Conjugation of PspA4Pro with Capsular Streptococcus pneumoniae Polysaccharide Serotype 14 Does Not Reduce the Induction of Cross-Reactive Antibodies
| Autor: | Giovana Cappio Barazzone, Martha M. Tanizaki, Luciana C. C. Leite, T.R. Converso, Viviane Maimoni Gonçalves, Miriam A. Silva |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Serotype 030106 microbiology Clinical Biochemistry Immunology Cross Reactions Biology Serogroup medicine.disease_cause Pneumococcal Infections Microbiology Pneumococcal Vaccines Mice 03 medical and health sciences Bacterial Proteins Antigen Conjugate vaccine Streptococcus pneumoniae medicine Animals Immunology and Allergy Mice Inbred BALB C Vaccines Vaccines Conjugate Polysaccharides Bacterial Vaccination Bacterial polysaccharide medicine.disease Antibodies Bacterial Pneumococcal infections Pneumococcal vaccine Immunoglobulin G |
| Zdroj: | Clinical and Vaccine Immunology. 24 |
| ISSN: | 1556-679X 1556-6811 |
| DOI: | 10.1128/cvi.00118-17 |
| Popis: | Current pneumococcal vaccines are composed of bacterial polysaccharides as antigens, plain or conjugated to carrier proteins. While efficacious against vaccine serotypes, epidemiologic data show an increasing incidence of infections caused by nonvaccine serotypes ofStreptococcus pneumoniae. The use of pneumococcal surface protein A (PspA) as a carrier protein in a conjugate vaccine could help prevent serotype replacement by increasing vaccine coverage and reducing selective pressure ofS. pneumoniaeserotypes. PspA is present in all pneumococcal strains, is highly immunogenic, and is known to induce protective antibodies. Based on its sequence, PspA has been classified into three families and six clades. A PspA fragment derived from family 2, clade 4 (PspA4Pro), was shown to generate antibodies with a broad range of cross-reactivity, across clades and families. Here, PspA4Pro was modified and conjugated to capsular polysaccharide serotype 14 (PS14). We investigated the impact of conjugation on the immune response induced to PspA4Pro and PS14. Mice immunized with the PS14-mPspA4Pro conjugate produced higher titers of anti-PS14 antibodies than the animals that received coadministered antigens. The conjugate induced antibodies with opsonophagocytic activity against PS14-carrying strains, as well as against a panel of strains bearing PspAs from five clades (encompassing families 1 and 2) bearing a non-PS14 serotype. Furthermore, mice immunized with PS14-mPspA4Pro were protected against nasal colonization with a nonrelatedS. pneumoniaestrain bearing PspA from clade 1, serotype 6B. These results demonstrate that the cross-reactivity mediated by PspA4Pro is retained following conjugation, supporting the use of PspA4 as a carrier protein in order to enhance pneumococcal vaccine coverage and encourage its further investigation as a candidate in future vaccine designs. |
| Databáze: | OpenAIRE |
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