Protection against Mycobacterium tuberculosis challenge in mice by DNA vaccine Ag85A-ESAT-6-IL-21 priming and BCG boosting.

Tuberculosis (TB) is one of most important chronic infectious diseases caused by Mycobacterium tuberculosis and remains a major global health problem. In the study, we developed the DNA vaccine encoding fusion protein of antigen 85 A and 6 kDa early secretory antigen target of M. tuberculosis as well as the cytokine IL-21 to investigate its immune protective efficacy against M. tuberculosis challenge in mice after the DNA vaccine priming and Bacille Calmette-Guérin (BCG) boosting. Compared with the different control groups, the intranasal DNA vaccine priming twice and BCG boosting once markedly increased the cytotoxicities of natural killer cells and splenocytes and enhanced the interferon-γ level in the splenocyte supernatant as well as sIgA level in bronchoalveolar lavage in the vaccinated mice. Importantly, this heterologous prime-boost strategy significantly decreased the bacterial load in the mouse lungs in contrast to that of intranasal or subcutaneous BCG immunization alone. These findings provide further approaches for mucosal-targeted prime-boost vaccination to fight against TB.

Dou J ，Wang Y ，Yu F ，Yang H ，Wang J ，He X ，Xu W ，Chen J ，Hu K ... -  《-》

Priming but not boosting with plasmid DNA encoding mycolyl-transferase Ag85A from Mycobacterium tuberculosis increases the survival time of Mycobacterium bovis BCG vaccinated mice against low dose intravenous challenge with M. tuberculosis H37Rv.

Romano M ，D'Souza S ，Adnet PY ，Laali R ，Jurion F ，Palfliet K ，Huygen K ... -  《VACCINE》

Investigation of immunogenic effect of the BCG priming and Ag85A- GM-CSF boosting in Balb/c mice model.

Dou J ，Tang Q ，Yu F ，Yang H ，Zhao F ，Xu W ，Wang J ，Hu W ，Hu K ，Liou C ，Feng He X ，Wang Y ... -  《-》

Mucosal prime-boost vaccination for tuberculosis based on TLR triggering OprI lipoprotein from Pseudomonas aeruginosa fused to mycolyl-transferase Ag85A.

Gartner T ，Baeten M ，Otieno S ，Revets H ，De Baetselier P ，Huygen K ... -  《IMMUNOLOGY LETTERS》

Subunit vaccine candidate AMM down-regulated the regulatory T cells and enhanced the protective immunity of BCG on a suitable schedule.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) priming and subunit vaccine boosting strategies are urgently needed to improve the protective efficacy of BCG in adult population. However, the schedule of subunit vaccine boosting is not well investigated, especially the optimal immune responses and vaccine immunization schedules are still not clear. We have constructed a novel subunit vaccine candidate consisting of fusion protein Ag85B-Mpt64 (190-198)-Mtb8.4 (AMM) in a complex adjuvant composed of dimo-thylidioctyl ammonium bromide (DDA) and BCG polysaccharide nucleic acid (BCG-PSN). In this study, we compared the effect of different boosting schedules of the subunit vaccine in the prime-boost strategies. C57BL/6 mice were primed with BCG first and then boosted with the AMM vaccine once at 10th week, twice at 8th, 10th week, or thrice at 6th, 8th, 10th week, respectively. The immune responses were evaluated at the 14th and 20th weeks, respectively. Twelve weeks after the last immunization, the mice were challenged with virulent Mycobacterium tuberculosis strain H37Rv, and the protective effect was evaluated. The results showed that BCG priming and the AMM vaccine boosting twice induced the strongest antigen-specific IFN-γ and IL-2 production, down-regulated CD4+ CD25+ FoxP3+ regulatory T cells (Tregs) and had the best protective effect among all groups, while boosting thrice induced the strongest IL-4 production and did not improve BCG-primed protection significantly. Boosting BCG with the AMM vaccine twice instead of once or thrice induced strong Th1-type immunity and down-regulated Tregs significantly, which correlated with the best protection against M. tuberculosis infection in mice.

Luo Y ，Jiang W ，Da Z ，Wang B ，Hu L ，Zhang Y ，An R ，Yu H ，Sun H ，Tang K ，Tang Z ，Wang Y ，Jing T ，Zhu B ... -  《-》