title: Stable emulsion (SE) alone is an effective adjuvant for a recombinant, baculovirus-expressed H5 influenza vaccine in healthy adults: A Phase 2 trial.
abstract: Influenza A viruses of the H5 subtype have been identified as important targets for development of vaccines. Achievement of potentially protective antibody responses against pandemic strains has usually required the use of adjuvants.
  
  
  
  We evaluated a candidate A/Indonesia/05/2005 (H5) vaccine generated by baculovirus expression of recombinant hemagglutinin (HA) protein with or without stable emulsion (SE) as an adjuvant.
  
  
  
  Healthy subjects 18-49years old were randomized (1:1:1:1) to receive two doses of rHA at 7.5ug per dose (no adjuvant), or 3.8ug, 7.5ug, or 15ug per dose formulated with 2% SE separated by 21days, and serum from day 0, 21, 42, and 201 assessed by hemagglutination-inhibition.
  
  
  
  341 subjects were enrolled in the study and 321 received two doses of vaccine. Vaccination was well tolerated in all groups. After two doses, seroconversion was noted in only 9% (95% confidence interval 4%, 17%) of recipients of unadjuvanted vaccine at 7.5ug, but in 70% (59%, 80%), 76% (65%, 85%), and 83% (73%, 91%) of those receiving adjuvanted vaccine at 3.8ug, 7.5ug, or 15ug respectively.
  
  
  
  Stable emulsion alone is an effective adjuvant for rH5 vaccine in healthy adults. All three adjuvanted dose groups met the current criterion for seroconversion rate for pandemic vaccines. This dose-ranging study also identified a group (15ug per dose formulated with 2% SE) that met the criteria for both seroconversion and percentage of subjects achieving an HI antibody titer⩾40. These Phase 2 data support the further clinical development of SE adjuvanted Panblok H5.
  
  
  
  NCT01612000. The protocol was approved by the relevant Institutional Review Board for each study site, and the study was conducted in accordance with the Declaration of Helsinki, International Conference of Harmonisation - Good Clinical Practice, and all applicable laws and regulations. All participants provided written informed consent before study procedures.
authors.affiliation: University of Rochester Medical Center, Rochester, NY, United States. Electronic address: John_Treanor@UMRC.Rochester.edu.
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.affiliation: Benchmark Research, Austin, TX, United States.
authors.forename: Laurence
authors.initials: L
authors.lastname: Chu
authors.affiliation: Meridian Clinical Research, Omaha, NE, United States.
authors.forename: Brandon
authors.initials: B
authors.lastname: Essink
authors.affiliation: Jean Brown Research, Salt Lake City, UT, United States.
authors.forename: Derek
authors.initials: D
authors.lastname: Muse
authors.affiliation: Baylor College of Medicine, Houston, TX, United States.
authors.forename: Hana M
authors.initials: HM
authors.lastname: El Sahly
authors.affiliation: Protein Sciences Corporation, Meriden, CT, United States.
authors.forename: Ruvim
authors.initials: R
authors.lastname: Izikson
authors.affiliation: Independent Consultant, Bethesda, MD, United States.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Goldenthal
authors.affiliation: Biologics Consulting Group, Bethesda, MD, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Patriarca
authors.affiliation: Protein Sciences Corporation, Meriden, CT, United States.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Dunkle
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis*; D016367:Baculoviridae / Q000235:genetics / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004655:Emulsions; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D014614:Vaccines, Synthetic
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004655:Emulsions; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic
keywords: Adjuvant; Influenza; Pandemic; Recombinant HA; Vaccine