Recombinant BCG expressing HTI prime and recombinant ChAdOx1 boost is safe and elicits HIV-1-specific T-cell responses in BALB/c mice

dc.contributor
[Kilpeläinen A, Saubi N, Joseph J] Catalan Center for HIV Vaccine Research and Development, AIDS Research Unit, Servei de Malalties Infeccioses, Hospital Clínic/Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Hospital Universitari Vall d’Hebron, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Guitart N] Catalan Center for HIV Vaccine Research and Development, AIDS Research Unit, Servei de Malalties Infeccioses, Hospital Clínic/Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. [Olvera A] Irsicaixa AIDS Research Institute, Badalona, Spain. Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Barcelona, Spain. [Hanke T] Nueld Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK. International Research Center of Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan. [Brander C] ] Irsicaixa AIDS Research Institute, Badalona, Spain. Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Barcelona, Spain. ICREA, Barcelona, Spain. AELIX Therapeutics, Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Kilpeläinen, Athina
dc.contributor.author
Saubí Roca, Narcís
dc.contributor.author
Guitart, Núria
dc.contributor.author
Olvera, Alex
dc.contributor.author
Hanke, Tomáš
dc.contributor.author
Brander, Christian
dc.contributor.author
Joseph Munné, Joan
dc.date.accessioned
2025-10-24T08:55:53Z
dc.date.available
2025-10-24T08:55:53Z
dc.date.issued
2020-02-24T10:59:21Z
dc.date.issued
2020-02-24T10:59:21Z
dc.date.issued
2019-08-02
dc.identifier
Kilpeläinen A, Saubi N, Guitart N, Olvera A, Hanke T, Brander C, et al. Recombinant BCG expressing HTI prime and recombinant ChAdOx1 boost is safe and elicits HIV-1-specific T-cell responses in BALB/c mice. Vaccines. 2019 Aug 2;7(3):78.
dc.identifier
2076-393X
dc.identifier
https://hdl.handle.net/11351/4671
dc.identifier
10.3390/vaccines7030078
dc.identifier
31382453
dc.identifier
000487982000034
dc.identifier.uri
http://hdl.handle.net/11351/4671
dc.description.abstract
BCG; HIV; Vaccine
dc.description.abstract
BCG; VIH; Vacuna
dc.description.abstract
BCG; VIH; Vacuna
dc.description.abstract
Despite the availability of anti-retroviral therapy, HIV-1 infection remains a massive burden on healthcare systems. Bacillus Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis, confers protection against meningitis and miliary tuberculosis in infants. Recombinant BCG has been used as a vaccine vehicle to express both HIV-1 and Simian Immunodeficiemcy Virus (SIV) immunogens. In this study, we constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HTI.int, expressing the HIVACAT T-cell immunogen (HTI). The plasmid was transformed into a lysine auxotrophic Mycobacterium bovis BCG strain (BCGΔLys) to generate the vaccine BCG.HTI2auxo.int. The DNA sequence coding for the HTI immunogen and HTI protein expression were confirmed, and working vaccine stocks were genetically and phenotypically characterized. We demonstrated that the vaccine was stable in vitro for 35 bacterial generations, and that when delivered in combination with chimpanzee adenovirus (ChAd)Ox1.HTI in adult BALB/c mice, it was well tolerated and induced HIV-1-specific T-cell responses. Specifically, priming with BCG.HTI2auxo.int doubled the magnitude of the T-cell response in comparison with ChAdOx1.HTI alone while maintaining its breadth. The use of integrative expression vectors and novel HIV-1 immunogens can aid in improving mycobacterial vaccine stability as well as specific immunogenicity. This vaccine candidate may be a useful tool in the development of an effective vaccine platform for priming protective responses against HIV-1/TB and other prevalent pediatric pathogens.
dc.description.abstract
This research was funded by the European Union's Horizon 2020 research and innovation program under grant agreement No. 681137 and supported by Instituto de Salud Carlos III FIS PI14/00494. EAVI2020. In addition, it has been supported by the ISCIII, RETIC-RIS RD12/0017, and the HIVACAT Research Program.
dc.format
application/pdf
dc.language
eng
dc.publisher
MDPI
dc.relation
Vaccines;7(3)
dc.relation
https://www.mdpi.com/2076-393X/7/3/78
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.source
Scientia
dc.subject
Mycobacterium tuberculosis
dc.subject
Vacunes antivíriques
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Sida - Vacunació
dc.subject
CHEMICALS AND DRUGS::Complex Mixtures::Biological Products::Vaccines::Viral Vaccines::AIDS Vaccines
dc.subject
PHENOMENA AND PROCESSES::Immune System Phenomena::Immune System Phenomena::Immunity::Adaptive Immunity::Immunity, Active::Immune System Phenomena::Immunity::Adaptive Immunity::Immune System Phenomena::Immunogenicity, Vaccine
dc.subject
ORGANISMS::Bacteria::Gram-Positive Bacteria::Actinobacteria::Actinomycetales::Mycobacteriaceae::Mycobacterium::Mycobacterium bovis
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COMPUESTOS QUÍMICOS Y DROGAS::mezclas complejas::productos biológicos::vacunas::vacunas víricas::vacunas para SIDA
dc.subject
FENÓMENOS Y PROCESOS::fenómenos del sistema inmunitario::fenómenos del sistema inmunitario::inmunidad::inmunidad adaptativa::fenómenos del sistema inmunitario::inmunidad::inmunidad adaptativa::fenómenos del sistema inmunitario::inmunogenicidad vacunal
dc.subject
ORGANISMOS::Bacteria::bacterias grampositivas::Actinobacteria::Actinomycetales::Mycobacteriaceae::Mycobacterium::Mycobacterium bovis
dc.title
Recombinant BCG expressing HTI prime and recombinant ChAdOx1 boost is safe and elicits HIV-1-specific T-cell responses in BALB/c mice
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion


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