title: Phase I, randomized, observer-blind, placebo-controlled studies to evaluate the safety, reactogenicity and immunogenicity of an investigational non-typeable Haemophilus influenzae (NTHi) protein vaccine in adults.
abstract: Non-typeable Haemophilus influenzae (NTHi) is a major cause of various respiratory diseases. The development of an effective vaccine against NTHi mandates new approaches beyond conjugated vaccines as this opportunistic bacterium is non-encapsulated. Here we report on the safety, reactogenicity and immunogenicity of a multi-component investigational vaccine based on three conserved surface proteins from NTHi (proteins D [PD], E [PE] and Pilin A [PilA]) in two observer-blind phase I studies.
  
  
  
  In the first study (NCT01657526), 48 healthy 18-40 year-olds received two vaccine formulations (10 or 30μg of each antigen [PD and a fusion protein PE-PilA]) or saline placebo at months 0 and 2. In the second study (NCT01678677), 270 50-70 year-olds, current or former smokers, received eight vaccine formulations (10 or 30μg antigen/dose non-adjuvanted or adjuvanted with alum, AS01E or AS04C) or saline placebo at months 0, 2 and 6 (plain and alum-adjuvanted groups) and at months 0 and 2 (AS-adjuvanted groups). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post-vaccination, respectively; potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) throughout the studies. Humoral and antigen-specific T-cell immunity (in study 2 only) responses were assessed up to 12 months post-vaccination.
  
  
  
  Observed reactogenicity was highest in the AS-adjuvanted groups but no safety concerns were identified with any of the NTHi vaccine formulations. One fatal SAE (cardiac arrest) not considered related to vaccination, and one pIMD (non-serious psoriasis) in the Placebo group, were reported post-dose 3 in Study 2. All formulations generated a robust antibody response while the AS01-adjuvanted formulations produced the highest humoral and cellular immune responses.
  
  
  
  This study confirms that the NTHi vaccine formulations had an acceptable reactogenicity and safety profile and were immunogenic in adults. These results justify further clinical development of this NTHi vaccine candidate.
authors.affiliation: Center for Vaccinology, Ghent University and Ghent University Hospital, BC001, De Pintelaan 185, B-9000 Ghent, Belgium. Electronic address: Geert.LerouxRoels@UGent.be.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.affiliation: Centre for the Evaluation of Vaccination, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Antwerp, Belgium. Electronic address: pierre.vandamme@uantwerpen.be.
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Damme
authors.affiliation: SGS Life Sciences Services, Lange Beeldekensstraat 267, 2060 Antwerp, Belgium. Electronic address: wouter.haazen1@telenet.be.
authors.forename: Wouter
authors.initials: W
authors.lastname: Haazen
authors.affiliation: University of Adelaide, Mail Delivery Point 22, Royal Adelaide Hospital, North Terrace, 5000 Adelaide, Australia. Electronic address: sepehr.shakib@sa.gov.au.
authors.forename: Sepehr
authors.initials: S
authors.lastname: Shakib
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: magalie.caubet@gsk.com.
authors.forename: Magalie
authors.initials: M
authors.lastname: Caubet
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: emmanuel.x.aris@gsk.com.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Aris
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: jeanne-marie.devaster@gsk.com.
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Devaster
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: Mathieu.peeters@yahoo.co.uk.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Peeters
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D001315:Australia; D001530:Belgium; D005260:Female; D006192:Haemophilus Infections / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000276:immunology / Q000627:therapeutic use*; D006193:Haemophilus influenzae; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D018074:Vaccines, Conjugate; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D018073:Haemophilus Vaccines; D018074:Vaccines, Conjugate
keywords: Adjuvant; Adult vaccination; Immunogenicity; NTHi; Safety