DNA vaccines expressing pneumococcal surface protein A (PspA) elicit protection levels comparable to recombinant protein

Pneumococcal surface protein A (PspA) is a promising candidate for the development of cost-effective vaccines against Streptococcus pneumoniae. In the present study, BALB/c mice were immunized with DNA vaccine vectors expressing the N-terminal region of PspA. Animals immunized with a vector expressing secreted PspA developed higher levels of antibody than mice immunized with the vector expressing the antigen in the cytosol. However, both immunogens elicited similar levels of protection against intraperitoneal challenge. Furthermore, immunization with exactly the same fragment in the form of a recombinant protein, with aluminium hydroxide as an adjuvant, elicited even higher antibody levels, but this increased humoral response did not correlate with enhanced protection. These results show that DNA vaccines expressing PspA are able to elicit protection levels comparable to recombinant protein, even though total anti-PspA IgG response is considerably lower.

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Characterization of the antibody response elicited by immunization with pneumococcal surface protein A (PspA) as recombinant protein or DNA vaccine and analysis of protection against an intranasal lethal challenge with Streptococcus pneumoniae

Microbial Pathogenesis ◽

10.1016/j.micpath.2012.08.007 ◽

2012 ◽

Vol 53 (5-6) ◽

pp. 243-249 ◽

Cited By ~ 16

Author(s):

Cintia F.M. Vadesilho ◽

Daniela M. Ferreira ◽

Adriana T. Moreno ◽

Carlos Chavez-Olortegui ◽

Ricardo A. Machado de Avila ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Recombinant Protein ◽

Antibody Response ◽

Dna Vaccine ◽

Protein A ◽

Surface Protein ◽

Lethal Challenge ◽

Pneumococcal Surface Protein A

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PsaA (pneumococcal surface adhesin A) and PspA (pneumococcal surface protein A) DNA vaccines induce humoral and cellular immune responses against Streptococcus pneumoniae

Vaccine ◽

10.1016/s0264-410x(01)00395-4 ◽

2001 ◽

Vol 20 (5-6) ◽

pp. 805-812 ◽

Cited By ~ 33

Author(s):

Eliane N. Miyaji ◽

Waldely O. Dias ◽

Márcia Gamberini ◽

Vera C.B.C. Gebara ◽

Rocilda P.F. Schenkman ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Immune Responses ◽

Dna Vaccines ◽

Protein A ◽

Surface Protein ◽

Cellular Immune Responses ◽

Pneumococcal Surface Protein A ◽

Cellular Immune

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Analysis of Serum Cross-Reactivity and Cross-Protection Elicited by Immunization with DNA Vaccines against Streptococcus pneumoniae Expressing PspA Fragments from Different Clades

Infection and Immunity ◽

10.1128/iai.70.9.5086-5090.2002 ◽

2002 ◽

Vol 70 (9) ◽

pp. 5086-5090 ◽

Cited By ~ 29

Author(s):

Eliane N. Miyaji ◽

Daniela M. Ferreira ◽

Alexandre P. Y. Lopes ◽

M. Cristina C. Brandileone ◽

Waldely O. Dias ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Dna Vaccines ◽

Protein A ◽

Sequence Divergence ◽

Surface Protein ◽

Cost Effective ◽

Cross Reactivity ◽

Cross Protection ◽

The Cross ◽

Humoral Responses

ABSTRACT Streptococcus pneumoniae is a major cause of disease, especially in developing countries, and cost-effective alternatives to the currently licensed vaccines are needed. We constructed DNA vaccines based on pneumococcal surface protein A (PspA), an antigen shown to induce protection against pneumococcal bacteremia. PspA fragments can be divided into three families, which can be subdivided into six clades, on the basis of PspA amino acid sequence divergence (S. K. Hollingshead, R. Becker, and D. E. Briles, Infect. Immun. 68:5889-5900, 2000). Since most clinical isolates belong to family 1 or family 2, PspA fragments from members of both of these families were analyzed. Vectors encoding the complete N-terminal regions of PspAs elicited significant humoral responses, and cross-reactivity was mainly restricted to the same family. DNA vaccines encoding fusions between PspA fragments from family 1 and family 2 were also constructed and were able to broaden the cross-reactivity, with induction of antibodies that showed reactions with members of both families. At least for the pneumococcal strains tested, the cross-reactivity of antibodies was not reflected in cross-protection. Animals immunized with DNA vaccines expressing the complete N-terminal regions of PspA fragments were protected only against intraperitoneal challenge with a strain expressing PspA from the same clade.

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