Abstract
The influenza virus-host interaction is a classic arms race. The recurrent and evolving nature of the influenza virus family allows a single host to be infected several times. Locked in co-evolution, recurrent influenza virus infection elicits continual refinement of the host immune system. Here we give historical context of circulating influenza viruses to understand how the individual immune history is mirrored by the history of influenza virus circulation. Original Antigenic Sin was first proposed as the negative influence of the host’s first influenza virus infection on the next and Imprinting modernizes Antigenic Sin incorporating both positive and negative outcomes. Building on imprinting, we refer to preimmunity as the continual refinement of the host immune system with each influenza virus infection. We discuss imprinting and the interplay of influenza virus homology, vaccination, and host age establishing preimmunity. We outline host signatures and outcomes of tandem infection according to the sequence of virus and classify these relationships as monosubtypic homologous, monosubtypic heterologous, heterosubtypic, or heterotypic sequential infections. Finally, the preimmunity knowledge gaps are highlighted for future investigation. Understanding the effects of antigenic variable recurrent influenza virus infection on immune refinement will advance vaccination strategies, as well as pandemic preparedness.
Highlights
Influenza Viruses are the Archetype Emerging and Re-Emerging VirusesInfluenza virus is not a single virus but, instead, a family of constantly changing virus strains.The family is defined by four virus types that are divided into subtypes or lineages
Since the immune responses of each new infection is dictated by individual preimmunity, we look to the past to predict the outcome of the infection
Taken together with the H1N1 Monsubtypic homologous (MsHo) drift study [88], the results suggest that humoral immune responses may differ according to the drifting subtype
Summary
Influenza virus is not a single virus but, instead, a family of constantly changing virus strains. Since influenza viruses cycle yearly in the human population and the immunity gained from previous infection is not life-long [6], people are exposed to influenza viruses recurrently. This means that everyone, with the exception of newborn infants, has an influenza immune history. Dr Thomas Francis Jr. suggested that a person’s first influenza virus infection would be deleterious to the clinical outcome of the infection and referred to this as Original Antigenic Sin (OAS) [7] The mechanisms of this outcome were regulated by memory immune responses.
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