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Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies

de Neergaard, Therese LU ; Bläckberg, Anna LU ; Ivarsson, Hanna ; Thomasson, Sofia ; Kumra Ahnlide, Vibha LU ; Chowdhury, Sounak LU ; Khakzad, Hamed ; Bahnan, Wael LU ; Malmström, Johan LU orcid and Rasmussen, Magnus LU , et al. (2022) In Microbiology spectrum 10(6).
Abstract

The human pathogen Streptococcus pyogenes causes substantial morbidity and mortality. It is unclear if antibodies developed after infections with this pathogen are opsonic and if they are strain specific or more broadly protective. Here, we quantified the opsonic-antibody response following invasive S. pyogenes infection. Four patients with S. pyogenes bacteremia between 2018 and 2020 at Skåne University Hospital in Lund, Sweden, were prospectively enrolled. Acute- and convalescent-phase sera were obtained, and the S. pyogenes isolates were genome sequenced (
emm118,
emm85, and two
emm1 isolates). Quantitative antibody binding and phagocytosis assays were used to evaluate isolate-dependent opsonic antibody function in... (More)

The human pathogen Streptococcus pyogenes causes substantial morbidity and mortality. It is unclear if antibodies developed after infections with this pathogen are opsonic and if they are strain specific or more broadly protective. Here, we quantified the opsonic-antibody response following invasive S. pyogenes infection. Four patients with S. pyogenes bacteremia between 2018 and 2020 at Skåne University Hospital in Lund, Sweden, were prospectively enrolled. Acute- and convalescent-phase sera were obtained, and the S. pyogenes isolates were genome sequenced (
emm118,
emm85, and two
emm1 isolates). Quantitative antibody binding and phagocytosis assays were used to evaluate isolate-dependent opsonic antibody function in response to infection. Antibody binding increased modestly against the infecting isolate and across
emm types in convalescent- compared to acute-phase sera for all patients. For two patients, phagocytosis increased in convalescent-phase serum both for the infecting isolate and across types. The increase was only across types for one patient, and one had no improvement. No correlation to the clinical outcomes was observed. Invasive S. pyogenes infections result in a modestly increased antibody binding with differential opsonic capacity, both nonfunctional binding and broadly opsonic binding across types. These findings question the dogma that an invasive infection should lead to a strong type-specific antibody increase rather than a more modest but broadly reactive response, as seen in these patients. Furthermore, our results indicate that an increase in antibody titers might not be indicative of an opsonic response and highlight the importance of evaluating antibody function in S. pyogenes infections.
IMPORTANCE The bacterium Streptococcus pyogenes is a common cause of both mild and severe human diseases resulting in substantial morbidity and mortality each year. No vaccines are available, and our understanding of the antibody response to this human pathogen is still incomplete. Here, we carefully analyzed the opsonic antibody response following invasive infection in four patients. Unexpectedly, the patients did not always generate opsonic antibodies against the specific infecting strain. Instead, we found that some patients could generate cross-opsonic antibodies, leading to phagocytosis of bacteria across strains. The emergence of cross-opsonic antibodies is likely important for long-term immunity against S. pyogenes. Our findings question the dogma that mostly strain-specific immunity is developed after infection and add to our overall understanding of how immunity to S. pyogenes can evolve.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Microbiology spectrum
volume
10
issue
6
article number
e0248622
publisher
American Society for Microbiology
external identifiers
  • pmid:36314947
  • scopus:85144635535
ISSN
2165-0497
DOI
10.1128/spectrum.02486-22
language
English
LU publication?
yes
id
53afec1f-49c4-43e5-b200-f4342e54bbb0
date added to LUP
2022-11-07 08:21:46
date last changed
2024-06-27 21:55:28
@article{53afec1f-49c4-43e5-b200-f4342e54bbb0,
  abstract     = {{<p>The human pathogen Streptococcus pyogenes causes substantial morbidity and mortality. It is unclear if antibodies developed after infections with this pathogen are opsonic and if they are strain specific or more broadly protective. Here, we quantified the opsonic-antibody response following invasive S. pyogenes infection. Four patients with S. pyogenes bacteremia between 2018 and 2020 at Skåne University Hospital in Lund, Sweden, were prospectively enrolled. Acute- and convalescent-phase sera were obtained, and the S. pyogenes isolates were genome sequenced (<br>
 emm118, <br>
 emm85, and two <br>
 emm1 isolates). Quantitative antibody binding and phagocytosis assays were used to evaluate isolate-dependent opsonic antibody function in response to infection. Antibody binding increased modestly against the infecting isolate and across <br>
 emm types in convalescent- compared to acute-phase sera for all patients. For two patients, phagocytosis increased in convalescent-phase serum both for the infecting isolate and across types. The increase was only across types for one patient, and one had no improvement. No correlation to the clinical outcomes was observed. Invasive S. pyogenes infections result in a modestly increased antibody binding with differential opsonic capacity, both nonfunctional binding and broadly opsonic binding across types. These findings question the dogma that an invasive infection should lead to a strong type-specific antibody increase rather than a more modest but broadly reactive response, as seen in these patients. Furthermore, our results indicate that an increase in antibody titers might not be indicative of an opsonic response and highlight the importance of evaluating antibody function in S. pyogenes infections. <br>
 IMPORTANCE The bacterium Streptococcus pyogenes is a common cause of both mild and severe human diseases resulting in substantial morbidity and mortality each year. No vaccines are available, and our understanding of the antibody response to this human pathogen is still incomplete. Here, we carefully analyzed the opsonic antibody response following invasive infection in four patients. Unexpectedly, the patients did not always generate opsonic antibodies against the specific infecting strain. Instead, we found that some patients could generate cross-opsonic antibodies, leading to phagocytosis of bacteria across strains. The emergence of cross-opsonic antibodies is likely important for long-term immunity against S. pyogenes. Our findings question the dogma that mostly strain-specific immunity is developed after infection and add to our overall understanding of how immunity to S. pyogenes can evolve.<br>
 </p>}},
  author       = {{de Neergaard, Therese and Bläckberg, Anna and Ivarsson, Hanna and Thomasson, Sofia and Kumra Ahnlide, Vibha and Chowdhury, Sounak and Khakzad, Hamed and Bahnan, Wael and Malmström, Johan and Rasmussen, Magnus and Nordenfelt, Pontus}},
  issn         = {{2165-0497}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{6}},
  publisher    = {{American Society for Microbiology}},
  series       = {{Microbiology spectrum}},
  title        = {{Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies}},
  url          = {{http://dx.doi.org/10.1128/spectrum.02486-22}},
  doi          = {{10.1128/spectrum.02486-22}},
  volume       = {{10}},
  year         = {{2022}},
}