a common sequence pattern on their surface that could serve as a target for a vaccine.

The team is now working on a vaccine against group A strep. The hope is to get antibodies to behave the same way as C4BP and recognize many different M protein types via the common sequence pattern. "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," Ghosh said.