Vaccines: from empirical development to rational design

PLoS Pathog. 2012;8(11):e1003001. doi: 10.1371/journal.ppat.1003001. Epub 2012 Nov 8.


Infectious diseases are responsible for an overwhelming number of deaths worldwide and their clinical management is often hampered by the emergence of multi-drug-resistant strains. Therefore, prevention through vaccination currently represents the best course of action to combat them. However, immune escape and evasion by pathogens often render vaccine development difficult. Furthermore, most currently available vaccines were empirically designed. In this review, we discuss why rational design of vaccines is not only desirable but also necessary. We introduce recent developments towards specifically tailored antigens, adjuvants, and delivery systems, and discuss the methodological gaps and lack of knowledge still hampering true rational vaccine design. Finally, we address the potential and limitations of different strategies and technologies for advancing vaccine development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens / immunology
  • Humans
  • Infection Control*
  • Vaccination
  • Vaccines / immunology*


  • Antigens
  • Vaccines

Grants and funding

This work was supported in part by grants from the EU (PANFLUVAC, TRANSVAC); BMBF in the context of the programs Gerontosys 2 (Gerontoshield), EuroNanoMed (HCVAX) and ERANetRUS (HCRUS), and the Helmholtz Association (IG-SCID). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.