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....

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Veröffentlicht in:Journal of drug targeting 2004-05, Vol.12 (4), p.195-203
Hauptverfasser: Ruberti, Maristela, Lima, Karla de Melo, dos Santos, Sandra Aparecida, Brandao, Izaira Tincani, Soares, Edson Garcia, Silva, Célio Lopes, Rodrigues Júnior, José Maciel
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container_end_page 203
container_issue 4
container_start_page 195
container_title Journal of drug targeting
container_volume 12
creator Ruberti, Maristela
Lima, Karla de Melo
dos Santos, Sandra Aparecida
Brandao, Izaira Tincani
Soares, Edson Garcia
Silva, Célio Lopes
Rodrigues Júnior, José Maciel
description 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- 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.
doi_str_mv 10.1080/10611860410001723126
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dosage</topic><topic>Chaperonins - genetics</topic><topic>Chaperonins - immunology</topic><topic>Cytokines - blood</topic><topic>DNA vaccines</topic><topic>Hsp65</topic><topic>Immunization, Secondary - methods</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Lactic Acid - chemistry</topic><topic>Lung - pathology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microspheres</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - pathogenicity</topic><topic>Particle Size</topic><topic>PLGA microspheres</topic><topic>Polyglycolic Acid - chemistry</topic><topic>Polymers - chemistry</topic><topic>Prime boost</topic><topic>Recombinant Proteins - administration &amp; dosage</topic><topic>Recombinant Proteins - immunology</topic><topic>Spleen - metabolism</topic><topic>Time Factors</topic><topic>Tuberculosis</topic><topic>Tuberculosis, Pulmonary - immunology</topic><topic>Tuberculosis, Pulmonary - microbiology</topic><topic>Tuberculosis, Pulmonary - prevention &amp; 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source MEDLINE; Taylor & Francis Medical Library - CRKN; Taylor & Francis Journals Complete
subjects Animals
Antibodies, Bacterial - blood
Bacterial Proteins - administration & dosage
Bacterial Proteins - genetics
Bacterial Proteins - immunology
Chaperonin 60
Chaperonins - administration & dosage
Chaperonins - genetics
Chaperonins - immunology
Cytokines - blood
DNA vaccines
Hsp65
Immunization, Secondary - methods
Interferon-gamma - biosynthesis
Lactic Acid - chemistry
Lung - pathology
Mice
Mice, Inbred BALB C
Microspheres
Mycobacterium tuberculosis
Mycobacterium tuberculosis - pathogenicity
Particle Size
PLGA microspheres
Polyglycolic Acid - chemistry
Polymers - chemistry
Prime boost
Recombinant Proteins - administration & dosage
Recombinant Proteins - immunology
Spleen - metabolism
Time Factors
Tuberculosis
Tuberculosis, Pulmonary - immunology
Tuberculosis, Pulmonary - microbiology
Tuberculosis, Pulmonary - prevention & control
Vaccines, DNA - administration & dosage
title Prime-boost Vaccination based on DNA and Protein-loaded Microspheres for Tuberculosis Prevention
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