Pre-clinical development of BCG.HIVA(CAT), an antibiotic-free selection strain, for HIV-TB pediatric vaccine vectored by lysine auxotroph of BCG

Autor: Narcís Saubi, Maximillian Rosario, Ester Gea-Mallorquí, Joan Joseph, Tomáš Hanke, Josep M. Gatell, Alice Mbewe-Mvula
Přispěvatelé: Universitat de Barcelona
Předmět:
Immunogen
Applied Microbiology
lcsh:Medicine
CD8-Positive T-Lymphocytes
Vacunes
Pediatrics
chemistry.chemical_compound
Mice
Plasmid
Drug Discovery
Immunologia
lcsh:Science
Child
Immune Response
AIDS Vaccines
Vaccines
Multidisciplinary
Immunogenicity
Mycobacterium bovis
Immunizations
Vaccination
AIDS
Phenotype
BCG Vaccine
Medicine
Infectious diseases
Female
Public Health
Behavioral and Social Aspects of Health
Plasmids
Research Article
Biotechnology
Drugs and Devices
Drug Research and Development
Genetic Vectors
HIV prevention
Immunology
Immunization
Secondary
Sexually Transmitted Diseases
Bioengineering
Viral diseases
Biology
complex mixtures
Microbiology
Mycobacterium tuberculosis
Shuttle vector
Species Specificity
Adolescent Medicine
Escherichia coli
VIH (Virus)
Animals
Humans
HIV (Viruses)
Lysine
lcsh:R
HIV
biology.organism_classification
Virology
chemistry
HIV-1
lcsh:Q
Vaccinia
Neonatology
BCG vaccine
Zdroj: Recercat. Dipósit de la Recerca de Catalunya
instname
Dipòsit Digital de la UB
Universidad de Barcelona
PLoS ONE
PLoS ONE, Vol 7, Iss 8, p e42559 (2012)
Popis: In the past, we proposed to develop a heterologous recombinant BCG prime-recombinant modified vaccinia virus Ankara (MVA) boost dual pediatric vaccine platform against transmission of breast milk HIV-1 and Mycobacterium tuberculosis (Mtb). In this study, we assembled an E. coli-mycobacterial shuttle plasmid pJH222.HIVA(CAT) expressing HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism based on Operator-Repressor Titration (ORT) system for plasmid selection and maintenance in E. coli and lysine complementation in mycobacteria. This shuttle plasmid was electroporated into parental lysine auxotroph (safer) strain of BCG to generate vaccine BCG.HIVA(CAT). All procedures complied with Good Laboratory Practices (GLPs). We demonstrated that the episomal plasmid pJH222.HIVA(CAT) was stable in vivo over a 20-week period, and genetically and phenotypically characterized the BCG.HIVA(CAT) vaccine strain. The BCG.HIVA(CAT) vaccine in combination with MVA.HIVA induced HIV-1- and Mtb-specific interferon γ-producing T-cell responses in newborn and adult BALB/c mice. On the other hand, when adult mice were primed with BCG.HIVA(CAT) and boosted with MVA.HIVA.85A, HIV-1-specific CD8(+) T-cells producing IFN-γ, TNF-α, IL-2 and CD107a were induced. To assess the biosafety profile of BCG.HIVA(CAT)-MVA.HIVA regimen, body mass loss of newborn mice was monitored regularly throughout the vaccination experiment and no difference was observed between the vaccinated and naïve groups of animals. Thus, we demonstrated T-cell immunogenicity of a novel, safer, GLP-compatible BCG-vectored vaccine using prototype immunogen HIVA. Second generation immunogens derived from HIV-1 as well as other major pediatric pathogens can be constructed in a similar fashion to prime protective responses soon after birth.
Databáze: OpenAIRE
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