Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model
Group A Streptococcus (GAS) is a major human pathogen for which there is no licensed vaccine. To protect against infection, a strong systemic and mucosal immune response is likely to be necessary to prevent initial colonization and any events that might lead to invasive disease. A broad immune respo...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/11/1724 |
| _version_ | 1797457562787905536 |
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| author | Helen Alexandra Shaw Alex Remmington Giselle McKenzie Caroline Winkel Fatme Mawas |
| author_facet | Helen Alexandra Shaw Alex Remmington Giselle McKenzie Caroline Winkel Fatme Mawas |
| author_sort | Helen Alexandra Shaw |
| collection | DOAJ |
| description | Group A Streptococcus (GAS) is a major human pathogen for which there is no licensed vaccine. To protect against infection, a strong systemic and mucosal immune response is likely to be necessary to prevent initial colonization and any events that might lead to invasive disease. A broad immune response will be necessary to target the varied GAS serotypes and disease presentations. To this end, we designed a representative panel of recombinant proteins to cover the stages of GAS infection and investigated whether mucosal and systemic immunity could be stimulated by these protein antigens. We immunized mice sublingually, intranasally and subcutaneously, then measured IgG and IgA antibody levels and functional activity through in vitro assays. Our results show that both sublingual and intranasal immunization in the presence of adjuvant induced both systemic IgG and mucosal IgA. Meanwhile, subcutaneous immunization generated only a serum IgG response. The antibodies mediated binding and killing of GAS cells and blocked binding of GAS to HaCaT cells, particularly following intranasal and subcutaneous immunizations. Further, antigen-specific assays revealed that immune sera inhibited cleavage of IL-8 by SpyCEP and IgG by Mac/IdeS. These results demonstrate that mucosal immunization can induce effective systemic and mucosal antibody responses. This finding warrants further investigation and optimization of humoral and cellular responses as a viable alternative to subcutaneous immunization for urgently needed GAS vaccines. |
| first_indexed | 2024-03-09T16:23:49Z |
| format | Article |
| id | doaj.art-9c42071cde8d46f995d85c15eff3b150 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T16:23:49Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-9c42071cde8d46f995d85c15eff3b1502023-11-24T15:10:18ZengMDPI AGVaccines2076-393X2023-11-011111172410.3390/vaccines11111724Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse ModelHelen Alexandra Shaw0Alex Remmington1Giselle McKenzie2Caroline Winkel3Fatme Mawas4Vaccines Division, Science, Research & Innovation, Medicines and Healthcare Products Regulatory Agency, Potters Bar EN6 3QG, UKVaccines Division, Science, Research & Innovation, Medicines and Healthcare Products Regulatory Agency, Potters Bar EN6 3QG, UKVaccines Division, Science, Research & Innovation, Medicines and Healthcare Products Regulatory Agency, Potters Bar EN6 3QG, UKVaccines Division, Science, Research & Innovation, Medicines and Healthcare Products Regulatory Agency, Potters Bar EN6 3QG, UKVaccines Division, Science, Research & Innovation, Medicines and Healthcare Products Regulatory Agency, Potters Bar EN6 3QG, UKGroup A Streptococcus (GAS) is a major human pathogen for which there is no licensed vaccine. To protect against infection, a strong systemic and mucosal immune response is likely to be necessary to prevent initial colonization and any events that might lead to invasive disease. A broad immune response will be necessary to target the varied GAS serotypes and disease presentations. To this end, we designed a representative panel of recombinant proteins to cover the stages of GAS infection and investigated whether mucosal and systemic immunity could be stimulated by these protein antigens. We immunized mice sublingually, intranasally and subcutaneously, then measured IgG and IgA antibody levels and functional activity through in vitro assays. Our results show that both sublingual and intranasal immunization in the presence of adjuvant induced both systemic IgG and mucosal IgA. Meanwhile, subcutaneous immunization generated only a serum IgG response. The antibodies mediated binding and killing of GAS cells and blocked binding of GAS to HaCaT cells, particularly following intranasal and subcutaneous immunizations. Further, antigen-specific assays revealed that immune sera inhibited cleavage of IL-8 by SpyCEP and IgG by Mac/IdeS. These results demonstrate that mucosal immunization can induce effective systemic and mucosal antibody responses. This finding warrants further investigation and optimization of humoral and cellular responses as a viable alternative to subcutaneous immunization for urgently needed GAS vaccines.https://www.mdpi.com/2076-393X/11/11/1724group A Streptococcusstrep A<i>Streptococcus pyogenes</i>vaccinesmulticomponentmucosal |
| spellingShingle | Helen Alexandra Shaw Alex Remmington Giselle McKenzie Caroline Winkel Fatme Mawas Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model Vaccines group A Streptococcus strep A <i>Streptococcus pyogenes</i> vaccines multicomponent mucosal |
| title | Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model |
| title_full | Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model |
| title_fullStr | Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model |
| title_full_unstemmed | Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model |
| title_short | Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model |
| title_sort | mucosal immunization has benefits over traditional subcutaneous immunization with group a streptococcus antigens in a pilot study in a mouse model |
| topic | group A Streptococcus strep A <i>Streptococcus pyogenes</i> vaccines multicomponent mucosal |
| url | https://www.mdpi.com/2076-393X/11/11/1724 |
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