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

Publication ,  Journal Article
Bajic, G; Maron, MJ; Adachi, Y; Onodera, T; McCarthy, KR; McGee, CE; Sempowski, GD; Takahashi, Y; Kelsoe, G; Kuraoka, M; Schmidt, AG
Published in: Cell Host Microbe
June 12, 2019

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).

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

June 12, 2019

Volume

25

Issue

6

Start / End Page

827 / 835.e6

Location

United States

Related Subject Headings

  • Survival Analysis
  • Protein Conformation
  • Protein Binding
  • Polysaccharides
  • Orthomyxoviridae Infections
  • Mice, Inbred BALB C
  • Influenza A Virus, H3N2 Subtype
  • Immunology
  • Immunization, Passive
  • Hemagglutinin Glycoproteins, Influenza Virus
 

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Bajic, G., Maron, M. J., Adachi, Y., Onodera, T., McCarthy, K. R., McGee, C. E., … Schmidt, A. G. (2019). Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope. Cell Host Microbe, 25(6), 827-835.e6. https://doi.org/10.1016/j.chom.2019.04.003
Bajic, Goran, Max J. Maron, Yu Adachi, Taishi Onodera, Kevin R. McCarthy, Charles E. McGee, Gregory D. Sempowski, et al. “Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope.Cell Host Microbe 25, no. 6 (June 12, 2019): 827-835.e6. https://doi.org/10.1016/j.chom.2019.04.003.
Bajic G, Maron MJ, Adachi Y, Onodera T, McCarthy KR, McGee CE, et al. Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope. Cell Host Microbe. 2019 Jun 12;25(6):827-835.e6.
Bajic, Goran, et al. “Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope.Cell Host Microbe, vol. 25, no. 6, June 2019, pp. 827-835.e6. Pubmed, doi:10.1016/j.chom.2019.04.003.
Bajic G, Maron MJ, Adachi Y, Onodera T, McCarthy KR, McGee CE, Sempowski GD, Takahashi Y, Kelsoe G, Kuraoka M, Schmidt AG. Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope. Cell Host Microbe. 2019 Jun 12;25(6):827-835.e6.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

June 12, 2019

Volume

25

Issue

6

Start / End Page

827 / 835.e6

Location

United States

Related Subject Headings

  • Survival Analysis
  • Protein Conformation
  • Protein Binding
  • Polysaccharides
  • Orthomyxoviridae Infections
  • Mice, Inbred BALB C
  • Influenza A Virus, H3N2 Subtype
  • Immunology
  • Immunization, Passive
  • Hemagglutinin Glycoproteins, Influenza Virus