Immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine: a Phase III, open-label study of adults in Brazil

Abstract The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines.In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18–60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed.A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults.The study showed that inactivated quadrivalent influenza vaccine was immunogenic and well-tolerated in Brazilian adults and older adults.

Immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine: a Phase III, open-label study of adults in Brazil.

The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines. In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18-60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed. A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults. The study showed that inactivated quadrivalent influenza vaccine was immunogenic and well-tolerated in Brazilian adults and older adults.

Immunogenicity and Reactogenicity of an Inactivated Quadrivalent Influenza Vaccine Administered Intramuscularly to Children 6 to 35 Months of Age in 2012-2013: A Randomized, Double-Blind, Controlled, Multicenter, Multicountry, Clinical Trial.

BACKGROUND: Influenza attack rates are high in 6- to 35-month-old children; vaccines containing both lineages of influenza B (Yamagata and Victoria), in addition to the H3N2 and H1N1 antigens, may improve protection rates. METHODS: In a randomized double-blind controlled trial, the immunogenicity and reactogenicity of an inactivated quadrivalent influenza vaccine (QIV) and a trivalent control vaccine (TIV) were assessed. RESULTS: Six hundred one children (QIV, n = 299; TIV, n = 302) were enrolled at 8 sites in 3 countries. The primary immunogenicity objective was met: the lower limit (LL) of the 2-sided 95% confidence interval (CI) for the seroconversion rate in QIV recipients ranged from 66.6% to 81.3%, which was ≥40% against all 4 strains. The immunogenic superiority of the additional B/Victoria strain in the QIV compared to that in the TIV was confirmed: the LL of the 2-sided 95% CI of the geometric mean titer ratio (QIV/TIV) (6.28 [95% CI, 5.32-7.41]) was greater than 1.5, and the LL of the 2-sided 95% CI for the difference in the seroconversion rate (QIV - TIV) (64.19% [95% CI, 57.65%-69.95%]) was greater than 10%. Injection-site pain and irritability/fussiness were the most commonly reported solicited injection-site and general adverse events, respectively, from days 0 to 6 and were similar in frequency between the groups. CONCLUSIONS: In children aged 6 to 35 months, a QIV has superior immunogenicity for the added B strain and acceptable immunogenicity for shared strains, with no notable difference in reactogenicity and safety when compared to a TIV.

Immunogenicity and safety of inactivated quadrivalent and trivalent influenza vaccines in children 18-47 months of age.

BACKGROUND: Because inactivated trivalent influenza vaccines (TIVs) contain 1 influenza B strain, whereas 2 lineages may co-circulate, B lineage mismatch is frequent. We assessed an inactivated quadrivalent influenza vaccine (QIV) containing both B lineages versus TIV in young children. METHODS: Children aged 18-47 months who had received 2 doses of TIV in a study during the previous season (primed cohort, n = 192) were randomized 1:1 to receive 1 dose of TIV or QIV, and a further 407 children (unprimed cohort) were randomized 1:1 to receive 2 doses of TIV or QIV 28 days apart. Immunogenicity was assessed by hemagglutination-inhibition (HI) prevaccination and 28 days after each vaccination. Immunogenic non-inferiority QIV versus TIV for shared strains, and superiority against the alternate-lineage B strain were based on HI geometric mean titers (pooled analyses of primed and half of unprimed cohort with Day 56 immunogenicity assessment). Solicited and unsolicited adverse events were assessed during each 7- and 28-day postvaccination period, respectively (NCT00985790). RESULTS: Non-inferiority for shared strains and superiority for the alternate-lineage B strain unique to QIV was demonstrated for QIV versus TIV. QIV was immunogenic against all 4 vaccine strains and 87.0%, 88.6%, 69.8% and 97.9% of children had postvaccination titers of ≥ 1:40 against A/H1N1, A/H3N2, B/Victoria and B/Yamagata, respectively. Reactogenicity and safety of QIV was consistent with TIV. CONCLUSIONS: QIV provided superior immunogenicity for the alternate-lineage B strain compared with TIV without interfering with immune responses to shared strains. Further studies are warranted to assess QIVs in children and to establish the clinical benefits of QIV versus TIV.