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Randomized Controlled Study of the Safety and Immunogenicity of Pneumococcal Vaccine Formulations Containing PhtD and Detoxified Pneumolysin with Alum or Adjuvant System AS02(V) in Elderly Adults

Pauksens, Karlis; Nilsson, Anna LU ; Caubet, Magalie; Pascal, Thierry G.; Van Belle, Pascale; Poolman, Jan T.; Vandepapeliere, Pierre G.; Verlant, Vincent and Vink, Peter E. (2014) In Clinical and Vaccine Immunology 21(5). p.651-660
Abstract
Six vaccine formulations containing AS02(V) or alum (aluminum phosphate [AlPO4]) adjuvant with pneumococcal proteins, pneumococcal histidine triad D (PhtD), and/or detoxified pneumolysin (dPly), either as a polysaccharide carrier in an 8-valent pneumococcal conjugate vaccine (8PCV) or as free (unconjugated) proteins, were evaluated in adults -65 to 85 years of age. In this phase I observer-blind study, 167 healthy subjects were randomized to receive two doses (days 0 and 60) of 10 or 30 mu g PhtD-dPly plus AS02(V) or alum, 8PCV plus AS02(V) or alum, or one dose (day 0) of 23-valent polysaccharide pneumococcal vaccine (23PPV) as a control (placebo on day 60). The safety, reactogenicity, and antibody-specific responses to these vaccines were... (More)
Six vaccine formulations containing AS02(V) or alum (aluminum phosphate [AlPO4]) adjuvant with pneumococcal proteins, pneumococcal histidine triad D (PhtD), and/or detoxified pneumolysin (dPly), either as a polysaccharide carrier in an 8-valent pneumococcal conjugate vaccine (8PCV) or as free (unconjugated) proteins, were evaluated in adults -65 to 85 years of age. In this phase I observer-blind study, 167 healthy subjects were randomized to receive two doses (days 0 and 60) of 10 or 30 mu g PhtD-dPly plus AS02(V) or alum, 8PCV plus AS02(V) or alum, or one dose (day 0) of 23-valent polysaccharide pneumococcal vaccine (23PPV) as a control (placebo on day 60). The safety, reactogenicity, and antibody-specific responses to these vaccines were evaluated. No vaccine-related serious adverse events were reported. The incidences of solicited local and specific general (fatigue and myalgia) symptoms tended to be higher in the AS02(V) groups than in other groups. Anti-PhtD and anti-Ply antibody responses were observed in all groups except the control group. One month post-dose 2, the anti-PhtD and anti-Ply antibody geometric mean concentrations tended to be higher with AS02(V) than with alum, higher with a dose of 30 mu g than with 10 mu g for PhtD-dPly and higher with 30-mu g PhtD-dPly formulations than with conjugated PhtD and dPly (8PCV) formulations. Functional antibody responses, measured by an opsonophagocytic activity assay, tended to be higher with 8PCV than with 23PPV. In conclusion, vaccine formulations containing free or conjugated PhtD and dPly had acceptable reactogenicity and safety profiles in elderly adults. Immune responses were enhanced with an AS02(V)-adjuvanted formulation containing free 30-mu g PhtD-dPly compared to those with alum adjuvant and conjugated proteins. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical and Vaccine Immunology
volume
21
issue
5
pages
651 - 660
publisher
American Society for Microbiology
external identifiers
  • wos:000337352300007
  • scopus:84899738597
ISSN
1556-6811
DOI
10.1128/CVI.00807-13
language
English
LU publication?
yes
id
0be097b9-e928-47e7-b7f7-dca272ea345d (old id 4609735)
date added to LUP
2014-09-01 07:45:41
date last changed
2017-06-11 03:16:31
@article{0be097b9-e928-47e7-b7f7-dca272ea345d,
  abstract     = {Six vaccine formulations containing AS02(V) or alum (aluminum phosphate [AlPO4]) adjuvant with pneumococcal proteins, pneumococcal histidine triad D (PhtD), and/or detoxified pneumolysin (dPly), either as a polysaccharide carrier in an 8-valent pneumococcal conjugate vaccine (8PCV) or as free (unconjugated) proteins, were evaluated in adults -65 to 85 years of age. In this phase I observer-blind study, 167 healthy subjects were randomized to receive two doses (days 0 and 60) of 10 or 30 mu g PhtD-dPly plus AS02(V) or alum, 8PCV plus AS02(V) or alum, or one dose (day 0) of 23-valent polysaccharide pneumococcal vaccine (23PPV) as a control (placebo on day 60). The safety, reactogenicity, and antibody-specific responses to these vaccines were evaluated. No vaccine-related serious adverse events were reported. The incidences of solicited local and specific general (fatigue and myalgia) symptoms tended to be higher in the AS02(V) groups than in other groups. Anti-PhtD and anti-Ply antibody responses were observed in all groups except the control group. One month post-dose 2, the anti-PhtD and anti-Ply antibody geometric mean concentrations tended to be higher with AS02(V) than with alum, higher with a dose of 30 mu g than with 10 mu g for PhtD-dPly and higher with 30-mu g PhtD-dPly formulations than with conjugated PhtD and dPly (8PCV) formulations. Functional antibody responses, measured by an opsonophagocytic activity assay, tended to be higher with 8PCV than with 23PPV. In conclusion, vaccine formulations containing free or conjugated PhtD and dPly had acceptable reactogenicity and safety profiles in elderly adults. Immune responses were enhanced with an AS02(V)-adjuvanted formulation containing free 30-mu g PhtD-dPly compared to those with alum adjuvant and conjugated proteins.},
  author       = {Pauksens, Karlis and Nilsson, Anna and Caubet, Magalie and Pascal, Thierry G. and Van Belle, Pascale and Poolman, Jan T. and Vandepapeliere, Pierre G. and Verlant, Vincent and Vink, Peter E.},
  issn         = {1556-6811},
  language     = {eng},
  number       = {5},
  pages        = {651--660},
  publisher    = {American Society for Microbiology},
  series       = {Clinical and Vaccine Immunology},
  title        = {Randomized Controlled Study of the Safety and Immunogenicity of Pneumococcal Vaccine Formulations Containing PhtD and Detoxified Pneumolysin with Alum or Adjuvant System AS02(V) in Elderly Adults},
  url          = {http://dx.doi.org/10.1128/CVI.00807-13},
  volume       = {21},
  year         = {2014},
}