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

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.

Vaccines for COVID-19: perspectives from nucleic acid vaccines to BCG as delivery vector system

“…It is possible to construct rBCG strains expressing different levels of viral, bacterial or parasitic pathogens antigens, resulting in the activation of cellular and/or humoral immune response depending on the vector and antigen [ 111 ]. BCG vaccine expressing HIV immunogens demonstrated its efficiency in activating the production of cytokines and T cell responses in mice, showing a strong potential as an integrative vaccine against HIV-1/TB or as a priming associated with other virus vector boost vaccines [ [112] , [113] , [114] , [115] ]. Different rBCG strains expressing specific antigens have induced protection against the challenge with the respective pathogen, including Borrelia burgdorferi , Streptococcus pneumoniae , Leishmania major and Plasmodium falciparum [ [116] , [117] , [118] , [119] , [120] ].…”

Vaccine strategies for the Mtb/HIV copandemic

“…Development of a combined vaccine to combat both TB and HIV is an ardent but tenable ambition. Numerous studies have focused on the induction of specific humoral and cellular immune responses against HIV-1 following recombinant BCG (rBCG) expressing HIV-1 antigens [8][9][10][11][12][13] . rBCG is an excellent vaccine vehicle that elicits the prerequisites of a successful HIV vaccine; neutralizing antibodies, stimulation of CD4 + and CD8 + T cells and a long-lasting innate and adaptive immune response 10,14,15 .…”

BCG as a Vector for Novel Recombinant Vaccines against Infectious Diseases and Cancers

“…and boosted with MVA-Gag than in those receiving the MVA-Gag boost alone [12]. rBCG expressing the HIVACAT T-cell immunogen (HTI), when delivered in combination with chimpanzee adenovirus (ChAd)Ox1.HTI in mice, induced HIV-1-specific T-cell responses [15]. Furthermore, priming with rBCG doubled the magnitude of the T-cell response in comparison with ChAdOx1.HTI alone while maintaining its breadth [15].…”