Immunogenetics of seasonal influenza vaccine response

Abstract

Seasonal influenza causes significant morbidity, mortality, and economic costs. Vaccines against influenza, though both safe and effective, are imperfect. Notably, these vaccines result in significant immune response variability across the population. The mechanism for this variability, in part, appears to lie in the polymorphisms of key immune response genes. Despite the importance of this variability, little in the way of genetic polymorphisms and its association with vaccine immune response to viral vaccines has been performed. Herein, we review and synthesize what is known about the immune response pathway and influenza viral immunity and then present original data from our laboratory on the immunogenetic relationships between HLA, cytokine and cytokine receptor gene polymorphisms and the variations in humoral immune response to inactivated seasonal influenza vaccine. Finally, we propose that a better understanding of vaccine immunogenetics offers insight towards the development of better influenza vaccines.

Figure

Immune response pathway representing a set of candidate gene classes encompassing both innate and adaptive immune response genes to influenza virus. These genes include: 1) viral binding surface receptor and innate receptor genes (natural killer receptors, Toll-like receptors, retinoic acid-inducible gene I-like receptors, and protein kinase receptors) for influenza virus, which regulate viral recognition and detection of infection, 2) HLA (class I and class II) genes that bind and present naturally processed viral peptides to T cells, 3) cytokines and their receptor genes that serve to shape and control both humoral and cellular immune responses responsible for viral neutralization and clearance, 4) adhesion molecule and chemokines and their receptor genes that serve to regulate the chemotaxis and infiltration of leucocytes into infected tissues, and 5) immune effector molecules (mannose binding lectins, perforin, granzymes) that serve to neutralize virus and mediate cell cytotoxicity.