#Influenza #Antigen #Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope (Cell Host Microbe, abstract)

[Source: Cell, Host & Microbe, full page: (LINK). Abstract, edited.]

Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope

Goran Bajic, Max J. Maron, Yu Adachi, Taishi Onodera, Kevin R. McCarthy, Charles E. McGee, Gregory D. Sempowski, Yoshimasa Takahashi, Garnett Kelsoe, Masayuki Kuraoka, Aaron G. Schmidt

Published: May 16, 2019 / DOI: https://doi.org/10.1016/j.chom.2019.04.003

 

Highlights

  • Hyperglycosylation of hemagglutinin (HA) does not dampen serum and GC responses
  • Hyperglycosylation of HA changes patterns of immunodominance
  • Glycan addition restricts antibody repertoire to a subdominant epitope
  • Antibodies targeting this occluded epitope on HA protect against viral challenge

 

Summary

Viral glycoproteins are under constant immune surveillance by a host’s adaptive immune responses. Antigenic variation including glycan introduction or removal is among the mechanisms viruses have evolved to escape host immunity. Understanding how glycosylation affects immunodominance on complex protein antigens may help decipher underlying B cell biology. To determine how B cell responses can be altered by such modifications, we engineered glycans onto the influenza virus hemagglutinin (HA) and characterized the molecular features of the elicited humoral immunity in mice. We found that glycan addition changed the initially diverse antibody repertoire into an epitope-focused, genetically restricted response. Structural analyses showed that one antibody gene family targeted a previously subdominant, occluded epitope at the head interface. Passive transfer of this antibody conferred Fc-dependent protection to influenza virus-challenged mice. These results have potential implications for next-generation viral vaccines aimed at directing B cell responses to preferred epitope(s).

Keywords: immunogen design – protein engineering – broadly neutralizing antibodies – influenza hemagglutinin

Keywords: Influenza A; Vaccines.

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gimi69

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.

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