Naturally acquired functional antibody responses to group A Streptococcus differ between major strain types
ABSTRACT Group A Streptococcus (GAS) is a leading human pathogen for which there is no licensed vaccine. Infections are most common in young children and the elderly suggesting immunity accumulates with exposure until immune senescence in older age. Though protection has been postulated to be strain...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2023-10-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00179-23 |
| _version_ | 1797651069250043904 |
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| author | Reuben McGregor Aimee Paterson Prachi Sharma Tiffany Chen Jarrod R. Lovell Lauren H. Carlton Andrew C. Steer Joshua Osowicki Jacelyn M. S. Loh Nicole J. Moreland |
| author_facet | Reuben McGregor Aimee Paterson Prachi Sharma Tiffany Chen Jarrod R. Lovell Lauren H. Carlton Andrew C. Steer Joshua Osowicki Jacelyn M. S. Loh Nicole J. Moreland |
| author_sort | Reuben McGregor |
| collection | DOAJ |
| description | ABSTRACT Group A Streptococcus (GAS) is a leading human pathogen for which there is no licensed vaccine. Infections are most common in young children and the elderly suggesting immunity accumulates with exposure until immune senescence in older age. Though protection has been postulated to be strain type specific, based on the M-protein (emm-type), the antigenic basis of population-level immunity remains poorly understood. Naturally acquired GAS antibody responses were investigated using intravenous immunoglobulin (IVIG), which contains pooled immunoglobulins from thousands of healthy human donors, as a surrogate for population immunity. Functional opsonophagocytic killing assays were conducted with GAS strains (n = 6) representing the three major emm-pattern types (emm12, A-C pattern; emm53, D-pattern; and emm75, E-pattern). While IVIG induced opsonophagocytic killing of all GAS strains tested, specificity assays showed the profile of protective antibodies differed considerably between emm-types. Antibodies targeting the M-protein were a major component of the functional IVIG antibody response for emm12 and emm53 strains but not for emm75 strains. The striking differences in the contribution of M-protein specific antibodies to killing suggest naturally acquired immunity differs between strains from the major emm-patterns. This challenges the dogma that M-protein is the primary protective antigen across all GAS straintypes. IMPORTANCE Group A Streptococcus (GAS) is a globally important pathogen. With the surge of invasive GAS infections that have occurred in multiple countries, contemporaneous with the relaxation of COVID-19 pandemic restrictions, there is increased interest in the mechanisms underpinning GAS immunity. We utilized intravenous immunoglobulin (IVIG), pooled immunoglobulins from thousands of healthy donors, as a surrogate for population-level immunity to GAS, and explored the contribution of strain-specific (M-type specific) antibodies to GAS immunity using functional killing assays. This revealed striking differences between major strain types as to the contribution of strain specific antibodies to killing. For GAS strains belonging to the E pattern group, M-type specific antibodies do not mediate killing and immunity, which contrasts with strains belonging to pattern A–C and D groups. This challenges the historical dogma, originally proposed by Rebecca Lancefield in the 1950–1960s, that the M-protein is the major protective antigen across all GAS strain types. |
| first_indexed | 2024-03-11T16:09:44Z |
| format | Article |
| id | doaj.art-e25b86a43fe942aa96e12a82aa053f80 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-03-11T16:09:44Z |
| publishDate | 2023-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-e25b86a43fe942aa96e12a82aa053f802023-10-24T16:32:15ZengAmerican Society for MicrobiologymSphere2379-50422023-10-018510.1128/msphere.00179-23Naturally acquired functional antibody responses to group A Streptococcus differ between major strain typesReuben McGregor0Aimee Paterson1Prachi Sharma2Tiffany Chen3Jarrod R. Lovell4Lauren H. Carlton5Andrew C. Steer6Joshua Osowicki7Jacelyn M. S. Loh8Nicole J. Moreland9School of Medical Science, Faculty of Medical and Health Sciences, The University of Auckland , Auckland, New ZealandSchool of Medical Science, Faculty of Medical and Health Sciences, The University of Auckland , Auckland, New ZealandSchool of Medical Science, Faculty of Medical and Health Sciences, The University of Auckland , Auckland, New ZealandSchool of Medical Science, Faculty of Medical and Health Sciences, The University of