Several human vaccinations were created at the end of the nineteenth century, Smallpox, rabies, plague, cholera, and typhoid vaccinations are among them. Major things to acknowledge before vaccine preparation is that we have to isolate the antibody firstly which our body has produced against the pathogen and what is the composition of that antibody and also the structure of an antibody. A vaccine is administered to induce immunity in an individual’s body. Typically, the manufacture of vaccine uses viral or bacterial antigen in it. It may be killed or attenuated vaccine (live but less virulent). The foremost step to produce a vaccine is to select the strains for the vaccine and to culture the strain or microorganism. These two steps are collectively known as the upstream process. This is further followed by isolation and purification of the microorganism and then after the inactivation of the organism which is used for vaccine preparation formulation of vaccine begins. The last step is to check quality control and then further lot release; all of these steps are included in downstream processing. Mostly used vaccines lack efficiency, potency and safety. To take the vaccine preparation to next level, the introduction of monoclonal antibodies, recombinant DNA, and protein engineering have been accelerated knowledge of pathogenic mechanisms. This review provides a new approach to the development of the succeeding generation of vaccines.