Abstract
Adults are the leading population affected by tuberculosis (TB) epidemic and death. Developing an effective vaccine against adult TB is urgently needed. Mycobacterium bovis Bacillus Calmette-Guerin (BCG) prime-heterologous boost strategy has been explored extensively to protect adults against primary TB infection, but the majority of experimental regimens have not improved the protection primed by the BCG vaccine. The reason attributed to the failure remains unknown. In this study, CTT3H-based vaccines, namely DMT adjuvanted CTT3H subunit or DNA vaccine (pCTT3H-DMT), and recombinant adenovirus rAdCTT3H were constructed. Protective efficacy and immunogenicity of BCG prime-CTT3H based boosters were compared in C57BL/c mice models of primary or late persistent TB infection. Similar protective efficacy against early intranasal infection was provided by different CTT3H-based vaccines alone in vaccinated mice, and their protection was inferior to that of the BCG vaccine. In addition, CTT3H-based heterologous boosters did not enhance the protection conferred by the BCG vaccine against primary infection. However, all of these three boosters provided stronger protection against late persistent TB infection than BCG alone, regardless of vaccine types. Although BCG prime-boosters elicited Th1-biased responses to the antigen CTT3H, the number of CTT3H-sepcific IFN-γ-expressing TEM (CD62LloCD44hi) and IL-2-expressing TCM (CD62LhiCD44hi) cells in the spleen was not improved before exposure to Mycobacterium tuberculosis infection. In contrast, IFN-γ+ TEM and IL-2+ TCM cells in spleens, especially in lungs were significantly increased in BCG prime-boosters after exposure vaccination. Our results indicate that BCG prime-boost strategy might be a promising measure for the prevention against late persistent TB infection by induction of IFN-γ+ TEM and IL-2+ TCM cells in the lung, which can be used as alternative biomarkers for guiding the clinical practice and future development of TB vaccine for adults.
Highlights
Despite significant progress in the pipeline for new diagnostics, drugs, and vaccine candidates, tuberculosis (TB) remains one of the deadliest killers among infectious diseases [1]
To evaluate the effect of vaccine types on the protection, the protective efficacy against primary M. tuberculosis infection between DMT adjuvanted CTT3H subunit protein vaccine, DNA vaccine pCTT3H in adjuvant of DMT, and recombinant adenovirus rAdCTT3H vaccine were firstly compared in different vaccinated mice
Our results demonstrated that similar protective efficacy was provided by CTT3H-DMT, pCTT3H-DMT, and rAdCTT3H alone in vaccinated mice against primary infection but that protection was inferior to that of the Bacillus Calmette-Guerin (BCG) vaccine
Summary
Despite significant progress in the pipeline for new diagnostics, drugs, and vaccine candidates, tuberculosis (TB) remains one of the deadliest killers among infectious diseases [1]. As the only licensed vaccine for TB, Mycobacterium bovis Bacillus CalmetteGuerin (BCG) is recommended to vaccinate infants worldwide and can provide effective protection against several serious forms of TB in children even though its protection wanes with time and only lasts 10–15 years [2]. As estimated by WHO in 2017, there were ∼ 10 million new TB cases, and 90% occurred in adults with only 10% in children [1]. One-third of the world population is estimated to have latent TB infection (LTBI), of which 5–10% would progress to active TB during their lifetime [3]. There is an urgent need to develop an effective vaccine against adult TB
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call