title: H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.
abstract: BACKGROUND
  During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection.
  
  
  RESULTS
  To study hemagglutinin (HA) antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV) and compared them to the plasma cell repertoires of subjects experimentally infected (EI) with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject.
  
  
  CONCLUSIONS
  The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains.
authors: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America. moody007@mc.duke.edu
authors: M Anthony
authors: MA
authors: Moody
authors: Ruijun
authors: R
authors: Zhang
authors: Emmanuel B
authors: EB
authors: Walter
authors: Christopher W
authors: CW
authors: Woods
authors: Geoffrey S
authors: GS
authors: Ginsburg
authors: Micah T
authors: MT
authors: McClain
authors: Thomas N
authors: TN
authors: Denny
authors: Xi
authors: X
authors: Chen
authors: Supriya
authors: S
authors: Munshaw
authors: Dawn J
authors: DJ
authors: Marshall
authors: John F
authors: JF
authors: Whitesides
authors: Mark S
authors: MS
authors: Drinker
authors: Joshua D
authors: JD
authors: Amos
authors: Thaddeus C
authors: TC
authors: Gurley
authors: Joshua A
authors: JA
authors: Eudailey
authors: Andrew
authors: A
authors: Foulger
authors: Katherine R
authors: KR
authors: DeRosa
authors: Robert
authors: R
authors: Parks
authors: R Ryan
authors: RR
authors: Meyerhoff
authors: Jae-Sung
authors: JS
authors: Yu
authors: Daniel M
authors: DM
authors: Kozink
authors: Brice E
authors: BE
authors: Barefoot
authors: Elizabeth A
authors: EA
authors: Ramsburg
authors: Surender
authors: S
authors: Khurana
authors: Hana
authors: H
authors: Golding
authors: Nathan A
authors: NA
authors: Vandergrift
authors: S Munir
authors: SM
authors: Alam
authors: Georgia D
authors: GD
authors: Tomaras
authors: Thomas B
authors: TB
authors: Kepler
authors: Garnett
authors: G
authors: Kelsoe
authors: Hua-Xin
authors: HX
authors: Liao
authors: Barton F
authors: BF
authors: Haynes
mesh_terms: D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000276:immunology; D000918:Antibody Specificity; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000302:isolation & purification*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020349:Surface Plasmon Resonance
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines