Tuhina Gupta Poster 2025

Dr Tuhina Gupta

University of Georgia, USA

Assessing protection of novel nanoparticle-based vaccine against tuberculosis

Poster Abstract

Tuberculosis (TB) is one of the deadliest infectious diseases caused by Mycobacterium tuberculosis (M. tb). M. bovis BCG, the only available vaccine is not protective in adults against the pulmonary TB. The major goal of this ongoing project is to develop a mucosal vaccine against TB. The respiratory mucosa is lined by epithelial cells particularly alveolar epithelial cells (AECs) and serve as primary targets for mucosal vaccines.

Three of the M. tb secreted proteins that are involved in infecting and trafficking within AECs are used in this novel vaccine: heparin-binding hemagglutinin adhesin (HBHA), Rv3351c (an inducer of lipid rafts), and early secretory antigenic target (ESAT6; a pore-forming protein). Recombinant fusion protein of Rv3351c and ESAT6 and native HBHA purified from BCG Pasteur are adsorbed onto two different nanoparticle (NP) types: wax or polylactic-co-glycolic acid. The NP plus protein complexes are combined in VacSIM® plus one of two well-studied M. tb vaccine adjuvants (CpG or GLA-SE). Both male and female C57Bl/6 mice age 6-8 weeks were used for the study. We compared both subcutaneous and intranasal vaccination routes and tested two boosters of the NPs one month apart to a subcutaneous BCG prime.

Preliminary results show that intranasal vaccination was more protective than the subcutaneous vaccination. The total lung bacterial load was lower than only BCG at week 8 p.i. The best vaccine combination was picked from study 1 and various amounts of the antigens were tested in study 2. Preliminary results indicate that mice vaccinated with 30 μg each of Rv3351c, ESAT6, HBHA and VacSIM had lower M. tb and proinflammatory cytokines TNFa and IL-6 in the lungs. The lungs of the NP vaccinated mice had lower number of granulomas than the BCG. An in depth scoring of the lung pathology and cytokine analysis is ongoing.