Mrs Sadaf Sulman
University of the Punjab, Pakistan
Balance between Protection and Pathogenic Response to Aerosol Challenge with Mycobacterium tuberculosis (Mtb) in Mice Vaccinated with TriFu64, a Fusion Consisting of Three Mtb Antigens
Poster Abstract
Tuberculosis vaccines capable of reducing disease worldwide have proven difficult to develop. BCG is effective in limiting childhood disease, but adult TB is still a major public health issue. Development of new vaccines requires identification of antigens that are both spatially and temporally available throughout infection, and immune responses to which reduce bacterial burden without increasing pathologic outcomes. Subunit vaccines containing antigen require adjuvants to drive appropriate long-lived responses. We generated a triple-antigen fusion containing the virulence- associated EsxN (Rv1793), the PPE42 (Rv2608), and the latency associated Rv2628 to investigate the balance between bacterial reduction and weight loss in an animal model of aerosol infection. We found that in both a low pattern recognition receptor (PRR) engaging adjuvant and a high PRR- engaging adjuvant (MPL/TDM/DDA) the triple-antigen fusion could reduce the bacterial burden, but also induced weight loss in the mice upon aerosol infection. The weight loss was associated with an imbalance between TNFα and IL-17 transcription in the lung upon challenge. These data indicate the need to assess both protective and pathogenic responses when investigating subunit vaccine activity.
Biography
I completed my BS honors (2010) and MS (2012) in Microbiology and Molecular Genetics (MMG) from the Institute of Microbiology and Molecular Genetics, University of the Punjab (PU), Lahore.
In 2014, I resumed my career with short term research fellow in School of Biological Sciences (SBS), PU under the project US-PAK project: “Rapid and Reliable Detection of Infection and Drug Resistance of Tuberculosis through Multiplex Analysis” that was my first-time experience with Mtb and TB research. My interest and hard work led me to get a PhD offer by the Principal Investigator Prof. Waheed Akhtar who was also my PhD supervisor. In Oct. 2014, I started my PhD, the project was focussed towards the development of Mtb based multi-epitope fusion proteins for serodiagnostic purpose. During the lab work I have also worked as a Research Fellow in another TB-based project “Development and commercialization of blood-based tuberculosis diagnostic test”. In 2017, I secured Commonwealth Split-site Scholarship for University of Leicester, UK. There I learned T-cell Immunology under the supervision of Prof. Andrea Cooper. This joint collaboration allowed me to study my novel fusion protein (TriFu64) as a vaccine in mice model. This work has been published in Vaccines (MDPI) journal. My PhD thesis was entitled as “Assessment of T-cell responses to novel fusion proteins in Mycobacterium tuberculosis-infected and vaccinated mice”. After returning back to my home country I tested TriFu64 fusion protein as a serodiagnostic tool using human plasma samples of local population with promising results followed by another publication in PlosOne. I have recently finished my PhD and defended my thesis in February 2021. I'm looking for post doc positions in the UK focussed on TB research and vaccine development.
