title: Safety and Immunogenicity of Cell Culture-Derived A/H3N2 Variant Influenza Vaccines: A Phase I Randomized, Observer-Blind, Dose-Ranging Study.
abstract: BACKGROUND
  A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important.
  
  
  METHODS
  In this phase I, randomized, observer-blind, dose-ranging study, 627 healthy subjects ≥ 3 years of age were randomized to receive 2 vaccinations with H3N2c cell-culture-derived vaccine doses containing 3.75 µg, 7.5 µg, or 15 µg hemagglutinin antigen of H3N2v with or without MF59 (registered trademark of Novartis AG) adjuvant (an oil-in-water emulsion). This paper reports Day 43 planned interim data.
  
  
  RESULTS
  Single MF59-adjuvanted H3N2c doses elicited immune responses in almost all subjects regardless of antigen and adjuvant dose; the Center for Biologics Evaluation Research and Review (CBER) licensure criteria were met for all groups. Subjects with prevaccination hemagglutination inhibition titers <10 and children 3-<9 years achieve CBER criteria only after receiving 2 doses of nonadjuvanted H3N2c vaccine. Highest antibody titers were observed in the 7.5 µg + 0.25 mL MF59 groups in all age cohorts. MF59-adjuvanted H3N2c vaccines showed the highest rates of solicited local and systemic events, predominately mild or moderate.
  
  
  CONCLUSIONS
  A single dose of H3N2c vaccine may be immunogenic and supports further development of MF59-adjuvanted H3N2c vaccines, especially for pediatric populations.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT01855945 (http://clinicaltrials.gov/ct2/show/NCT01855945).
authors.affiliation: Johnson County Clin-Trials LLC, Lenexa, Kansas.
authors.forename: Casey
authors.initials: C
authors.lastname: Johnson
authors.affiliation: Novartis Vaccines and Diagnostics, Inc, Cambridge, Massachusetts.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hohenboken
authors.affiliation: Heartland Research Associates LLC, Wichita, Kansas.
authors.forename: Terry
authors.initials: T
authors.lastname: Poling
authors.affiliation: Novartis Vaccines and Diagnostics, GmbH, Marburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Jaehnig
authors.affiliation: Novartis Vaccines and Diagnostics, Inc, Cambridge, Massachusetts.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Kanesa-Thasan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D018929:Cell Culture Techniques; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology* / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology* / Q000302:isolation & purification; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011136:Polysorbates / Q000008:administration & dosage / Q000009:adverse effects; D016037:Single-Blind Method; D013185:Squalene / Q000008:administration & dosage / Q000009:adverse effects; D013678:Technology, Pharmaceutical / Q000379:methods*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene
keywords: A/H3N2 variant; cell culture–derived; immunogenicity; influenza; safety; vaccine; virus