Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) in healthy Japanese adults
A novel Staphylococcus aureus 4-antigen vaccine (SA4Ag) is under development, comprising capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM197, recombinant protein clumping factor A (rmClfA), and recombinant manganese transporter protein C (MntC). We evaluated SA4Ag safety, to...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-11-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2018.1496764 |
| _version_ | 1797677470557667328 |
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| author | Megumi Inoue Takuma Yonemura James Baber Yasuko Shoji Masakazu Aizawa David Cooper Joseph Eiden William C. Gruber Kathrin U. Jansen Annaliesa S. Anderson Alejandra Gurtman |
| author_facet | Megumi Inoue Takuma Yonemura James Baber Yasuko Shoji Masakazu Aizawa David Cooper Joseph Eiden William C. Gruber Kathrin U. Jansen Annaliesa S. Anderson Alejandra Gurtman |
| author_sort | Megumi Inoue |
| collection | DOAJ |
| description | A novel Staphylococcus aureus 4-antigen vaccine (SA4Ag) is under development, comprising capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM197, recombinant protein clumping factor A (rmClfA), and recombinant manganese transporter protein C (MntC). We evaluated SA4Ag safety, tolerability, and immunogenicity in Japanese adults aged 20 to 64 and 65 to 85 years. A total of 136 healthy Japanese adults (68 per age group) were randomized 1:1 to receive single-dose SA4Ag or placebo intramuscularly (Day 1). Safety assessments included reactogenicity and adverse events. The ability of the vaccine to induce immune responses that are considered functional due to their ability to facilitate the killing of S. aureus or neutralize S. aureus virulence mechanisms was assessed using 5 different antigen-specific assays. SA4Ag was well tolerated in both age groups, with no safety concerns. At Day 29, > 85% of SA4Ag recipients in each age group achieved predefined thresholds for each antigen. Antibody geometric mean-fold rises from baseline to Day 29 in SA4Ag groups were: > 80 and > 30 for CP5 and CP8 (opsonophagocytic activity assay), > 10 for ClfA (fibrinogen-binding inhibition assay), and > 15 and > 7 for ClfA and MntC (competitive Luminex® immunoassay), respectively. Antibody titers decreased through Month 12 but remained well above baseline and placebo levels. SA4Ag had an acceptable safety profile and induced rapid and robust functional immune responses in both age groups. These results support ongoing development of SA4Ag for the prevention of invasive S. aureus disease in elective-surgery patients in Japan, North America, and Europe. |
| first_indexed | 2024-03-11T22:45:37Z |
| format | Article |
| id | doaj.art-481dcce04a3a42e8ba5c60e3af8591d6 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:45:37Z |
| publishDate | 2018-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-481dcce04a3a42e8ba5c60e3af8591d62023-09-22T08:38:22ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2018-11-0114112682269110.1080/21645515.2018.14967641496764Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) in healthy Japanese adultsMegumi Inoue0Takuma Yonemura1James Baber2Yasuko Shoji3Masakazu Aizawa4David Cooper5Joseph Eiden6William C. Gruber7Kathrin U. Jansen8Annaliesa S. Anderson9Alejandra Gurtman10SOUSEIKAI PS ClinicSOUSEIKAI Sumida HospitalPfizer Vaccine Research and DevelopmentPfizer Vaccine Research and DevelopmentPfizer Vaccine Research and DevelopmentPfizer Vaccine Research and DevelopmentPfizer Vaccine Research and DevelopmentPfizer Vaccine Research and DevelopmentPfizer Vaccine Research and DevelopmentPfizer Vaccine Research and DevelopmentPfizer Vaccine Research and DevelopmentA novel Staphylococcus aureus 4-antigen vaccine (SA4Ag) is under development, comprising capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM197, recombinant protein clumping factor A (rmClfA), and recombinant manganese transporter protein C (MntC). We evaluated SA4Ag safety, tolerability, and immunogenicity in Japanese adults aged 20 to 64 and 65 to 85 years. A total of 136 healthy Japanese adults (68 per age group) were randomized 1:1 to receive single-dose SA4Ag or placebo intramuscularly (Day 1). Safety assessments included reactogenicity and adverse events. The ability of the vaccine to induce immune responses that are considered functional due to their ability to facilitate the killing of S. aureus or neutralize S. aureus virulence mechanisms was assessed using 5 different antigen-specific assays. SA4Ag was well tolerated in both age groups, with no safety concerns. At Day 29, > 85% of SA4Ag recipients in each age group achieved predefined thresholds for each antigen. Antibody geometric mean-fold rises from baseline to Day 29 in SA4Ag groups were: > 80 and > 30 for CP5 and CP8 (opsonophagocytic activity assay), > 10 for ClfA (fibrinogen-binding inhibition assay), and > 15 and > 7 for ClfA and MntC (competitive Luminex® immunoassay), respectively. Antibody titers decreased through Month 12 but remained well above baseline and placebo levels. SA4Ag had an acceptable safety profile and induced rapid and robust functional immune responses in both age groups. These results support ongoing development of SA4Ag for the prevention of invasive S. aureus disease in elective-surgery patients in Japan, North America, and Europe.http://dx.doi.org/10.1080/21645515.2018.1496764capsular polysaccharideclumping factor afunctional antibodiesmanganese transporter cstaphylococcus aureusvaccine |
| spellingShingle | Megumi Inoue Takuma Yonemura James Baber Yasuko Shoji Masakazu Aizawa David Cooper Joseph Eiden William C. Gruber Kathrin U. Jansen Annaliesa S. Anderson Alejandra Gurtman Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) in healthy Japanese adults Human Vaccines & Immunotherapeutics capsular polysaccharide clumping factor a functional antibodies manganese transporter c staphylococcus aureus vaccine |
| title | Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) in healthy Japanese adults |
| title_full | Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) in healthy Japanese adults |
| title_fullStr | Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) in healthy Japanese adults |
| title_full_unstemmed | Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) in healthy Japanese adults |
| title_short | Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) in healthy Japanese adults |
| title_sort | safety tolerability and immunogenicity of a novel 4 antigen staphylococcus aureus vaccine sa4ag in healthy japanese adults |
| topic | capsular polysaccharide clumping factor a functional antibodies manganese transporter c staphylococcus aureus vaccine |
| url | http://dx.doi.org/10.1080/21645515.2018.1496764 |
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