Vaccines: from empirical development to rational design

Abstract

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.

Figure 1. Optimizing the design for more efficient vaccines.

Modern vaccinology focuses on the development of subunit vaccines to maximize efficacy and minimize risks in healthy and immune-compromised individuals. Different enabling technologies and knowledge contribute towards the rational design of formulations that would not only exhibit improved performance but also reduce the time and costs associated with preclinical and clinical development. Promising approaches/enabling factors and roadblocks are highlighted in green and pink, respectively.