Exploiting the Redundancy in the Immune System

The fields of vaccinology and immunology have had a long-standing and complicated relationship. The view that vaccinology is a branch of immunology is more perception than reality. Vaccinology is older, practical, and often idio-syncratic, with its prime focus on the development of functional vaccines that protect a host against a particular microbe. Immunology is younger, conceptual, and strives to explain how a remarkably complex system recognizes and protects against internal and external threats without committing suicide. Vaccinology has been largely microbe centered , clinically successful, and mostly empirical, whereas immunology has been largely host-centered, having struggled to translate its theoretical success and potential into clinical applicability. In this commentary, we examine the divide between vaccinology and immunology and put forth the view that vaccines often protect against infectious diseases by eliciting 'unnatural' immunity: immune responses that differ from and may even counteract those that arise during the development of natural immunity to a microbe. The success of vaccinology, often achieved through em-piricism, poses a challenge to the theses that vaccine design should be centered around the study of the immune response and that an effective vaccine should recapitulate the normal immune response to the relevant microbe. The eradication of smallpox by vaccination with vaccinia virus is probably the greatest achievement of vaccinology. However, this success also illustrates the tension between vaccinology and immunology, because smallpox (caused by variola virus) was prevented by inoculating humans with a different virus, the agent of cowpox (vaccinia virus). The prevention of variola by deliberate infection with a different virus (vaccinia) would appear to run counter to the tenet that specificity is essential for protective immunity , which has been central to immunological thought for over a century. Although vaccinia-induced protection against variola can be explained by antigenic mimicry, or similarities between the antigenic determinants of the vari-ola and vaccinia viruses, antigenic cross-reactivity is often viewed by immunologists as an exception to the central importance of specificity in immunological responses. In fact, the immunological cross-reactivity which allows the immune response to vaccinia virus to protect against variola virus is not a general phenomenon. One herpes virus may not confer protection against another herpes virus and immunity to one serotype of strains of Streptococcus pneumoniae does not confer immunity to another. Cross-reactivity has at times been viewed as a deviation from the immunological ideal, particularly when it is held responsible for autoimmu-nity and Pauls Erhlich's ' …