The time point at which this saturation occurs depends on the parameters (particularly, highersand lowerresult in faster saturation). to this epitope following immunization. We explore strategies for boosting of antibodies to conserved epitopes and generating broadly protective immunity to multiple strains. Keywords:influenza, strain-variation, humoral immunity, epitope masking model == 1. Introduction == We are rarely immunologically naiveeven at the time of birth we have pre-existing antibodies from our mothers. Prior immunity affects the responses both to infections and to vaccines. Understanding the rules for how pre-existing immunity modulates the immune response to subsequent infections is particularly important in the case of infections with influenza A computer virus which exhibits strain variation [1,2]. As a result of selection pressure from the immune system the influenza computer virus changes its surface antigens, which are the main target of humoral immunity. This allows hosts to be infected multiple occasions, each time with a new strain, over their lifespan, generating complex dynamics LY 3200882 LY 3200882 at the within-host (immunological) as well as at the epidemiological level. Influenza A is one of the best studied examples of viruses with strain variation and an ideal system to study the effects of prior immunity on subsequent contamination and vaccination. Both the virus and the immune response Rabbit polyclonal to SLC7A5 to it have been extensively characterized at the molecular, immunological and epidemiological levels [110]. Current influenza vaccines focus on the generation of antibodies to the surface proteins haemagglutinin (HA) and, to a lesser extent, neuraminidase. HA dominates the surface of the influenza virus, being four to five occasions more abundant than neuraminidase, and is the main target of the antibody response to influenza [1113]. HA is a homotrimeric integral membrane glycoprotein with a distinct head and stem structure [14]. The head of HA has about five highly variable epitopes, and the stem has fewer epitopes which are relatively conserved [7]. Eighteen different HA subtypes (H1H18) have been identified in the zoonotic reservoir [1517], and typically one or two of subtypes H1, H2 and H3 circulate in the human population at any LY 3200882 given time [9]. The head region of HA changes dramatically between HA subtypes, and there is little cross-reactivity between antibodies to different HA heads. The stem region is relatively conserved between each of two phylogenetic groups (group 1 includes H1, H2, H5, H6, H8, H9, H11, H12, H13, H16, H17 and H18; and group 2 includes H3, H4, H7, H10, H14 and H15) [1517]. Antibodies to epitopes around the HA stem can be broadly cross-reactive and able to recognize other subtypes within a group and even between the two groups [1824]. Antigenic changes in influenza A are of two types, antigenic drift and antigenic shift. Antigenic drift is responsible for seasonal outbreaks and involves a gradual change in antibody binding epitopes on the head of HA within a given subtype [2]. This allows the new viruses to escape the antibodies generated following contamination or vaccination with prior computer virus strains. Antigenic shift is responsible for relatively rare pandemics and involves replacement of the current circulating HA with a different subtype typically originating from zoonotic reservoirs [9]. Consequently, antigenic shift results in much larger changes to the HA head region in comparison with antigenic drift. Over the lifespan, an individual gets infected about a dozen occasions, predominantly by drift variants of a given subtype [25] and occasionally by new subtypes [9]. It was shown that for a given individual, the.