title: Phase II trial in adults of concurrent or sequential 2009 pandemic H1N1 and 2009-2010 seasonal trivalent influenza vaccinations.
abstract: BACKGROUND
  During the 2009 influenza pandemic both seasonal and 2009 pandemic vaccines were recommended. We conducted a randomized trial of monovalent 2009-H1N1 vaccine and seasonal trivalent inactivated influenza vaccine (IIV3) given sequentially or concurrently to adults.
  
  
  METHODS
  Adults randomized to 4 study groups and stratified by age (18-64 and ≥65 years) received 1 dose of seasonal IIV3 or placebo and 2 doses of 2009-H1N1 vaccine or placebo in one of 4 combinations, i.e., H1N1+Placebo/H1N1+Placebo/IIV3 (HP/HP/V3), H1N1+IIV3/H1N1+Placebo/Placebo (HV3/HP/P), H1N1+Placebo/H1N1+IIV3/Placebo (HP/HV3/P), and IIV3+Placebo/H1N1+Placebo/H1N1 (V3P/HP/H). Intramuscular injections were given three times at 21 day intervals. Sera for antibody assays were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored.
  
  
  RESULTS
  Eight hundred-five (805) adults were enrolled. All combinations of vaccines were safe and well tolerated. In general, one dose of 2009-H1N1 and one dose of IIV3, regardless of sequence or concurrency of administration, were immunogenic in adults. There were no significant differences in geometric mean titers (GMT) or the proportions of subjects with ≥4-fold rise in antibody responses and titers ≥40 for any vaccine group or between age strata for 2009-H1N1 after the first or second dose, although the vaccine sequence affected the titers to the IIV3 antigens. Hemagglutination inhibition antibody (HAI) GMTs against 2009-H1N1 for the combined age strata 21 days after the first 2009-H1N1 dose were 190.4, 182.1, 232.9 and 157.5 for HP/HP/V3, HV3/HP/P, HP/HV3/P and V3P/HP/H, respectively. While IIV3 GMTs were adequate they were generally lower than the 2009-H1N1 GMTs. In a subset of subjects, there was good correlation between HAI and microneutralization (MN) titers (Spearman's correlation coefficient 0.92).
  
  
  CONCLUSIONS
  All vaccine combinations were generally well tolerated. Immune responses to one dose of 2009-H1N1 were adequate regardless of the sequence of vaccination in all age groups, but the sequence affected titers to IIV3 antigens.
authors.affiliation: Saint Louis University School of Medicine, United States. Electronic address: freyse@slu.edu.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, United States.
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, United States.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Brady
authors.affiliation: Baylor College of Medicine, United States.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Keitel
authors.affiliation: Baylor College of Medicine, United States.
authors.forename: Hana
authors.initials: H
authors.lastname: El Sahly
authors.affiliation: The Hope Clinic of the Emory Vaccine Center, Department of Medicine, Emory University School of Medicine, United States.
authors.forename: Nadine Georges
authors.initials: NG
authors.lastname: Rouphael
authors.affiliation: The Hope Clinic of the Emory Vaccine Center, Department of Medicine, Emory University School of Medicine, United States.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.affiliation: Baylor College of Medicine, United States.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.affiliation: The Hope Clinic of the Emory Vaccine Center, Department of Medicine, Emory University School of Medicine, United States.
authors.forename: Srilatha
authors.initials: S
authors.lastname: Edupuganti
authors.affiliation: Baylor College of Medicine, United States.
authors.forename: Shital M
authors.initials: SM
authors.lastname: Patel
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Dickey
authors.affiliation: Saint Louis University School of Medicine, United States.
authors.forename: Irene
authors.initials: I
authors.lastname: Graham
authors.affiliation: Saint Louis University School of Medicine, United States.
authors.forename: Edwin L
authors.initials: EL
authors.lastname: Anderson
authors.affiliation: Southern Research Institute, United States.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Noah
authors.affiliation: The EMMES Corporation, United States.
authors.forename: Heather
authors.initials: H
authors.lastname: Hill
authors.affiliation: The EMMES Corporation, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Wolff
authors.affiliation: Saint Louis University School of Medicine, United States.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Belshe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007115:Immunization Schedule; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D014611:Vaccination / Q000009:adverse effects / Q000379:methods*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D010919:Placebos
keywords: 2009-H1N1; Adults; Concurrent; Elderly; HAI; Influenza vaccine; Microneutralization; Pandemic; Seasonal IIV3; Sequential