title: First-in-human safety and immunogenicity investigations of three adjuvanted reduced dose inactivated poliovirus vaccines (IPV-Al SSI) compared to full dose IPV Vaccine SSI when given as a booster vaccination to adolescents with a history of IPV vaccination at 3, 5, 12months and 5years of age.
abstract: There is a demand of affordable IPV in the World. Statens Serum Institut (SSI) has developed three reduced dose IPV formulations adsorbed to aluminium hydroxide; 1/3 IPV-Al, 1/5 IPV-Al and 1/10 IPV-Al SSI, and now report the results of the first investigations in humans.
  
  
  
  240 Danish adolescents, aged 10-15years, and childhood vaccinated with IPV were booster vaccinated with 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al or IPV Vaccine SSI. The booster effects (GMTRs) of the three IPV-Al SSI were compared to IPV Vaccine SSI, and evaluated for non-inferiority.
  
  
  
  The pre-vaccination GMTs were similar across the groups; 926 (type 1), 969 (type 2) and 846 (type 3) in the total trial population. The GMTRs by poliovirus type and IPV formulation were: Type 1: 17.0 (1/3 IPV-Al), 13.0 (1/5 IPV-Al), 7.1 (1/10 IPV-Al) and 42.2 (IPV Vaccine SSI). Type 2: 12.5 (1/3 IPV-Al), 13.1 (1/5 IPV-Al), 7.6 (1/10 IPV-Al) and 47.8 (IPV Vaccine SSI). Type 3: 14.5 (1/3 IPV-Al), 16.2 (1/5 IPV-Al), 8.9 (1/10 IPV-Al) and 62.4 (IPV Vaccine SSI) Thus, the three IPV-Al formulations were highly immunogenic, but inferior to IPV Vaccine SSI, in this booster vaccination trial.
  
  
  
  No SAE and no AE of severe intensity occurred. 59.2% of the subjects reported at least one AE. Injection site pain was the most frequent AE in all groups; from 24.6% to 43.3%. Injection site redness and swelling frequencies were<5% in most and<10% in all groups. The most frequent systemic AEs were fatigue (from 8.2% to 15.0%) and headache (from 15.0% to 28.3%). Most AEs were of mild intensity. In conclusion, the three IPV-Al SSI were safe in adolescents and the booster effects were satisfactory. ClinicalTrials.gov registration number: NCT02280447.
authors.affiliation: Center for Clinical and Basic Research (CCBR), Ballerup Byvej 222, 2750 Ballerup, Denmark.
authors.forename: Line M
authors.initials: LM
authors.lastname: Lindgren
authors.affiliation: Statens Serum Institut, 5 Artillerivej, 2300 Copenhagen S., Denmark.
authors.forename: Pernille N
authors.initials: PN
authors.lastname: Tingskov
authors.affiliation: CCBR Vejle, Orla Lehmannsgade 1(3), 7100 Vejle, Denmark.
authors.forename: Annette H
authors.initials: AH
authors.lastname: Justesen
authors.affiliation: CCBR Aalborg, Hobrovej 42 D(2), 9000 Aalborg, Denmark.
authors.forename: Bettina S
authors.initials: BS
authors.lastname: Nedergaard
authors.affiliation: Larix A/S, Lyskær 8b, 2730 Herlev, Denmark.
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Olsen
authors.affiliation: Statens Serum Institut, 5 Artillerivej, 2300 Copenhagen S., Denmark.
authors.forename: Lars V
authors.initials: LV
authors.lastname: Andreasen
authors.affiliation: Statens Serum Institut, 5 Artillerivej, 2300 Copenhagen S., Denmark.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kromann
authors.affiliation: Statens Serum Institut, 5 Artillerivej, 2300 Copenhagen S., Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Sørensen
authors.affiliation: Statens Serum Institut, 5 Artillerivej, 2300 Copenhagen S., Denmark.
authors.forename: Jes
authors.initials: J
authors.lastname: Dietrich
authors.affiliation: Statens Serum Institut, 5 Artillerivej, 2300 Copenhagen S., Denmark. Electronic address: btc@ssi.dk.
authors.forename: Birgit
authors.initials: B
authors.lastname: Thierry-Carstensen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003718:Denmark; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D007223:Infant; D008297:Male; D011051:Poliomyelitis / Q000517:prevention & control*; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D011054:Poliovirus Vaccine, Inactivated; D000536:Aluminum Hydroxide
keywords: Affordable IPV; Aluminium hydroxide adjuvant; Dose investigation; IPV dose sparing