title: Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.
abstract: OBJECTIVE
  We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.
  
  
  METHODS
  Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1.
  
  
  RESULTS
  At entry, 26 (29%) subjects had pH1N1 protective HAI titers (≥1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05), but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets.
  
  
  CONCLUSIONS
  HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent on B-cell subset distribution, but not on CD4 counts or viral load.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00992836.
authors.affiliation: Pediatric Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Curtis
authors.affiliation: Statistical and Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Petronella
authors.initials: P
authors.lastname: Muresan
authors.affiliation: SUNY Stony Brook, Stony Brook, New York, United States of America.
authors.forename: Sharon
authors.initials: S
authors.lastname: Nachman
authors.affiliation: Statistical and Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Terence
authors.initials: T
authors.lastname: Fenton
authors.affiliation: Pediatric Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Richardson
authors.affiliation: Pediatric Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Teresa
authors.initials: T
authors.lastname: Dominguez
authors.affiliation: St. Jude's Children's Hospital, Memphis, Tennessee, United States of America.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Flynn
authors.affiliation: University of California San Diego, La Jolla, California, and Rady Children's Hospital, San Diego, California, United States of America.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Spector
authors.affiliation: Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Coleen K
authors.initials: CK
authors.lastname: Cunningham
authors.affiliation: Frontier Science and Technology Research Foundation, Amherst, New York, United States of America.
authors.forename: Anthony
authors.initials: A
authors.lastname: Bloom
authors.affiliation: Pediatric Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado, United States of America; Departments of Medicine and Pathology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines; D008297:Male; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007252:Influenza Vaccines