TABLE 1.
Desirable strain characteristic(s) | Rationale | M75 611024 details |
---|---|---|
Definite but uncommon contemporary cause of symptomatic pharyngitis | Pharyngitis is the critical early target for GAS vaccine development; historical CHIM studies offer a template for a reliable and safe protocol; GAS pharyngitis is most common in childhood and adolescence, suggesting previous exposure and immune memory could prevent experimentally induced disease in adult volunteers | From a child with symptomatic GAS pharyngitis in Melbourne, 2011; preexisting immunity in adults is unknown (no correlate of protection); ≤5% of strains in most recent pharyngitis studies are emm75 |
Should cause skin infection | Common GAS skin infections (e.g., impetigo) will also be important in initial vaccine field trials; ideally, the pharyngitis CHIM strain(s) should also be suitable for use in a potential future human model of cutaneous GAS infection | E pattern generalist (throat and skin infections); cluster E6 is linked phylogenetically to D pattern skin isolates |
Uncommon cause of invasive GAS disease and immunological sequelae | GAS pharyngitis can lead to locally invasive infectious complications (e.g., retropharyngeal abscess), severe invasive infection (e.g., streptococcal toxic shock syndrome), acute rheumatic fever, and glomerulonephritis | ≤5% of isolates in recent reports of invasive GAS are emm75; from 2000 to 2016, 403/17,002 (2.4%) typeable invasive isolates reported to the U.S. CDC’s Active Bacterial Core surveillance were emm75 (Chris A. Van Beneden, personal communication, 11 September 2018) (41, 42); emm75 strains rarely associated with ARF/RHD or APSGN (1) |
Should have predictable and limited virulence and be suitable for use in animal models | Whole-genome sequencing, in vitro assays, and animal models may inform understanding of a GAS strain’s relative virulence, although none fully predict human disease patterns | CovR/S virulence regulator, wild type (nonmutant); does not bind plasminogen and fibrinogen; emm75 strains have been used in animal nasopharyngitis and invasive disease models |
Should have limited antibiotic resistance | Ideally, the challenge strain should be eradicated from the pharynx by antibiotic treatment; resistance to penicillin has not been documented in GAS, but it does not reliably eradicate GAS from the pharynx; observed resistance to other drugs is variable | See the text |
Challenge strain should possess a wide array of candidate vaccine antigens | For greatest impact, a GAS pharyngitis CHIM should be suitable for early use as a preliminary testing ground for vaccines | See the text |
See Table S1 for a detailed and referenced version of this table. ARF, acute rheumatic fever; APSGN, acute poststreptococcal glomerulonephritis; RHD, rheumatic heart disease.