Thread by @victornizet

Undeniably among our planet’s most prevalent, dangerous, and vexing pathogens—always has been—from 1600s Thomas Sydenham (clear clinical descriptions) to 1800s Theodor Billroth (identified the bacterium/genus) to 1900s Rebecca Lancefield (developed typing scheme)

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Streptococcus pyogenes (Group A Strep) expresses a diverse array of virulence factors allowing it to avoid host immune clearance by antimicrobial peptides, complement, antibodies, and phagocytes—plus potent toxins that damage cells or provoke uncontrolled inflammation

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Why isn’t there a Group A Strep vaccine to prevent the annual global burden of ~700 million cases of strep throat or impetigo, ~200,000 deaths from invasive infections, and ~300,000 deaths from rheumatic heart disease triggered by recurrent Group A Strep infections?

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As opposed to its “cousin” Strep pneumo with its unique bacterial capsules used in today’s many successful conjugate vaccines, Group A Strep’s capsule is composed of hyaluronic acid, mimicking a ubiquitous human tissue component, and therefore entirely non-immunogenic

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The most abundant and immunodominant surface protein of Group A Strep is the M protein which projects as hair-like fimbriae, but there are more than 200 different types of M proteins and antibodies against one may not cross protect against strains expressing another

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There is scant knowledge on the true correlates of protective immunity vs Group A Strep and a paramount concern to avoid vaccine components that could trigger autoimmunity seen in RHD—e.g., conserved regions of M protein, GlcNac side chain of the cell wall carbohydrate

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*BUT* Group A Strep Vaccine efforts have now intensified with leadership of @WHO @NIAIDNews @CARB_X @FondationLeducq #ASAVI a human challenge model #CHIVAS—many top academic labs and vaccine makers such as @GSK @Vaxcyte bringing promising candidates toward human trials

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