Table 1.
rBCG vaccine candidates and their immune responses against various viral, parasitic, or bacterial challenges.
| Infection | BCG Strain | Gene(s)/Protein(s) expressed | Additional Antigen Details | Animal model | Type(s) of immune response noted | References | |
|---|---|---|---|---|---|---|---|
| Viral | Human immunodeficiency virus 1 (HIV-1) | Danish and Connaught | HIVconsv1&2 immunogens along with ChAdOx1.tHIVconsv5&6 (conserved HIV-1 mosaic immunogens) | Mtb19-kDa lipoprotein signal sequence | BALB/c mice | Cellular: Increased induction of IFN-γ and TNF-α, CD4+ and CD8+ CTLs. | Kilpeläinen et al., 2019 |
| Simian immunodeficiency virus (SIV) | Tokyo | SIVgag polyprotein | α antigen, extracellular secretion of fusion protein | Male cynomolgus macaques (Macaca fascicularis) | Prime-boost inoculation of rBCG-SIVgag followed by rDIsSIVgag lead to cellular responses through increased IFN-γ and immunity against SHIV challenge for one year. | Ami et al., 2005 | |
| Tokyo | SIV proteins: Gag, Env gp120 and a fusion protein of Rev., Tat and Nef (RTN) proteins | Urease-deficient BCG expressing SIV genes | Male cynomolgus macaques | Cellular: little to no plasma viremia detected, along with high levels of potent CD8+ T cells were observed, and partial or full protection from challenge. | Kato et al., 2020 | ||
| Hepatitis C virus (HCV) | Tokyo | CtEm, a multi-epitope antigen composed of HCV structural and non-structural epitopes | Signal peptide α-ss antigen derived from H37Rv Mtb, secreted CtEm protein | HLA-A2.1 transgenic mice | Th1 dominant cellular response and induction of specific anti-HCV antibodies. Protection against recombinant vaccinia virus (rVV-HCV-CNS) was observed in vivo. | Wei et al., 2008 | |
| Human metapneumovirus (hMPV) | Danish | M2-1 (participates in viral transcriptional regulation) and hMPV-P (phosphoprotein) | BALB/c mice | Th1 dominant response, induction of hMPV-specific T cells producing IFN-γ and IL-2, immunized mice were protected against disease symptoms and viral replication in the lungs. | Palavecino et al., 2014 | ||
| Respiratory syncytial virus (RSV) | Danish | RSV nucleoprotein (N) | Phase I clinical trial: 24 healthy males aged 19–44 | Serum IgG-antibodies directed against Mycobacterium and RSV N protein, induced after vaccination and neutralized RSV in vitro. Increased IFN-γ and IL-2 also observed. | Bueno et al., 2008; Abarca et al., 2020 | ||
| Rotavirus | Tokyo and Pasteur | VP6 (immunogenic intermediate-layer capsid protein) | Mtb19-kDa lipoprotein signal sequence, VP6 linked to BCG cell membrane | BALB/c mice | Up to 66% reduction in fecal viral shedding compared to controls upon rotavirus challenge. No anti-rotavirus antibody was detected, meaning antigen-specific CD4+ or CD8+ T cells are most likely mediators of protection from viral infection. | Dennehy et al., 2007 | |
| Parasitic | Plasmodium falciparum | Glaxo | CSp (circumsporozoite protein) | BALB/c mice | CS-specific antibodies and IFN-γ producing memory cells, along with increased activation of APCs for priming adaptive immunity. | Arama et al., 2012 | |
| Toxoplasma gondii | Pasteur | TgCyP (cyclophilin) | BALB/c mice | Dominant Th1 response through high levels of IFN-γ, IL-2 and IL-12, especially after oral administration. IV administration led to increased survival time and survival rate, along with high IgG specific antibody production. | Yu et al., 2013 | ||
| Trypanosoma cruzi | Pasteur | NT-TS (N and C terminal of trans-sialidase) and CZf (cruzipain enzyme) fragments | BALB/c mice | Increased level of protection and decreased level of parasitemia after challenge. Th1/Th17 responses observed through induction of IFN-γ, IL-17 and CD107 expression. | Bontempi et al., 2020 | ||
| Eimeria maxima | N/A | AMA1 (apical membrane antigen1 of E. maxima) | AMA1 present in the cellular lysate of rBCG. | One-day-old specific pathogen-free chickens | Intranasal and subcutaneous immunization lead to reduced disease symptoms. Intranasal immunization led to serum antibody, CD4+ and CD8+ T cells, IL-1β, IFN-γ, IL-15, and IL-10 induction. | Li et al., 2013 | |
| Schistosoma mansoni | Pasteur | Sm14 (fatty-acid binding protein of S. mansoni) | Complete Mycobacterium fortuitum β-lactamase protein sequence (Blam) fused to the Sm14 sequence. | BALB/c or Swiss mice | Th1 response through increased levels of IFN- γ, and 48% reduction in worm burden compared to nonvaccinated controls. | Varaldo et al., 2004 | |
| Bacterial Toxins/Antigens | Shiga toxin-producing Escherichia coli(STEC) | Tokyo | Stx2 B subunit (nontoxic shiga toxin) | BALB/c mice | Immunization led to humoral responses (protective serum IgG and mucosal IgA) and longer survival upon oral challenge. | Fujii et al., 2012 | |
| Leptospira interrogans | Pasteur | Four constructs composed of lipL32, lemA and ligANI genes (conserved, exposed Leptospira antigens) | Golden Syrian hamsters | Cellular Th1 immunity and 100% protection against leptospirosis. | Dorneles et al., 2020 | ||
| Bordetella pertussis | Moreau | S1 subunit of PT-9K/129G (genetically detoxified S1 pertussis toxin genes) | Swiss mice | Th1 dominant immune response (IFN- γ and TNF-α induction) and high levels of protection against intracerebral challenge. | Nascimento et al., 2009; Kanno et al., 2019 | ||
| Borrelia burgdorferi | Pasteur | Outer surface protein A (OspA) | Mtb19-kDa lipoprotein signal sequence, OspA expressed as a membrane-associated lipoprotein | Swiss, BALB/c, or C3H/HeJ mice | 100-1,000-fold higher protective antibody response when expressed as a membrane-associated lipoprotein when compared to cytoplasmic or secreted protein expression. | Stover et al., 1993 |