Immunogenicity and safety of quadrivalent versus trivalent inactivated influenza vaccine: a randomized, controlled trial in adults

Abstract

BackgroundTwo phylogenetic lineages of influenza B virus coexist and circulate in the human population (B/Yamagata and B/Victoria) but only one B-strain is included in each seasonal vaccine. Mismatch regularly occurs between the recommended and circulating B-strain. Inclusion of both lineages in vaccines may offer better protection against influenza.MethodsThis study (NCT00714285) assessed the immunogenicity and safety of two candidate quadrivalent influenza vaccines (QIV) containing two A- and two B-strains (one from each lineage) in adults (18–60 years). Subjects were randomized and stratified by age to receive either QIV (non-adjuvanted or low-dose adjuvanted [LD QIV-AS]) or trivalent influenza vaccine (TIV, non-adjuvanted or low-dose adjuvanted [LD TIV-AS]), N = 105 in all treatment groups. The study evaluated the statistical non-inferiority of the immunological response elicited by QIV and LD QIV-AS versus TIV and LD TIV-AS and the statistical superiority of the response elicited by the quadrivalent vaccines against the B-strain (B/Jiangsu) not included in the TIV.ResultsPre-defined non-inferiority and superiority criteria were reached for both QIVs compared to the TIVs. On Day 21 in all vaccine groups SCRs were ≥54.8%, SPRs ≥88.5% and SCFs ≥5.4 for the A strains and B strain included in all vaccines (B/Malaysia). This fulfilled the European (CHMP) and the US (CBER) licensing criteria for the assessment of influenza vaccines in adults (CHMP criteria: SCR > 40%, SPR > 70%, SCF > 2; CBER criteria: LL of 95% CI for SPR ≥ 70% or SCR ≥ 40%). Only the QIVs met the CHMP and CBER criteria for the B/Jiangsu strain. In the QIV and LD-QIV-AS groups, the SCFs were 9.1 and 8.1, respectively and the SPRs were 98.1% and 95.2%, whereas for the TIV and LD-TIV-AS groups, the SCFs were 2.3 and 2.5, respectively, and the SPRs were 75.0% and 63.8%, with the LLs of the 95% CI <70% for SPR and <40% for SCR.ConclusionsAddition of a fourth strain did not impact the immune response elicited by the three original strains contained in the TIV. A clear immunological benefit was seen with the QIV formulation for the second B-strain, indicating that quadrivalent vaccines could provide broader protection against influenza.Trial registrationClinicalTrials.gov: NCT00714285

Prevention and Control of Seasonal Influenza with Vaccines

“…Among adults the most common safety complaints were injection-site pain and systemic reactions, such as myalgia, headaches, and fatigue (123,125,127,129,130,309). The first postlicensure safety assessment of VAERS reports covering the 2013-14 and 2014-15 seasons noted a safety profile similar to that of IIV3.…”

Evaluating the case for trivalent or quadrivalent influenza vaccines

“…There were no differences between the trivalent and quadrivalent preparations with regard to safety and reactogenicity. [36][37][38][39][40][41] There is an increased cost associated with the use of quadrivalent vaccines but modeling studies suggest a significant societal cost saving even if the cost is significantly higher than the trivalent preparation. [42][43][44] …”

Fluarix quadrivalent vaccine for influenza

“…All studies were funded by the manufacturer (GSK). A summary on the findings is shown in [20]. One hundred and four participants were included in each group and the results showed that predefined non-inferiority criteria were reached for both QIVs compared to the TIVs for the three strains in the TIV.…”