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

Tan, Lionel K.K. ; Reglinski, Mark ; Teo, Daryl ; Reza, Nada ; Lamb, Lucy E.M. ; Nageshwaran, Vaitehi ; Turner, Claire E. ; Wikstrom, Mats ; Frick, Inga Maria LU and Bjorck, Lars LU , et al. (2021) In npj Vaccines 6.
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,... (More)

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.

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type
Contribution to journal
publication status
published
subject
in
npj Vaccines
volume
6
article number
62
publisher
Nature Publishing Group
external identifiers
  • scopus:85104578759
  • pmid:33888727
ISSN
2059-0105
DOI
10.1038/s41541-021-00326-3
language
English
LU publication?
yes
id
a51e6d3d-a29a-4a45-b75e-9ebc63755e91
date added to LUP
2021-05-04 16:43:37
date last changed
2021-05-05 07:12:58
@article{a51e6d3d-a29a-4a45-b75e-9ebc63755e91,
  abstract     = {<p>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.</p>},
  author       = {Tan, Lionel K.K. and Reglinski, Mark and Teo, Daryl and Reza, Nada and Lamb, Lucy E.M. and Nageshwaran, Vaitehi and Turner, Claire E. and Wikstrom, Mats and Frick, Inga Maria and Bjorck, Lars and Sriskandan, Shiranee},
  issn         = {2059-0105},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {npj Vaccines},
  title        = {Vaccine-induced, but not natural immunity, against the Streptococcal inhibitor of complement protects against invasive disease},
  url          = {http://dx.doi.org/10.1038/s41541-021-00326-3},
  doi          = {10.1038/s41541-021-00326-3},
  volume       = {6},
  year         = {2021},
}