Systematic review of the efficacy, effectiveness and safety of cell‐based seasonal influenza vaccines for the prevention of laboratory‐confirmed influenza in individuals ≥18 years of age

Abstract

The most effective means of preventing seasonal influenza is through strain‐specific vaccination. In this study, we investigated the efficacy, effectiveness and safety of cell‐based trivalent and quadrivalent influenza vaccines. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non‐randomised studies of interventions (NRSIs) were eligible for inclusion. Two reviewers independently screened, extracted data and assessed the risk of bias of included studies. Certainty of evidence for key outcomes was assessed using the GRADE methodology. The search returned 28,846 records, of which 868 full‐text articles were assessed for relevance. Of these, 19 studies met the inclusion criteria. No relative efficacy data were identified for the direct comparison of cell‐based vaccines compared with traditional vaccines (egg‐based). Efficacy data were available comparing cell‐based trivalent influenza vaccines with placebo in adults (aged 18–49 years). Overall vaccine efficacy was 70% against any influenza subtype (95% CI 61%–77%, two RCTS), 82% against influenza A(H1N1) (95% CI 71%–89%, 2 RCTs), 72% against influenza A(H3N2) (95% CI 39%–87%, 2 RCTs) and 52% against influenza B (95% CI 30%–68%, 2 RCTs). Limited and heterogeneous data were presented for effectiveness when compared with no vaccination. One NRSI compared cell‐based trivalent and quadrivalent vaccination with traditional trivalent and quadrivalent vaccination, finding a small but significant difference in favour of cell‐based vaccines for influenza‐related hospitalisation, hospital encounters and physician office visits. The safety profile of cell‐based trivalent vaccines was comparable to traditional trivalent influenza vaccines. Compared with placebo, cell‐based trivalent influenza vaccines have demonstrated greater efficacy in adults aged 18–49 years. Overall cell‐based vaccines are well‐tolerated in adults, however, evidence regarding the effectiveness of these vaccines compared with traditional seasonal influenza vaccines is limited.

Estimates of Seasonal Influenza Burden That Could Be Averted by Improved Influenza Vaccines in the Australian Population Aged Under 65 Years, 2015–2019

“…Vaccination is the primary strategy to reduce influenza transmission and disease burden [4][5][6]. Standard inactivated egg-based vaccines are manufactured by combining the haemagglutinin (HA) and neuraminidase (NA) genes from selected variants with genes from viruses designed to grow well in eggs [7].…”

“…Adjuvanted egg-based vaccines include an adjuvant that enhances the immune response to the vaccine antigen [5]. Cell-based vaccines propagate vaccine viruses in cell culture to avoid the risk of egg adaptations that alter antigenicity and compromise vaccine effectiveness (VE) [6]. Recombinant vaccines similarly avoid problems of egg adaptation by using a recombinant technology to produce purified HA from a baculovirus overexpression system.…”

“…Table S2. Estimated absolute vaccine effectiveness (aVE) and difference in aVE of an improved influenza vaccine under a range of relative vaccine effectiveness assumptions using FluCAN estimates of standard influenza vaccine effectiveness [4–9]. Table S3.…”

Systematic review of the efficacy, effectiveness and safety of high‐dose seasonal influenza vaccines for the prevention of laboratory‐confirmed influenza in individuals ≥18 years of age

“…9,12 A series of systematic reviews was undertaken to investigate the efficacy, effectiveness and safety of newer and enhanced influenza vaccines for the prevention of laboratory-confirmed influenza in individuals aged 18 years or older. 13,14 The aim of this current review was to determine the efficacy (i.e., how well a vaccine performs in the context of a controlled trial), effectiveness (i.e., how well a vaccine performs in real world settings) and safety of high-dose trivalent (HD-IIV3) and quadrivalent (HD-IIV4) egg-based seasonal influenza vaccines by influenza type, subtype, age and risk group.…”

Challenges encountered during the systematic review of newer and enhanced influenza vaccines and recommendations for the future

“…A range of influenza vaccines are available that can, if well matched to the circulating strains, substantially reduce the burden of mortality. In response to a call from the European Centre for Disease Prevention and Control (ECDC), a series of systematic reviews were carried out to assess and synthesise the literature on the efficacy, effectiveness and safety of newer and enhanced inactivated seasonal influenza vaccines for the prevention of laboratory‐confirmed influenza in individuals aged 18 years or older 2‐5 …”