Characterising Recent H1N1 Glycosylation and Its Implication for Influenza A Vaccine Effectiveness
Translated title
Karakterisering af Nylig H1N1 Glykosylation og Dennes Implikation for Influenza A Vaccine Effektivitet
Author
Bolotakis, Alexander Sivesgaard
Term
4. term
Education
Publication year
2017
Submitted on
2017-06-11
Pages
100
Abstract
I influenzasæsonen 2015–2016 virkede vaccinen mod influenza A dårligere end forventet. En mulig forklaring er, at nogle H1N1‑virus fik ekstra sukkermolekyler (glycosyleringer) på hemagglutinin (HA), det overfladeprotein som antistoffer genkender. Vi undersøgte 23 sæsonprøver af influenza A(H1N1)pdm2009 indsamlet over fem sæsoner. Med immuntests og gensekventering, samt ved at afprøve immunblot og overfladeplasmonresonans (SPR), vurderede vi, om nye glycosyleringer kunne forklare det lavere beskyttelsesniveau ved at måle antigeniske forskelle (hvordan immunforsvaret "ser" virus). Blandt de otte virus fra 2015–2016 havde seks en ændring i HA på position 179 (serin til asparagin), som skaber et nyt sted, hvor et sukker kan binde. I hæmagglutinationsinhiberingstests—standardmålinger af, hvor godt antistoffer blokerer virus—var virus med denne ændring oftere dårligere hæmmet af antistoffer rettet mod 2009‑H1N1. Dette sås f.eks. for stammerne A/Denmark/30/16 og A/Denmark/46/16. Begge vurderes at være glycosylerede, hvilket gør glycosylering til en sandsynlig forklaring på den lavere vaccineeffektivitet i den sæson. Vores forsøg på at bruge SPR til at kvantificere de antigeniske forskelle viser, at metoden skal finjusteres. Valg og karakterisering af analytten (det, der strømmer over sensoren) er et vigtigt første skridt mod at bruge SPR i influenzavaccineforskning.
During the 2015–2016 flu season, the influenza A vaccine was less effective than expected. One possible reason is that some H1N1 viruses added extra sugars (glycosylations) to hemagglutinin (HA), the surface protein targeted by antibodies. We examined 23 seasonal influenza A(H1N1)pdm2009-related viruses collected over five seasons. Using immunological tests and gene sequencing, and exploring immunoblots and surface plasmon resonance (SPR), we assessed whether new glycosylations could explain the drop in protection by measuring antigenic differences (how the immune system "sees" the virus). Among the eight viruses from 2015–2016, six had a change at HA position 179 (serine to asparagine), which creates a new site where a sugar can attach. In hemagglutination inhibition tests—standard assays that measure how well antibodies block the virus—viruses with this change were more often less inhibited by antibodies raised against the 2009 H1N1 strain. This pattern was seen, for example, in strains A/Denmark/30/16 and A/Denmark/46/16. Both are considered glycosylated, making glycosylation a plausible explanation for the reduced vaccine effectiveness that season. Our attempts to use SPR to quantify these antigenic differences indicate that the technique needs further refinement. Choosing and characterizing the analyte (what is flowed over the sensor) is an important first step toward applying SPR in influenza vaccine studies.
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