# NIH grant: Discovery of Group A Streptococcus antigens for development of broadly effective vaccine candidates to prevent non-invasive and invasive disease and emergence of antimicrobial resistance (1R43AI192098-01A1) — retained record

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NIH grant 1R43AI192098-01A1: Discovery of Group A Streptococcus antigens for development of broadly effective vaccine candidates to prevent non-invasive and invasive disease and emergence of antimicrobial resistance
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Joseph J. Campo. Award: $300000.
Start: 2026-08-26T00:00:00.
Streptococcus pyogenes is a Gram-positive extracellular bacterium (Group A Streptococcus, or “GAS”) that is exclusively
pathogenic in humans and can cause non-invasive infections such as pharyngitis, tonsillitis, impetigo, and pyoderma, as
well as outbreaks of scarlet fever. This can advance to invasive GAS infections that occult blood stream infections,
pneumonia, necrotizing skin and soft tissue infection, myositis, and puerperal sepsis, all of which can be complicated by
streptococcal toxic shock syndrome. Non-invasive GAS infections such as pharyngitis and pyoderma are associated with a
concomitant high prevalence of auto-immune sequelae such as acute rheumatic fever which can lead to rheumatic heart
disease. GAS causes significant morbidity, mortality and socioeconomic costs globally, with low- and middle-income
countries (LMIC) bearing the greatest burden. A broadly effective vaccine against non-invasive forms of infection would
theoretically reduce or even eradicate all types of GAS disease, including rheumatic fever and invasive infection. There is
currently an urgent need for a GAS vaccine, as health authorities are on alert in multiple countries about scarlet fever and
invasive GAS disease on the rise following the SARS-CoV-2 pandemic. A GAS vaccine is possible, as evidenced by the
acquisition of immunity to GAS disease in early life and persisting until old age. Vaccine development efforts have focused
on a small selection of proteins encoded by the >1,300 S. pyogenes core genes, thus most of the S. pyogenes genome remains
unexplored for vaccine candidates. A proteome-wide screening tool such as the pangenomic protein microarray technology
developed by Antigen Discovery, Inc. (ADI) of Irvine, California would be an important advance in GAS vaccinology and
facilitate discovery of novel vaccine candidates. ADI, in collaboration with Prof. Shiranee Sriskandan of Imperial College
London, Prof. Thushan de Silva at MRC Unit The Gambia and members of the Immunity to Streptococcus pyogenes
Network (iSpy-Net), will develop and test a S. pyogenes panproteome microarray with up to 1,000 S. pyogenes proteins for
discovery of protein targets of antibodies in young children (presumed non-immune) and adults (presumed immune) from
diverse populations in the UK and The Gambia, as well as in classroom cases and contacts of GAS diseases. Both systemic
and mucosal antibody responses will be measured in serum and gingival crevicular fluid, respectively, for IgG and IgA
binding to S. pyogenes proteins. After examining antibody profiles associated with age-related acquisition of immunity, and
after excluding potential autoimmunity-inducing antigens by assessing specific GAS antigen-binding antibodies on human
proteome microarrays containing ~21,000 human proteins, we will develop antigen-specific functional assays to detect
antibody-dependent complement activation and opsonophagocytosis based on new technology for in vitro protein
expression and immobilization (IVPEI) onto functionalized magnetic microspheres using ADI’s expansive cell-free
expression clone libraries, and we will characterize antibody function in these study samples. Our future aims for an SBIR
Phase 2 application are to validate and further characterize antibody function in a longitudinal study of children and adults
with defined GAS infection status, and to establish novel vaccine candidate antigens.
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