Vaccine-induced, but not natural immunity, against the Streptococcal inhibitor of complement protects against invasive disease

Lionel K. K. Tan, Mark Reglinski, Daryl Teo, Nada Reza, Lucy E. M. Lamb, Vaitehi Nageshwaran, Claire E. Turner, Mats Wikstrom, Inga-Maria Frick, Lars Bjorck, Shiranee Sriskandan (Lead / Corresponding author)

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Abstract

Highly pathogenic emm1 Streptococcus pyogenes strains secrete the multidomain Streptococcal inhibitor of complement (SIC) that binds and inactivates components of the innate immune response. We aimed to determine if naturally occurring or vaccine-induced antibodies to SIC are protective against invasive S. pyogenes infection. Immunisation with full-length SIC protected mice against systemic bacterial dissemination following intranasal or intramuscular infection with emm1 S. pyogenes. Vaccine-induced rabbit anti-SIC antibodies, but not naturally occurring human anti-SIC antibodies, enhanced bacterial clearance in an ex vivo whole-blood assay. SIC vaccination of both mice and rabbits resulted in antibody recognition of all domains of SIC, whereas naturally occurring human anti-SIC antibodies recognised the proline-rich region of SIC only. We, therefore, propose a model whereby natural infection with S. pyogenes generates non-protective antibodies against the proline-rich region of SIC, while vaccination with full-length SIC permits the development of protective antibodies against all SIC domains.

Original languageEnglish
Article number62
Number of pages9
JournalNPJ Vaccines
Volume6
DOIs
Publication statusPublished - 22 Apr 2021

Keywords

  • Immunology
  • Medical research
  • Microbiology
  • Pathogenesis

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