title: Boosted Influenza-Specific T Cell Responses after H5N1 Pandemic Live Attenuated Influenza Virus Vaccination.
abstract: BACKGROUND
  In a phase I clinical trial, a H5N1 pandemic live attenuated influenza virus (pLAIV) VN2004 vaccine bearing avian influenza H5N1 hemagglutinin (HA) and NA genes on the A/Ann Arbor cold-adapted vaccine backbone displayed very restricted replication. We evaluated T cell responses to H5N1 pLAIV vaccination and assessed pre-existing T cell responses to determine whether they were associated with restricted replication of the H5N1 pLAIV.
  
  
  METHODS
  ELISPOT assays were performed using pools of overlapping peptides spanning the entire H5N1 proteome and the HA proteins of relevant seasonal H1N1 and H3N2 viruses. We tested stored peripheral blood mononuclear cells (PBMCs) from 21 study subjects who received two doses of the H5N1 pLAIV. The PBMCs were collected 1 day before and 7 days after the first and second pLAIV vaccine doses, respectively.
  
  
  RESULTS
  T cell responses to conserved internal proteins M and NP were significantly boosted by vaccination (p = 0.036). In addition, H5N1 pLAIV appeared to preferentially stimulate and boost pre-existing seasonal influenza virus HA-specific T cell responses that showed low cross-reactivity with the H5 HA. We confirmed this observation by T cell cloning and identified a novel HA-specific epitope. However, we did not find any evidence that pre-existing T cells prevented pLAIV replication and take.
  
  
  CONCLUSIONS
  We found that cross-reactive T cell responses could be boosted by pLAIV regardless of the induction of antibody. The impact of the "original antigenic sin" phenomenon in a subset of volunteers, with preferential expansion of seasonal influenza-specific but not H5N1-specific T cell responses merits further investigation.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford , Oxford , UK.
authors.forename: YanChun
authors.initials: Y
authors.lastname: Peng
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford , Oxford , UK ; Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University , Beijing , China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Wang
authors.affiliation: Center for Immunization Research, Johns Hopkins University Bloomberg School of Public Health , Baltimore, MD , USA.
authors.forename: Kawsar
authors.initials: K
authors.lastname: Talaat
authors.affiliation: Center for Immunization Research, Johns Hopkins University Bloomberg School of Public Health , Baltimore, MD , USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Karron
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford , Oxford , UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Powell
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University , Beijing , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford , Oxford , UK.
authors.forename: Danning
authors.initials: D
authors.lastname: Dong
authors.affiliation: Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Disease, National Institutes of Health , Bethesda, MD , USA.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Luke
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford , Oxford , UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: McMichael
authors.affiliation: Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Disease, National Institutes of Health , Bethesda, MD , USA.
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford , Oxford , UK.
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
keywords: H5N1; LAIV; T cells; antigenic sin; epitope; influenza; peptide; vaccine