Table 2.
A selection of peptide-based subunit vaccines under pre-clinical investigation.
| Protein * (Rv Code) Position | Peptide Sequence | Formulation | Immunization | Efficacy | Ref. |
|---|---|---|---|---|---|
| TB10.4 (Rv0288) 4–11 and Ag85B (Rv1886c) 280–294 | IMYNYPAM and FQDAYNAAGGHNAVF |
Self-assembling peptide nanofibres with KFE8 (FKFEFKFE) + Pam2Cys adjuvant | Intranasal boosting of BCG-primed C57BL6 mice | 8-fold expansion in multifunctional CD8+ T cell populations in the lungs and 1.3 log10 CFU reduction in lung bacterial burden. | [79] |
| Ag85B (Rv1886c) 96–111 and Ag85B (Rv1886c) 241–256 | QDAYNAAGGHNAVFN and PAFEWYYQSGLSIVMP | Covalently conjugated to RVG peptide | C57BL/6 mice, s.c. or intranasal immunization | Enhances antigen presentation and in vivo immunogenicity. | [85] |
| ESAT6 (Rv3875) 51–70 | YQGVQQKWDATATELNNALQ | DDA/MPL-A/IL2 emulsion | B6CBAF1 mice, s.c. at the back 3x | Protective immunity against Mtb (around 1 log reduction in bacterial numbers). | [86] |
| ESAT6 (Rv3875) (1–15) | MTEQQWNFAGIEAAA | CAF01 | CB6F1 mice, s.c. at the base of the tail | Vaccine-promoted polyfunctional T cell response. | [87] |
| acr (Rv2031c) 91–110 | SEFAYGSFVRTVSLPVGADE | Covalently attached to Pam2Cys | BALB/c mice or Duncan-Hartley guinea pigs, i.p. or s.c. 2x | Significant protection against Mtb infection in guinea pigs and mice. | [76] |
| (Rv1733c) 57–84 | IPFAAAAGTAVQDSRSHVYAHQAQTRHP | Synthetic long peptide (SLP) with CpG ODN1826 adjuvant | HLA-DR3 transgenic mice injected 3x s.c. | Induces protection against live Mtb challenge and has therapeutic effect when used as a boost a prior BCG vaccination. | [74] |
| Ag85B (Rv1886c) 239–247 and IniB (Rv0341) 33–45 and PPE68 (Rv3873) 127–136 | KLVANNTRL and GLIDIAPHQISSV and FFGINTIPIA | Branched chain palmitoyl-peptide conjugate on Tuftsin (TKPKG) carrier | BALB/cmice injected 3-times s.c. | Significantly lower number of bacteria in the spleen after i.p. challenge with Mtb. | [80] |
| hsp65 (Rv0440) 3–13 and Ag85B (Rv1886c) 56–64 and 19 kDa (Rv3763) 51–61 and hsp16 (Rv2031c) 31–50 and (Rv1733c) 63–77 | KTIAYDEEARR and PSMGRDIKV and KVVIDGKDQNV and LRPTFDTRLMRLEDEMKEGR and AGTAVQDSRSHVYAH |
Recompinant polyepitope with CpG ODN1826 adjuvant | HLA-DR3 transgenic mice injected 3-times s.c. | Induces significant numbers (12.7%) of IFN- +/IL-2+/TNF+ CD4+ T-cells and reduce CFU in lungs of Mtb infected HLA-DR3 mice. |
[88] |
| MPT64 (Rv1980c) 190–198 And (Rv0476) 1–6 |
FAVTNDGVI and f-MLVLLV |
Peptide-pulsed BMDCs | C57BL/6 mice injected iv with 106 peptide-pulsed BMDC | Elicited an expansion of peptide-specific CD8+ T-cells in the spleen and the lung, and a significant protection against an intratracheal challenge with Mtb. | [89] |
* Protein names are used in the format as they were found in the cited reference. RVG: a 29 amino acid peptide (YTIWMPENPRPGTPCDIFTNSRGKRASNG) derived from Rabies Virus Glycoprotein that binds to the α-7 subunit of nicotinic acetylcholine receptors (AchR) of neuronal cells. CpG ODN1826: a synthetic immunostimulatory oligonucleotide that contains unmethylated CpG dinucleotides (a known TLR9 agonist).