Auckland , Auckland, New ZealandSchool of Medical Science, Faculty of Medical and Health Sciences, The University of Auckland , Auckland, New ZealandSchool of Medical Science, Faculty of Medical and Health Sciences, The University of Auckland , Auckland, New ZealandTropical Diseases Research Group, Murdoch Children’s Research Institute , Melbourne, Victoria, AustraliaTropical Diseases Research Group, Murdoch Children’s Research Institute , Melbourne, Victoria, AustraliaSchool of Medical Science, Faculty of Medical and Health Sciences, The University of Auckland , Auckland, New ZealandSchool of Medical Science, Faculty of Medical and Health Sciences, The University of Auckland , Auckland, New ZealandABSTRACT Group A Streptococcus (GAS) is a leading human pathogen for which there is no licensed vaccine. Infections are most common in young children and the elderly suggesting immunity accumulates with exposure until immune senescence in older age. Though protection has been postulated to be strain type specific, based on the M-protein (emm-type), the antigenic basis of population-level immunity remains poorly understood. Naturally acquired GAS antibody responses were investigated using intravenous immunoglobulin (IVIG), which contains pooled immunoglobulins from thousands of healthy human donors, as a surrogate for population immunity. Functional opsonophagocytic killing assays were conducted with GAS strains (n = 6) representing the three major emm-pattern types (emm12, A-C pattern; emm53, D-pattern; and emm75, E-pattern). While IVIG induced opsonophagocytic killing of all GAS strains tested, specificity assays showed the profile of protective antibodies differed considerably between emm-types. Antibodies targeting the M-protein were a major component of the functional IVIG antibody response for emm12 and emm53 strains but not for emm75 strains. The striking differences in the contribution of M-protein specific antibodies to killing suggest naturally acquired immunity differs between strains from the major emm-patterns. This challenges the dogma that M-protein is the primary protective antigen across all GAS straintypes. IMPORTANCE Group A Streptococcus (GAS) is a globally important pathogen. With the surge of invasive GAS infections that have occurred in multiple countries, contemporaneous with the relaxation of COVID-19 pandemic restrictions, there is increased interest in the mechanisms underpinning GAS immunity. We utilized intravenous immunoglobulin (IVIG), pooled immunoglobulins from thousands of healthy donors, as a surrogate for population-level immunity to GAS, and explored the contribution of strain-specific (M-type specific) antibodies to GAS immunity using functional killing assays. This revealed striking differences between major strain types as to the contribution of strain specific antibodies to killing. For GAS strains belonging to the E pattern group, M-type specific antibodies do not mediate killing and immunity, which contrasts with strains belonging to pattern A–C and D groups. This challenges the historical dogma, originally proposed by Rebecca Lancefield in the 1950–1960s, that the M-protein is the major protective antigen across all GAS strain types.https://journals.asm.org/doi/10.1128/msphere.00179-23group A StreptococcusM-typeimmunityopsonophagocytosisantibodyhuman |
| spellingShingle | Reuben McGregor Aimee Paterson Prachi Sharma Tiffany Chen Jarrod R. Lovell Lauren H. Carlton Andrew C. Steer Joshua Osowicki Jacelyn M. S. Loh Nicole J. Moreland Naturally acquired functional antibody responses to group A Streptococcus differ between major strain types mSphere group A Streptococcus M-type immunity opsonophagocytosis antibody human |
| title | Naturally acquired functional antibody responses to group A Streptococcus differ between major strain types |
| title_full | Naturally acquired functional antibody responses to group A Streptococcus differ between major strain types |
| title_fullStr | Naturally acquired functional antibody responses to group A Streptococcus differ between major strain types |
| title_full_unstemmed | Naturally acquired functional antibody responses to group A Streptococcus differ between major strain types |
| title_short | Naturally acquired functional antibody responses to group A Streptococcus differ between major strain types |
| title_sort | naturally acquired functional antibody responses to group a streptococcus differ between major strain types |
| topic | group A Streptococcus M-type immunity opsonophagocytosis antibody human |
| url | https://journals.asm.org/doi/10.1128/msphere.00179-23 |
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