title: A single dose of a DNA vaccine encoding apa coencapsulated with 6,6'-trehalose dimycolate in microspheres confers long-term protection against tuberculosis in Mycobacterium bovis BCG-primed mice.
abstract: Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.
authors.affiliation: Laboratory of Immunology and Immunogenetics, Evandro Chagas Clinic Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Dyego
authors.initials: D
authors.lastname: Carlétti
authors.forename: Denise
authors.initials: D
authors.lastname: Morais da Fonseca
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Gembre
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Masson
authors.forename: Lívia
authors.initials: L
authors.lastname: Weijenborg Campos
authors.forename: Luciana C C
authors.initials: LC
authors.lastname: Leite
authors.forename: Andréa
authors.initials: A
authors.lastname: Rodrigues Pires
authors.forename: Joseli
authors.initials: J
authors.lastname: Lannes-Vieira
authors.forename: Célio
authors.initials: C
authors.lastname: Lopes Silva
authors.forename: Vânia Luiza Deperon
authors.initials: VL
authors.lastname: Bonato
authors.forename: Cynthia
authors.initials: C
authors.lastname: Horn
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D058491:Bacterial Load; D003311:Cord Factors / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D003311:Cord Factors; D004337:Drug Carriers; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA