Prime-boost vaccination based on DNA and protein-loaded microspheres for tuberculosis prevention.
We evaluated the use of a vaccine formulation based on a mixture of two different PLGA microspheres, composed by faster and slower release profiles, containing DNA encoding hsp65 and the recombinant hsp65 protein, respectively, aiming to DNA priming and protein boost after a single dose vaccination. The combination of PLGA50:50 microspheres containing DNA-hsp65 and trehalose dimycolate (TDM) with PLGA75:25 microspheres containing recombinant hsp65 (prime-boost Me) was able to induce high levels of anti-hsp65 specific antibodies. The serum levels of these specific antibodies remained high during 90 days after vaccination, whereas the DNA Me formulation based only in DNA-hsp65 plus TDM-loaded microspheres was not able to sustain the high antibody levels during the same period. Production of IFN-gamma was significant in animals vaccinated with both formulations, while the prime-boost Me vaccinated mice sustained higher levels of this cytokine during all the evaluation period. Thus, prime-boost strategy by using biodegradable microspheres seems to be a promising strategy to stimulate long-lasting immune response.
Ruberti
Maristela
M
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo. Av. Bandeirantes 3.900, Ribeirão Preto, São Paulo 14049-900, Brazil.
De Melo
Lima Karla
LK
Dos Santos
Sandra Aparecida
SA
Brandao
Izaira Tincani
IT
Soares
Edson Garcia
EG
Silva
Célio Lopes
CL
Júnior
José Maciel Rodrigues
JM
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D018834:Chaperonin 60; D018833:Chaperonins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000097:blood; D007117:Immunization, Secondary / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D019344:Lactic Acid / Q000737:chemistry*; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D011108:Polymers; D011994:Recombinant Proteins; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma; D018833:Chaperonins