A historically-controlled Phase III study in adults to characterize the acceptability of a process change for manufacturing inactivated quadrivalent influenza vaccine

BMC Infectious Diseases

Bruce L Innis¹  Aixue Liu¹  Ping Li¹  Long Wang¹  Vijayalakshmi Chandrasekaran¹  Varsha K Jain¹ 

[1] GlaxoSmithKline Vaccines, GCDC Non Ops, King of Prussia, PA, USA

关键词: Adults;    Influenza;    Inactivated;    Trivalent;    Quadrivalent;    Thimerosal-containing;   

Others  :  1134381
DOI  :  10.1186/1471-2334-14-133

 received in 2013-10-21, accepted in 2014-02-14,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Jain et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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