Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2022-12-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02486-22 |
| _version_ | 1811290091535990784 |
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| author | Therese de Neergaard Anna Bläckberg Hanna Ivarsson Sofia Thomasson Vibha Kumra Ahnlide Sounak Chowdhury Hamed Khakzad Wael Bahnan Johan Malmström Magnus Rasmussen Pontus Nordenfelt |
| author_facet | Therese de Neergaard Anna Bläckberg Hanna Ivarsson Sofia Thomasson Vibha Kumra Ahnlide Sounak Chowdhury Hamed Khakzad Wael Bahnan Johan Malmström Magnus Rasmussen Pontus Nordenfelt |
| author_sort | Therese de Neergaard |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-04-13T04:06:42Z |
| format | Article |
| id | doaj.art-88ea6ae07644475ba144a4b946cc7bf8 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-13T04:06:42Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-88ea6ae07644475ba144a4b946cc7bf82022-12-22T03:03:14ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-12-0110610.1128/spectrum.02486-22Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic AntibodiesTherese de Neergaard0Anna Bläckberg1Hanna Ivarsson2Sofia Thomasson3Vibha Kumra Ahnlide4Sounak Chowdhury5Hamed Khakzad6Wael Bahnan7Johan Malmström8Magnus Rasmussen9Pontus Nordenfelt10Division of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, SwedenDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, SwedenDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, SwedenDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, SwedenDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, SwedenDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, SwedenLaboratory of Protein Design and Immunoengineering, STI, EPFL, Lausanne, SwitzerlandDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, SwedenDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, SwedenDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, SwedenDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, SwedenABSTRACT 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.https://journals.asm.org/doi/10.1128/spectrum.02486-22Streptococcus pyogenesemm typeantibody responsephagocytosisbacteremiaantibody function |
| spellingShingle | Therese de Neergaard Anna Bläckberg Hanna Ivarsson Sofia Thomasson Vibha Kumra Ahnlide Sounak Chowdhury Hamed Khakzad Wael Bahnan Johan Malmström Magnus Rasmussen Pontus Nordenfelt Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies Microbiology Spectrum Streptococcus pyogenes emm type antibody response phagocytosis bacteremia antibody function |
| title | Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies |
| title_full | Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies |
| title_fullStr | Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies |
| title_full_unstemmed | Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies |
| title_short | Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies |
| title_sort | invasive streptococcal infection can lead to the generation of cross strain opsonic antibodies |
| topic | Streptococcus pyogenes emm type antibody response phagocytosis bacteremia antibody function |
| url | https://journals.asm.org/doi/10.1128/spectrum.02486-22 |
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