Protective efficacy of PspA (pneumococcal surface protein A)-based DNA vaccines: contribution of both humoral and cellular immune responses
| Autor: | E. N. Miyaji, Waldely O. Dias, Martha M. Tanizaki, Luciana C. C. Leite |
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| Rok vydání: | 2003 |
| Předmět: |
Microbiology (medical)
Cellular immunity Cost effectiveness Immunology medicine.disease_cause Microbiology Pneumococcal Infections DNA vaccination Pneumococcal Vaccines Mice Immune system Antigen Bacterial Proteins Phagocytosis Streptococcus pneumoniae medicine Vaccines DNA Immunology and Allergy Animals Mice Inbred BALB C biology General Medicine Opsonin Proteins Th1 Cells Antibodies Bacterial Infectious Diseases Humoral immunity biology.protein Female Immunization Antibody |
| Zdroj: | FEMS immunology and medical microbiology. 37(1) |
| ISSN: | 0928-8244 |
| Popis: | Streptococcus pneumoniae is a major public health problem and new strategies for the development of cost-effective alternative vaccines are important. The use of protein antigens such as PspA (pneumococcal surface protein A) is a promising approach to increase coverage at reduced costs. We have previously described the induction of a strong antibody response by a DNA vaccine expressing a C-terminal fragment of PspA. Fusion of this fragment with the cytoplasmic variant of SV40 large T-antigen (CT-Ag) caused reduction in specific interferon-gamma produced by stimulated spleen cells. In this work we show that the DNA vaccine expressing the C-terminal region of PspA elicits significant protection in mice against intraperitoneal challenge with a virulent strain of S. pneumoniae. Furthermore, fusion with CT-Ag completely abrogated the protection elicited by DNA immunization with this fragment. In this case, protection did not correlate with total anti-PspA antibody production nor with total IgG2a levels. The anti-PspA sera obtained from both constructs showed equivalent opsonic activity of pneumococci, indicating that the antibodies produced were functional. We could, though, observe a correlation between a lower IgG1:IgG2a ratio, which is indicative of a stronger bias towards Th1 responses, and protection. We also show that a vector expressing the most variable N-terminal alpha-helical region induces higher antibody formation, with increased protection of mice against intraperitoneal challenge with a more virulent strain of S. pneumoniae. As a whole, these results indicate that antibodies elicited against PspA would not be solely responsible for the protection induced by DNA vaccination and that cell-mediated immune responses could also be involved in protection against pneumococcal sepsis. |
| Databáze: | OpenAIRE |
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