title: Prime-boost BCG vaccination with DNA vaccines based in β-defensin-2 and mycobacterial antigens ESAT6 or Ag85B improve protection in a tuberculosis experimental model.
abstract: The World Health Organization (WHO) has estimated that there are about 8 million new cases annually of active Tuberculosis (TB). Despite its irregular effectiveness (0-89%), the Bacillus Calmette-Guérin) BCG is the only vaccine available worldwide for prevention of TB; thus, the design is important of novel and more efficient vaccination strategies. Considering that β-defensin-2 is an antimicrobial peptide that induces dendritic cell maturation through the TLR-4 receptor and that both ESAT-6 and Ag85B are immunodominant mycobacterial antigens and efficient activators of the protective immune response, we constructed two DNA vaccines by the fusion of the gene encoding β-defensin-2 and antigens ESAT6 (pDE) and 85B (pDA). After confirming efficient local antigen expression that induced high and stable Interferon gamma (IFN-γ) production in intramuscular (i.m.) vaccinated Balb/c mice, groups of mice were vaccinated with DNA vaccines in a prime-boost regimen with BCG and with BCG alone, and 2 months later were challenged with the mild virulence reference strain H37Rv and the highly virulent clinical isolate LAM 5186. The level of protection was evaluated by survival, lung bacilli burdens, and extension of tissue damage (pneumonia). Vaccination with both DNA vaccines showed similar protection to that of BCG. After the challenge with the highly virulent Mycobacterium tuberculosis strain, animals that were prime-boosted with BCG and then boosted with both DNA vaccines showed significant higher survival and less tissue damage than mice vaccinated only with BCG. These results suggest that improvement of BCG vaccination, such as the prime-boost DNA vaccine, represents a more efficient vaccination scheme against TB.
authors.affiliation: Medical Research Unit-Zacatecas, Mexican Institute of Social Security IMSS, Zacatecas, Mexico.
authors.forename: Alberto R
authors.initials: AR
authors.lastname: Cervantes-Villagrana
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
authors.forename: Arya
authors.initials: A
authors.lastname: Biragyn
authors.forename: Julio
authors.initials: J
authors.lastname: Castañeda-Delgado
authors.forename: Monica
authors.initials: M
authors.lastname: Bodogai
authors.forename: Margarita
authors.initials: M
authors.lastname: Martínez-Fierro
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sada
authors.forename: Valentin
authors.initials: V
authors.lastname: Trujillo
authors.forename: Antonio
authors.initials: A
authors.lastname: Enciso-Moreno
authors.forename: Bruno
authors.initials: B
authors.lastname: Rivas-Santiago
mesh_terms: D000217:Acyltransferases / Q000235:genetics; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics; D004195:Disease Models, Animal; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C106641:DEFB4A protein, human; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D023083:beta-Defensins; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis