Optimized immune response elicited by a DNA vaccine expressing pneumococcal surface protein a is characterized by a balanced immunoglobulin G1 (IgG1)/IgG2a ratio and proinflammatory cytokine production.
We have previously shown that DNA immunization with PspA (pneumococcal surface protein A) DNA is able to elicit protection comparable to that elicited by immunization with PspA protein (with alum as adjuvant), even though the antibody levels elicited by DNA immunization are lower than those elicited by immunization with the protein. This work aims at characterizing the ability of sera to bind to the pneumococcal surface and to mediate complement deposition, using BALB/c wild-type and interleukin-4 knockout mice. We observed that higher anti-PspA levels correlated with intense antibody binding to the pneumococcal surface, while elevated complement deposition was observed with sera that presented balanced immunoglobulin G1 (IgG1)/IgG2a ratios, such as those from DNA-immunized mice. Furthermore, we demonstrated that gamma interferon and tumor necrosis factor alpha were strongly induced after intraperitoneal pneumococcal challenge only in mice immunized with the DNA vaccine. We therefore postulate that although both DNA and recombinant protein immunizations are able to protect mice against intraperitoneal pneumococcal challenge, an optimized response would be achieved by using a DNA vaccine and other strategies capable of inducing balanced Th1/Th2 responses.
Ferreira
Daniela M
DM
Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil.
Darrieux
Michelle
M
Oliveira
Maria Leonor S
ML
Leite
Luciana C C
LC
Miyaji
Eliane N
EN
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; C051592:pneumococcal surface protein A; D015847:Interleukin-4; D007371:Interferon-gamma