Advances and challenges in recombinant Mycobacterium bovis BCG-based HIV vaccine development: lessons learned

ABSTRACT

Introduction: Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome, tuberculosis, and malaria are responsible for most human deaths produced by infectious diseases worldwide. Vaccination against HIV requires generation of memory T cells and neutralizing antibodies, mucosal immunity, and stimulation of an innate immune responses. In this context, the use of Mycobacterium bovis bacillus Calmette–Guérin (BCG) as a live vaccine vehicle is a promising approach for T-cell induction.

Areas covered: In this review, we provide a comprehensive summary of the literature regarding immunogenicity studies in animal models performed since 2005. Furthermore, we provide expert commentary and 5-year view on how the development of potential recombinant BCG-based HIV vaccines involves careful selection of the HIV antigen, expression vectors, promoters, BCG strain, preclinical animal models, influence of preexisting immunity, and safety issues, for the rational design of recombinant BCG:HIV vaccines to prevent HIV transmission in the general population.

Expert commentary: The three critical issues to be considered when developing a rBCG:HIV vaccine are codon optimization, antigen localization, and plasmid stability in vivo. The use of integrative expression vectors are likely to improve the mycobacterial vaccine stability and immunogenicity to develop not only recombinant BCG-based vaccines expressing second generation of HIV-1 immunogens but also other major pediatric pathogens to prime protective responses shortly following birth.

KEYWORDS:

• rBCG
• HIV
• AIDS
• live-attenuated vaccines
• mycobacteria

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The manuscript was funded by the Fundación Carolina, ‘Estancias Cortas Posdoctorales’ Program, Colciencias [grant FP44842-108-2016], by Instituto de Salud Carlos III FIS PI14/00494, and the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 681137. EAVI2020.