title: Adjuvant system AS02V enhances humoral and cellular immune responses to pneumococcal protein PhtD vaccine in healthy young and older adults: randomised, controlled trials.
abstract: BACKGROUND
  The protection elicited by polysaccharide pneumococcal vaccines against community-acquired pneumonia in older adults remains debatable. Alternative vaccine targets include well-conserved pneumococcal protein antigens, such as pneumococcal histidine triad protein D (PhtD).
  
  
  OBJECTIVE
  To evaluate humoral and cellular immune responses and safety/reactogenicity following immunisation with PhtD vaccine with or without adjuvant (alum or AS02V) in older (≥65 years) and young (18-45 years) healthy adults.
  
  
  METHODS
  Two phase I/II, single-blind, parallel-group studies were conducted in 150 older and 147 young adults. Participants were randomised to receive 2 doses (months 0 and 2) of PhtD 30 μg, PhtD 10 μg plus alum, PhtD 30 μg plus alum, PhtD 10 μg plus AS02V or PhtD 30 μg plus AS02V, or the 23-valent polysaccharide pneumococcal vaccine (23PPV) at month 0 with placebo (saline solution) at month 2. Safety/reactogenicity was assessed. PhtD-specific antibody, T cell and memory B cell responses were evaluated.
  
  
  RESULTS
  Solicited adverse events were more common in young participants and with adjuvanted vaccines. No vaccine-related serious adverse events were reported. Although anti-PhtD geometric mean antibody concentrations (GMCs) were consistently lower in the older adult cohort than in young adults, GMCs in the older cohort following PhtD 30 μg plus AS02V were comparable to those induced by plain PhtD or PhtD 30 μg plus alum in the young cohort. Compared with alum adjuvant, AS02V adjuvant system was associated with an increased frequency of PhtD-specific CD4 cells in both cohorts and a significantly higher specific memory B cell response in the older cohort, similar to responses obtained in the young cohort.
  
  
  CONCLUSIONS
  The improved immune response to PhtD vaccine containing the AS02V adjuvant system in comparison to alum suggests that the reduced immune response to vaccines in older adults can be partially restored to the response level observed in young adults. ClinicalTrials.gov identifiers: NCT00307528/NCT01767402.
authors.affiliation: Centre for Vaccinology, Ghent University and Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: isabel.lerouxroels@ugent.be.
authors.forename: Isabel
authors.initials: I
authors.lastname: Leroux-Roels
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium. Electronic address: jeanne-marie.devaster@gsk.com.
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Devaster
authors.affiliation: Centre for Vaccinology, Ghent University and Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: geert.lerouxroels@ugent.be.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium. Electronic address: vincent.verlant@gsk.com.
authors.forename: Vincent
authors.initials: V
authors.lastname: Verlant
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium. Electronic address: isabelle.henckaerts@gsk.com.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Henckaerts
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium. Electronic address: philippe.moris@gsk.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium. Electronic address: philippe.hermand@gsk.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hermand
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium. Electronic address: pascale.van-belle@gsk.com.
authors.forename: Pascale
authors.initials: P
authors.lastname: Van Belle
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium; Crucell, PO Box 2048, 2301 CA, Leiden, The Netherlands. Electronic address: jan.poolman@crucell.com.
authors.forename: Jan T
authors.initials: JT
authors.lastname: Poolman
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium; Neovacs S.A., 3-5, Impasse Reille, 75014 Paris, France. Electronic address: pierre.vandepapeliere@hotmail.com.
authors.forename: Pierre
authors.initials: P
authors.lastname: Vandepapelière
authors.affiliation: Unité de Pharmacologie Clinique, University Hospital St-Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium. Electronic address: yves.horsmans@uclouvain.be.
authors.forename: Yves
authors.initials: Y
authors.lastname: Horsmans
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016037:Single-Blind Method; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D010919:Placebos; D022242:Pneumococcal Vaccines
keywords: Adjuvant; Immunosenescence; PhtD; Pneumonia; Streptococcus pneumoniae; Vaccine