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
Highlights
Two 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
Trivalent influenza vaccines recommended for immunization against influenza contain the two A-strains (H1N1 and H3N2) but only one B-strain selected each year in the Yamagata-like lineage group or the Victorialike one [9,29]
The addition of a fourth strain in the quadrivalent influenza vaccine (QIV) vaccine formulations did not impact the immune response elicited in healthy adults aged 18 to 60 years to the three strains contained in the trivalent influenza vaccine (TIV) vaccines, as demonstrated by the statistical noninferiority of the immunological response elicited by QIV and LD QIV-AS over TIV and LD TIV-AS 21 days after vaccination
Summary
Two 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. The influenza viruses in circulation in the human population are A(H1N1), A (H3N2) and two distinct lineages of B-strain: the B/ Victoria/2/87 and B/Yamagata/16/88 lineages [2]. These have coexisted since 1983 in the human population [3], and both strains have circulated broadly worldwide since 1988 [1,2,4,5]. From 1976 to 1999, 16% of the influenza-associated deaths in the US were caused by influenza B and occurred mostly in the elderly population, they represent 46% of all influenza related death in children below the age of 5 years [8]
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