Vaccine Description Results Reference
Fusion proteins from MTB antigens as vaccines
Ag85B-TB10.4/IC31 Ag85B-TB10.4 delivered in IC31 adjuvant Vaccination resulted in high numbers of polyfunctional CD4 T cells co-expressing IL-2, IFN-gamma and TNF-alpha. This correlated with protection against virulent challenge in the TB mouse model [131]
Mtb72F a 72-kDa polyprotein genetically linked in tandem in the linear order Mtb32(C)-Mtb39-Mtb32(N) Immunization of guinea pigs resulted in more than 1 year survival after virulent challenge when compared to BCG. [132]
Mtb72F + AS02 Mtb72F in the GSK proprietary adjuvant system AS02 Vaccine was immunogenic and caused no adverse reactions in cynomolgus monkeys. Superior protection afforded with BCG prime- Mtb72F in AS02A boost, compared to that with BCG alone. Monkeys also survived longer and showed reversal of disease progression [133]
ID83 fusion protein (ID83), which contains the three Mtb proteins Rv1813, Rv3620 and Rv2608 ID83 + synthetic TLR4 or TLR9 agonists generated a T helper-1 immune response and protected mice against Mtb challenge with regardless of route. [134]
Viral-vectored vaccines
MVA85A/ Aeras-485 Attenuated vaccinia Ankara virus expressing Ag85A Induced high levels of antigen-specific IFN-gamma-secreting T cells when used alone in BCG-naive healthy volunteers.
In BCG vaccinated volunteers, substantially higher levels of antigen-specific IFN-gamma-secreting T cells were induced, and at 24 weeks after vaccination these levels were 5-30 times greater than in those receiving a single BCG dose.
Crucell Ad35/ Aeras 402 Adenovirus 35 expressing 3 antigens Confers protection against MTB after intranasal or IM immunization in the mouse model. Histological evaluation revealed differences in immune response between two mouse strains that were elucidated by epitope mapping analysis. a dominant CD8 T-cell response was detected in BALB/c (H-2(d)) mice whereas a more balanced CD4/CD8 T-cell responses were observed in C57BL/6 (H-2(b)) mice [136]
AdAg85A Adenovirus 5 expressing only Ag85A A single intranasal but not IM immunization was able to induce potent protection from MTB challenge in a mouse model
Also used to boost mice primed with SC BCG, showing enhanced protection that was correlated with the numbers of IFN-gamma CD4+ and CD8+ in airway lumen
Table 2: Summary of new subunit vaccine candidates against TB (modified from [49,130]).