Abstract
Mycobacterium tuberculosis (Mtb) infection is one of the leading causes of death worldwide. The Modified Vaccinia Ankara (MVA) vaccine vector expressing the mycobacterial antigen 85A (MVA85A) was demonstrated to be safe, although it did not improve BCG efficacy, denoting the need to search for improved tuberculosis vaccines. In this work, we investigated the effect of IL-12 DNA -as an adjuvant- on an Ag85A DNA prime/MVA85A boost vaccination regimen. We evaluated the immune response profile elicited in mice and the protection conferred against intratracheal Mtb H37Rv challenge. We observed that the immunization scheme including DNA-A85A+DNA-IL-12/MVA85A induced a strong IFN-γ production to Ag85A in vitro, with a significant expansion of IFN-γ+CD4+ and IFN-γ+CD8+ anti-Ag85A lymphocytes. Furthermore, we also detected a significant increase in the proportion of specific CD8+CD107+ T cells against Ag85A. Additionally, inclusion of IL-12 DNA in the DNA-A85A/MVA85A vaccine scheme induced a marked augment in anti-Ag85A IgG levels. Interestingly, after 30 days of infection with Mtb H37Rv, DNA-A85A+DNA-IL-12/MVA85A vaccinated mice displayed a significant reduction in lung bacterial burden. Together, our findings suggest that IL-12 DNA might be useful as a molecular adjuvant in an Ag85A DNA/MVA prime-boost vaccine against Mtb infection.
Highlights
Tuberculosis (TB) continues to be one of the main global health problems
Our findings indicate that IL-12 DNA might be used to increase the host immune response generated by MVA expressing the mycobacterial antigen 85A (MVA85A) against Mycobacterium tuberculosis (Mtb) infection
After 14 days of the last priming dose, mice were i.p. boosted with 107 plaque-forming units (PFU)/animal of MVA85A
Summary
Tuberculosis (TB) continues to be one of the main global health problems. Despite the excellent progress of the Directly Observed Treatment (DOT) strategy, and affordable and effective anti-TB treatments, the World Health Organization estimated 1.45 million deaths due to Mycobacterium tuberculosis (Mtb) infection in 2018 (World Health Organization, 2019). TB has always been correlated with poverty, especially in low- and middle-income countries. IL-12 DNA in Ag85A Immunogenicity the incidence of TB has increased even in industrialized countries, mainly in vulnerable groups. The strategies for TB control have been hampered by the Human Immunodeficiency Virus (HIV) co-infection and the emergence of drug-resistant Mtb strains. Developing a vaccine capable of preventing Mtb infection would contribute to controlling the TB epidemic
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