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Science: Immune history profoundly affects broadly protective B cell responses to influenza

tetano

Editor, Senior Moderator
Sci Transl Med. 2015 Dec 2;7(316):316ra192. doi: 10.1126/scitranslmed.aad0522.
[h=1]Immune history profoundly affects broadly protective B cell responses to influenza.[/h] Andrews SF[SUP]1[/SUP], Huang Y[SUP]1[/SUP], Kaur K[SUP]2[/SUP], Popova LI[SUP]1[/SUP], Ho IY[SUP]1[/SUP], Pauli NT[SUP]2[/SUP], Henry Dunand CJ[SUP]1[/SUP], Taylor WM[SUP]1[/SUP], Lim S[SUP]1[/SUP], Huang M[SUP]1[/SUP], Qu X[SUP]1[/SUP], Lee JH[SUP]1[/SUP], Salgado-Ferrer M[SUP]1[/SUP], Krammer F[SUP]3[/SUP], Palese P[SUP]4[/SUP], Wrammert J[SUP]5[/SUP], Ahmed R[SUP]5[/SUP], Wilson PC[SUP]6[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Generating a broadly protective influenza vaccine is critical to global health. Understanding how immune memory influences influenza immunity is central to this goal. We undertook an in-depth study of the B cell response to the pandemic 2009 H1N1 vaccine over consecutive years. Analysis of monoclonal antibodies generated from vaccine-induced plasmablasts demonstrated that individuals with low preexisting serological titers to the vaccinating strain generated a broadly reactive, hemagglutinin (HA) stalk-biased response. Higher preexisting serum antibody levels correlated with a strain-specific HA head-dominated response. We demonstrate that this HA head immunodominance encompasses poor accessibility of the HA stalk epitopes. Further, we show polyreactivity of HA stalk-reactive antibodies that could cause counterselection of these cells. Thus, preexisting memory B cells against HA head epitopes predominate, inhibiting a broadly protective response against the HA stalk upon revaccination with similar strains. Consideration of influenza exposure history is critical for new vaccine strategies designed to elicit broadly neutralizing antibodies.
Copyright ? 2015, American Association for the Advancement of Science.


PMID: 26631631 [PubMed - in process]
 
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