A master thesis from Aalborg University
Characterising Recent H1N1 Glycosylation and Its Implication for Influenza A Vaccine Effectiveness
[Karakterisering af Nylig H1N1 Glykosylation og Dennes Implikation for Influenza A Vaccine Effektivitet]
Author(s)
Term
4. term
Education
Publication year
2017
Submitted on
2017-06-11
Pages
100 pages
Abstract
Influenza sæsonen 2015-2016 oplevede et fald i effektiviteten hos influenza A vaccinen, hvilket potentielt skyldes tilføjelsen af nye glykosylationer i hæmagglutinin (HA) hos H1N1. 23 influenza A virus (IAV) prøver, spredt over fem influenza sæsoner med rod i det pandemiske udbrud i 2009 (A(H1N1)pdm2009), bliver karakteriseret antigenisk vha. immunologiske eksperimenter og sekvensanalyser, for at bestemme hvorvidt nye glykosyleringer er ansvarlige for faldet i IAV vaccine effektiviteten. Derudover bliver IAV prøverne karakteriseret med immunoblots og overfladeplasmonresonans målinger for at kvantificere deres antigene forskelle. Seks ud af de otte undersøgte IAV prøver fra 2015-2016 sæsonen har tilføjet en ny glykosyleringsposition ved Ser179 hos HA, grundet et skift til Asn. Undersøgelse af resistance mod antistoffer groet med udgangspunkt i A(H1N1)pdm2009 viste, at der var en tendens for højere fold-ændringsfaktorer i IAV prøver med Ser179!Asn substitutionen, hvilket er observeret i prøverne A/Denmark/30/16 og A/Denmark/46/16. Begge prøver forventes glykosylerede, hvilket udgører en sandsynlig begrundelse for faldet i IAV vaccine effektiviteten. Mere forståelse er nødvendigt, hvis overfladeplasmonresonans målinger skal benyttes til at analysere antigene egenskaber. Implementering af denne teknik inden for influenza vaccine immunologi kræver dybdegående analyse af analytens komposition og type.
The flu season of 2015-2016 saw a decrease in the effectiveness of the influenza A vaccine, potentially caused by the introduction of new glycosylations in the hemagglutinin (HA) of H1N1. 23 seasonal influenza A virus (IAV) samples, spread across five seasons with root in the 2009 pandemic H1N1 outbreak (A(H1N1)pdm2009), are antigenically characterised by immunological assays and sequence analysis, to determine whether glycosylation is responsible for the decrease in vaccine effectiveness. Similarly, characterisation with immunoblots and surface plasmon resonance (SPR) measurements is attempted to quantify antigenic differences. Six out of eight of the surveyed IAV samples from the 2015-2016 season have new glycosylation sites at Ser179 of HA, caused by a substitution to Asn. Investigating resistance towards antibodies raised to A(H1N1)pdm2009 by means of hemagglutiniation inhibition assays unveils a predominance for incremented fold-change factors in IAV samples harbouring the Ser179!Asn substitution, as observed in IAV samples A/Denmark/30/16 and A/Denmark/46/16. Both samples are considered to be glycosylated, which makes it a probable explanation for the decrease in influenza A vaccine effectiveness. Using SPR as a characterization technique of antigenic properties of IAVs requires refining. Studying analyte type and composition is the first step in implementing this method for influenza vaccine immunology.
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