PMID- 24606983
OWN - NLM
STAT- MEDLINE
DCOM- 20150128
LR  - 20231110
IS  - 1471-2334 (Electronic)
IS  - 1471-2334 (Linking)
VI  - 14
DP  - 2014 Mar 10
TI  - A historically-controlled Phase III study in adults to characterize the 
      acceptability of a process change for manufacturing inactivated quadrivalent 
      influenza vaccine.
PG  - 133
LID - 10.1186/1471-2334-14-133 [doi]
AB  - BACKGROUND: An inactivated quadrivalent influenza vaccine (QIV) was recently 
      licenced in the US as a thimerosal-free formulation presented in a pre-filled 
      syringe. A multidose presentation is preferred in some settings due to reduced 
      acquisition and cold storage costs. We assessed the immunogenicity and safety of 
      a thimerosal-containing QIV formulated using a new manufacturing process for 
      presentation in multidose vials. METHODS: Two Phase III non-randomized studies 
      separately evaluated inactivated trivalent influenza vaccine (TIV; 2010-2011; 
      historical control) and a QIV (2011-2012). The QIV contained the same strains as 
      the TIV plus an additional B strain. Both vaccines contained thimerosal to allow 
      multidose presentation: this preservative was added to the QIV during the final 
      formulation step using a new process, whereas it was added to the TIV early in 
      the manufacturing process using an established method. The TIV study included 50 
      and 70 subjects aged 18-60 and >60 years, respectively; the QIV study included 56 
      subjects in each age stratum. Immunogenicity was assessed using 
      hemagglutination-inhibition (HI) assays. Reactogenicity was assessed during the 
      4-day post-vaccination periods and unsolicited adverse events (AEs) were assessed 
      during the 21-day post-vaccination periods. RESULTS: The TIV and QIV were 
      immunogenic in both age strata. With the QIV and TIV respectively, the 
      seroconversion rates were 48.2-62.7% and 71.4-83.7% for influenza A, and 
      33.9-62.5% and 67.3-72.9% for influenza B. With the QIV and TIV respectively, the 
      seroprotection rates were 92.9-98.2% and 98.2-100% for influenza A, and 88.6-100% 
      and 95.9-98.6% for influenza B. Pre-vaccination titers were higher in the QIV 
      versus TIV study which confounds a direct comparison and likely explains the 
      lower seroconversion rates observed in the QIV study. There were no safety 
      concerns raised with TIV or QIV. CONCLUSIONS: The thimerosal-containing QIV 
      formulated using a new process was immunogenic, conforming to regulatory 
      acceptance criteria, with a reactogenicity and safety profile in line with the 
      TIV manufactured using a licensed process. These results support acceptability of 
      a manufacturing process change in which the thimerosal preservative is added at 
      the point at which batches are filled into multidose vials. TRIAL REGISTRATION: 
      These trials were registered at ClinicalTrials.gov: NCT01440387; NCT01153685.
FAU - Jain, Varsha K
AU  - Jain VK
AD  - GlaxoSmithKline Vaccines, GCDC Non Ops, King of Prussia, PA, USA. 
      Varsha.K.Jain@gsk.com.
FAU - Chandrasekaran, Vijayalakshmi
AU  - Chandrasekaran V
FAU - Wang, Long
AU  - Wang L
FAU - Li, Ping
AU  - Li P
FAU - Liu, Aixue
AU  - Liu A
FAU - Innis, Bruce L
AU  - Innis BL
LA  - eng
SI  - ClinicalTrials.gov/NCT01153685
SI  - ClinicalTrials.gov/NCT01440387
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140310
PL  - England
TA  - BMC Infect Dis
JT  - BMC infectious diseases
JID - 100968551
RN  - 0 (Influenza Vaccines)
RN  - 2225PI3MOV (Thimerosal)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Drug Compounding
MH  - Female
MH  - Historically Controlled Study
MH  - Humans
MH  - Influenza Vaccines/*administration & dosage/adverse effects/*chemistry
MH  - Influenza, Human/immunology/*prevention & control
MH  - Male
MH  - Middle Aged
MH  - Thimerosal/administration & dosage/adverse effects/chemistry
MH  - Young Adult
PMC - PMC3995899
EDAT- 2014/03/13 06:00
MHDA- 2015/01/30 06:00
PMCR- 2014/03/10
CRDT- 2014/03/11 06:00
PHST- 2013/10/21 00:00 [received]
PHST- 2014/02/14 00:00 [accepted]
PHST- 2014/03/11 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2015/01/30 06:00 [medline]
PHST- 2014/03/10 00:00 [pmc-release]
AID - 1471-2334-14-133 [pii]
AID - 10.1186/1471-2334-14-133 [doi]
PST - epublish
SO  - BMC Infect Dis. 2014 Mar 10;14:133. doi: 10.1186/1471-2334-14-133.