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Table 1.
Historical milestones tracking the impact of new technologies on vaccine discovery and design
Milestone yearsApproach to discover and design vaccinesTechnologies and descriptionComments and references
1796 Classical vaccinology Growing microorganisms: Growth of microorganisms allows making killed and live-attenuated vaccines or to discover antigens used for subunit vaccines. 1796: Jenner starts growing cowpox in cows (Willis, 1997; Baxby, 1999), marking the beginning of vaccinology. 
1995   1995: Venter publishes the first sequencing of the entire genome from a bacterium (Fleischmann et al., 1995).  
2000 Reverse vaccinology Genomics, high-throughput protein expression, and animal models: Vaccine antigens are discovered using the genomic information without the need for growing microorganisms. Antigens selected in silico are expressed and screened in animal models. 2000: The first vaccine candidates based on antigens discovered by genomics are reported (Pizza et al., 2000). 
2012   2012: The first genome-based vaccine receives regulatory approval (European Medicines Agency, 2012). 
2002    2002: Burton proposes to use human mAbs to design new vaccines (Burton, 2002).  
2008 Reverse vaccinology 2.0 Genomics, high-throughput protein expression, animal models, human monoclonals, B cell repertoire deep sequencing, proteomics, and structure-based antigen design: Genomics is used not only for antigen discovery, but also for antigen expression, conservation, and for epidemiology. Human monoclonals are used to identify protective antigens/epitopes. Structural characterization of the Ab–antigen complex is used to instruct antigen design. 2008: Dormitzer, Ulmer, and Rappuoli propose the term "structural vaccinology" to identify the emerging structure-based antigen design (Dormitzer et al., 2008). 
2013   2013: Graham and Kwong first report that RSV pre-fusion F antigen successfully derived from structure-based design is protective in the animal model (McLellan et al., 2013a). 
Milestone yearsApproach to discover and design vaccinesTechnologies and descriptionComments and references
1796 Classical vaccinology Growing microorganisms: Growth of microorganisms allows making killed and live-attenuated vaccines or to discover antigens used for subunit vaccines. 1796: Jenner starts growing cowpox in cows (Willis, 1997; Baxby, 1999), marking the beginning of vaccinology. 
1995   1995: Venter publishes the first sequencing of the entire genome from a bacterium (Fleischmann et al., 1995).  
2000 Reverse vaccinology Genomics, high-throughput protein expression, and animal models: Vaccine antigens are discovered using the genomic information without the need for growing microorganisms. Antigens selected in silico are expressed and screened in animal models. 2000: The first vaccine candidates based on antigens discovered by genomics are reported (Pizza et al., 2000). 
2012   2012: The first genome-based vaccine receives regulatory approval (European Medicines Agency, 2012). 
2002    2002: Burton proposes to use human mAbs to design new vaccines (Burton, 2002).  
2008 Reverse vaccinology 2.0 Genomics, high-throughput protein expression, animal models, human monoclonals, B cell repertoire deep sequencing, proteomics, and structure-based antigen design: Genomics is used not only for antigen discovery, but also for antigen expression, conservation, and for epidemiology. Human monoclonals are used to identify protective antigens/epitopes. Structural characterization of the Ab–antigen complex is used to instruct antigen design. 2008: Dormitzer, Ulmer, and Rappuoli propose the term "structural vaccinology" to identify the emerging structure-based antigen design (Dormitzer et al., 2008). 
2013   2013: Graham and Kwong first report that RSV pre-fusion F antigen successfully derived from structure-based design is protective in the animal model (McLellan et al., 2013a). 
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