Recombinant BCG expressing HTI prime and recombinant ChAdOx1 boost is safe and elicits HIV-1-specific T-cell responses in BALB/c mice
Kilpeläinen, Athina (Hospital Universitari Vall d'Hebron)
Saubi, Narcis (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Guitart, Núria (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Olvera, Alex (Universitat de Vic - Universitat Central de Catalunya)
Hanke, Tomáš (Kumamoto University. International Research Center of Medical Sciences (IRCMS))
Brander, Christian. (AELIX Therapeutics)
Joseph, Joan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Data:	2019
Resum:	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 (BCG∆Lys) to generate the vaccine BCG. HTI. 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. HTI 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.
Ajuts:	Instituto de Salud Carlos III RETIC-RISRD12-0017 Instituto de Salud Carlos III FISPI14-00494 European Commission 681137
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	BCG ; HIV ; Vaccine ; Rbcg ; HTI ; T-cell
Publicat a:	Vaccines (Basel), Vol. 7 Núm. 3 (september 2019) , p. 78, ISSN 2076-393X

DOI: 10.3390/vaccines7030078
PMID: 31382453

19 p, 3.7 MB

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