title: CD4+ T-cell expansion predicts neutralizing antibody responses to monovalent, inactivated 2009 pandemic influenza A(H1N1) virus subtype H1N1 vaccine.
abstract: BACKGROUND
  The ability of influenza vaccines to elicit CD4(+) T cells and the relationship between induction of CD4(+) T cells and vaccine-induced neutralizing antibody responses has been controversial. The emergence of swine-origin 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) provided a unique opportunity to examine responses to an influenza vaccine composed of both novel and previously encountered antigens and to probe the relationship between B-cell and T-cell responses to vaccination.
  
  
  METHODS
  We tracked CD4(+) T-cell and antibody responses of human subjects vaccinated with monovalent subunit A(H1N1)pdm09 vaccine. The specificity and magnitude of the CD4(+) T-cell response was evaluated using cytokine enzyme-linked immunosorbent spot assays in conjugation with peptide pools representing distinct influenza virus proteins.
  
  
  RESULTS
  Our studies revealed that vaccination induced readily detectable CD4(+) T cells specific for conserved portions of hemagglutinin (HA) and the internal viral proteins. Interestingly, expansion of HA-specific CD4(+) T cells was most tightly correlated with the antibody response.
  
  
  CONCLUSIONS
  These results indicate that CD4(+) T-cell expansion may be a limiting factor in development of neutralizing antibody responses to pandemic influenza vaccines and suggest that approaches to facilitate CD4(+) T-cell recruitment may increase the neutralizing antibody produced in response to vaccines against novel influenza strains.
authors.affiliation: Department of Pediatrics, Department of Pediatrics, Division of Infectious Diseases, University of Rochester Medical Center, Rochester, NY 14642, USA. jennifer_nayak@urmc.rochester.edu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Nayak
authors.forename: Theresa F
authors.initials: TF
authors.lastname: Fitzgerald
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Richards
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yang
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Sant
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D058873:Pandemics; D011237:Predictive Value of Tests; D015164:Vaccines, Inactivated / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016056:Immunodominant Epitopes; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated