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Salmonella  is responsible for causing enteric fever, septicemia, and gastroenteritis in humans. Due to high disease burden and emergence of multi- and extensively drug-resistant  Salmonella  strains, it is becoming difficult to treat the infection with existing battery of antibiotics as we are not able to discover newer antibiotics at the same pace at which the pathogens are acquiring resistance. Though vaccines against  Salmonella  are available commercially, they have limited efficacy. Advancements in genome sequencing technologies and immunoinformatics approaches have solved the problem significantly by giving rise to a new era of vaccine designing, i.e. ‘Reverse engineering.’ Reverse engineering/vaccinology has expedited the vaccine identification process. Using this approach, multiple potential proteins/epitopes can be identified and constructed as a single entity to tackle enteric fever. This review provides details of reverse engineering approach and discusses various protein and epitope-based vaccine candidates identified using this approach against typhoidal  Salmonella . Reverse engineering approach holds great promise for developing strategies to tackle the pathogen(s) by overcoming the limitations posed by existing vaccines. Progressive advancements in the arena of reverse vaccinology, structural biology, and systems biology combined with an improved understanding of host–pathogen interactions are essential components to design new-generation vaccines.

Reverse engineering approach: a step towards a new era of vaccinology with special reference to Salmonella