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Abstract
I will offer a conceptual analysis of different notions of structure and function of viral immunogens and of different structure-function relationships. My focus will then be on the mechanisms by which the desired immune response is induced and why strategies based on three-dimensional molecular antigen structures and their rational design are limited in their ability to induce the desired immunogenicity. I will look at the mechanisms of action of adjuvants (thus the wordplay with Janeway’s “immunologist’s dirty little secret”). Strategies involving adjuvants and other (more successful) vaccination strategies rely on taking into account activities and functions (“what is going on”), and not just the structures involved (“who is there”), in binding in a “lock and key” fashion. Functional patterns as well as other organizational and temporal patterns, I will argue, are crucial for inducing the desired immune response and immunogenicity. The 3D structural approach by itself has its benefits – and its limits, which I want to highlight by this philosophical analysis, pointing out the importance of structure-function relationships. Different functional aspects such as antigenicity, immunogenicity, and immunity need to be kept separate and cannot be reduced to three-dimensional structures of vaccines. Taking into account different notions of structure and function and their relationships might thus advance our understanding of the immune system and rational HIV vaccine design, to which end philosophy can provide useful tools.
Highlights
In his seminal 1989 paper, Charles A
With systems immunology and systems vaccinology still in their infancy, we are far from such an extent of knowledge and understanding to venture with such an approach. It is doubtful whether the required completeness of knowledge about complex immune system interactions will ever be of an adequate quality to understand, let alone design, vaccines based on the s trorg of these networks and their components and activities. It is a different kind of reductionism than basing everything solely on str3D, there is not much reason to be too optimistic about such attempts succeeding in the near future in developing HIV vaccines
A better understanding of structure-function relationships might advance rational HIV vaccine design, open up other pathways of prevention and therapy, and help avoiding theoretical misconceptions that have posed a barrier in other areas of biology and medicine
Summary
In his seminal 1989 paper, Charles A. It is doubtful whether the required completeness of knowledge about complex immune system interactions will ever be of an adequate quality to understand, let alone design, vaccines based on the s trorg of these networks and their components and activities It is a different kind of reductionism than basing everything solely on str3D, there is not much reason to be too optimistic about such attempts succeeding in the near future in developing HIV vaccines. It is not out of the question that major steps will be made in that direction, but it will be rather by “accident”, i.e., empirically by trial and error rather than based on knowing the primitive structural and functional components of these immune systems. For all of these alternative approaches and for keeping the relevant processes apart, an improved understanding of structure-function relationships should be helpful – at the very least, to avoid falling for certain conceptual misunderstandings that take a simplistic, reductionist view on structure and function
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