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Imprinting of Repeated Influenza A/H3 Exposures on Antibody Quantity and Antibody Quality: Implications on Seasonal Vaccine Strain Selection and Vacci

tetano

Editor, Senior Moderator
Clin Infect Dis. 2018 Apr 17. doi: 10.1093/cid/ciy327. [Epub ahead of print]
[h=1]Imprinting of Repeated Influenza A/H3 Exposures on Antibody Quantity and Antibody Quality: Implications on Seasonal Vaccine Strain Selection and Vaccine Performance.[/h] Kosikova M[SUP]1[/SUP], Li L[SUP]2[/SUP], Radvak P[SUP]1[/SUP], Ye Z[SUP]1[/SUP], Wan XF[SUP]2[/SUP], Xie H[SUP]1[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] [h=4]Background:[/h] Reduced seasonal influenza vaccine effectiveness (VE) was observed in individuals who received repeated annual vaccinations. Pre-existing influenza antibody levels were also found inversely correlated with post-vaccination titers. These reports suggest that pre-existing immunity may affect contemporary seasonal vaccine performance.
[h=4]Methods:[/h] Influenza A/H3 specific cross-reactivity of post-vaccination sera from humans with or without pre-existing immunity was assessed by hemagglutination inhibition (HAI) assay. Ferret antisera induced by repeated H3 exposures were also subjected to HAI, antibody affinity and antibody avidity analyses.
[h=4]Results:[/h] Human post-vaccination sera derived from subjects with or without pre-existing immunity showed different cross-reactivity against H3 variant viruses. Similarly, the breadth of cross-reactive ferret antibodies induced by repeated H3 exposures was also broadened. Antigenic differences between H3 viruses characterized by ferret antisera became smaller as the number of exposures increased. Although repeated H3 exposures induced "Original Antigenic Sin" phenomena in HAI titers against later exposed viruses, resultant ferret antibodies showed gradually enhanced avidity for different H3/HA. Increased antibody avidity was found inversely correlated with decreased antigenic differences among H3 viruses characterized.
[h=4]Conclusions:[/h] Our results suggest that repeated H3 exposures imprinted not only antibody quantity but also antibody quality. The "na?ve" ferret model currently used for vaccine strain selection does not recapitulate the complexity of human pre-existing immunity. Vaccine strains identified hereby may not provide coverage sufficient for those who were frequently infected and/or vaccinated leading to reduced VE observed.


PMID: 29672713 DOI: 10.1093/cid/ciy327
 
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