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Open AccessArticle

Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c Mice

1
Catalan Center for HIV Vaccine Research and Development, AIDS Research Unit, Infectious Diseases Department, Hospital Clínic/IDIBAPS, 08036 Barcelona, Catalonia, Spain
2
Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, 08035 Barcelona, Catalonia, Spain
3
Irsicaixa AIDS Research Institute, 08916 Badalona, Catalonia, Spain
4
Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), 08500 Vic, Barcelona, Spain
5
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
6
International Research Center of Medical Sciences (IRCMS), Kumamoto University, Kumamoto 860-0811, Japan
7
ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Catalonia, Spain
8
AELIX Therapeutics, 08028 Barcelona, Catalonia, Spain
*
Author to whom correspondence should be addressed.
Vaccines 2019, 7(3), 78; https://doi.org/10.3390/vaccines7030078
Received: 10 May 2019 / Revised: 11 July 2019 / Accepted: 24 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Advances in DNA Vaccines)
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. View Full-Text
Keywords: BCG; HIV; vaccine; rBCG; HTI; T-cell BCG; HIV; vaccine; rBCG; HTI; T-cell
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Kilpeläinen, A.; Saubi, N.; Guitart, N.; Olvera, A.; Hanke, T.; Brander, C.; Joseph, J. 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, 7, 78.

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