Vaccines R&D & Vaccination

Prince Sharma (56) completed his PhD at the age of 25 years and is currently Professor of Microbiology working in the areas of Reverse Vaccinology, Industrial Enzymes and Biosensors for diagnostics. He has one patent granted and two technologies transferred to industries (Cadilla, India and NEB,USA). Published 95 papers, completed 12 research projects, guided 22 PhD students.  Got Glaxo Smith Kline Vaccine Travel Award to present work on Reverse Vaccinology in ECCMID conference (2016) in Amsterdam. Defence Threat Reduction Agency, USA, sponsored him for European Biosafety Association Conference in Madrid, 2017. He is Associate Editor of Indian Journal of Microbiology and is Fellow of the Academy of Microbiological Sciences

Acinetobacter baumannii has emerged as a multi drug resistant opportunistic human pathogen causing serious nosocomial infections in immunocompromised patients. Recently, WHO has released a list of antibiotic resistant priority pathogens and mentioned A. baumannii as the critically most dangerous one. Emergence of resistant strains worldwide is a serious concern and novel approaches like vaccination could become effective in preventing A. baumannii infections.

In our lab, the pan-proteome of A. baumannii was analysed in silico to find potential vaccine candidate proteins on the basis of sub-cellular localization, number of transmembrane helices, adhesion probability, ability to bind MHCs and dissimilarity with human and mouse proteome. Out of 4589 proteins, 51 including pilus assembly proteins, competence proteins, siderophore receptor proteins, FilF, NucAb, BamA, peptidase, efflux proteins and autotransporter proteins fulfilled the criteria of good vaccine candidates. Three proteins viz. FilF, BamA and nuclease were cloned in pET28-a, expressed in E.coli BL21 (DE3) and purified. Their immunoprotective efficacies were evaluated in A. baumannii associated murine pneumonia models (intratracheal and intranasal) developed in our lab. Immunization with purified recombinant proteins evoked significant antibody titers in mouse that facilitated the reduction of bacterial load in lungs by several log cycles (2,2 by FilF immunization, 2,3 by BamA and 4,5 by nuclease 12 h and 24 h post infection respectively). Levels of pro-inflammatory TNF-α, IFN-γ, IL-1β and IL-6 cytokines were reduced and those of anti-inflammatory IL10 increased significantly. Decreased neutrophil infiltration was observed in immunized mice. Active immunization with NucAb, FilF and BamA resulted in 20, 50 and 80% survival of A. baumannii challenged mice, whereas passive immunization with NucAb and BamA resulted in 40 and 60% survival. FilF, BamA and NucAb, predicted as potential vaccine candidates by in silico analysis, showed immunoprotective efficacy and can contribute significantly in vaccine development against A. baumannii.