title: Protective efficacy of PspA (pneumococcal surface protein A)-based DNA vaccines: contribution of both humoral and cellular immune responses.
abstract: 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.
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Av Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil. enmiyaji@uol.com.br
authors.forename: Eliane N
authors.initials: EN
authors.lastname: Miyaji
authors.forename: Waldely O
authors.initials: WO
authors.lastname: Dias
authors.forename: Martha M
authors.initials: MM
authors.lastname: Tanizaki
authors.forename: Luciana C C
authors.initials: LC
authors.lastname: Leite
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009895:Opsonin Proteins; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D009895:Opsonin Proteins; D022242:Pneumococcal Vaccines; D019444:Vaccines, DNA; C051592:pneumococcal surface protein A