Background
In 1796, Erasmus Darwin (Charles’ grandfather) pointed to scarlet fever as the next immunisation target after smallpox. While the profile of Streptococcus pyogenes disease is different today, the pathogen still kills more than 500,000 annually. It is often cited that despite over a century of efforts, there is no licensed vaccine for S. pyogenes. We aimed to review the results of previous efforts and lessons for modern S. pyogenes vaccine development initiatives.
Methods
Database search without date or language restrictions, and subsequent screening of reference lists. Abstracts and full-text articles were retrieved, and key data extracted: number vaccinated and unvaccinated; vaccine details; clinical, immunogenicity, and safety results.
Results
140 publications were included, from 1906 to 2020. Incredibly, S. pyogenes vaccines have been administered to more than 200,000 individuals, predominantly children in the USA and USSR. The peak of vaccination was in the 1920s and 1930s, with formulations pioneered by Georg Gabritschewsky (heat-killed bacteria) and George and Gladys Dick (filtered culture supernatant). Primary outcomes included: disease incidence, ‘Dick test’ conversion (toxin-based intradermal test), and laboratory immunoassays. In trials and public campaigns, reported efficacy was typically greater than 70%. Among reported adverse events following immunisation, brief systemic inflammatory responses were most common, followed by local reactions, and 3 cases of acute rheumatic fever in one 1969 report.
Conclusion
The colourful history of S. pyogenes vaccination should offer encouragement to modern vaccine developers that a safe and effective product is a realistic prospect. These studies can also inform how we understand protective immunity against this important pathogen.