title: A subunit vaccine based on biodegradable microspheres carrying rHsp65 protein and KLK protects BALB/c mice against tuberculosis infection.
abstract: Of the hundreds of new tuberculosis (TB) vaccine candidates, some have therapeutic value in addition to their prophylactic properties. This is the case for the DNA vaccine encoding heat-shock protein 65 (DNAhsp65) from Mycobacterium leprae. However, there are concerns about the use of DNA vaccines in certain populations such as newborns and pregnant women. Thus, the optimization of vaccination strategies that circumvent this limitation is a priority. This study evaluated the efficacy of a single dose subunit vaccine based on recombinant Hsp65 protein against infection with M. tuberculosis H37Rv. The Hsp65 protein in this study was either associated or not with immunostimulants, and was encapsulated in biodegradable PLGA microspheres. Our results demonstrate that the protein was entrapped in microspheres of adequate diameter to be engulfed by phagocytes. Mice vaccinated with a single dose of Hsp65-microspheres or Hsp65+CpG-microspheres developed both humoral and cellular-specific immune responses. However, they did not protect mice against challenge with M. tuberculosis. By contrast, Hsp65+KLK-microspheres induced specific immune responses that reduced bacilli loads and minimized lung parenchyma damage. These data suggest that a subunit vaccine based on recombinant protein Hsp65 is feasible.
authors.affiliation: The Centre for Tuberculosis Research, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Sandra Aparecida
authors.initials: SA
authors.lastname: dos Santos
authors.forename: Carlos Rodrigo
authors.initials: CR
authors.lastname: Zárate-Bladés
authors.forename: Fábio Cícero
authors.initials: FC
authors.lastname: de Sá Galetti
authors.forename: Izaíra Tincani
authors.initials: IT
authors.lastname: Brandão
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Masson
authors.forename: Edson Garcia
authors.initials: EG
authors.lastname: Soares
authors.forename: Ana Paula Ulian
authors.initials: AP
authors.lastname: Araújo
authors.forename: Celio Lopes
authors.initials: CL
authors.lastname: Silva
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018834:Chaperonin 60 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D019344:Lactic Acid / Q000008:administration & dosage / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D018834:Chaperonin 60; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C074119:heat-shock protein 65, Mycobacterium; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid