Immunogenicity and safety of a quadrivalent influenza vaccine in children and adolescents in Taiwan: A phase III open-label trial

Until recently, all seasonal influenza vaccines have been trivalent, containing strains A(H1N1), A(H3N2), and one of the two B strain lineages (Yamagata or Victoria), resulting in frequent mismatches between the circulating B strain lineage and that included in the vaccine. A quadrivalent, inactivated, split-virion influenza vaccine (IIV4) containing strains from both B lineages has been developed to address this. We performed an open-label phase III study to assess the immunogenicity and safety of the 2013-2014 Northern Hemisphere formulation of IIV4 in children and adolescents 9-17 years of age in Taiwan. Participants were vaccinated with one dose of IIV4 by intramuscular or deep subcutaneous injection. Hemagglutinin inhibition (HAI) titers were measured before and 21 days after vaccination. Solicited injection-site and systemic reactions were assessed for up to 7 days after vaccination, and adverse events (AEs) were recorded until day 21. One hundred participants were included. Despite relatively high pre-vaccination titers, post-vaccination HAI titers increased for all four strains, with geometric mean ratios (day 21/day 0) of 2.29 for A(H1N1), 2.05 for A(H3N2), 3.33 for B/Massachusetts (Yamagata lineage), and 4.59 for B/Brisbane (Victoria lineage). Post-vaccination seroprotection rates were 99% for A(H3N2) and 100% for A(H1N1), B/Massachusetts, and B/Brisbane. Due to high pre-vaccination titers, rates of seroconversion/significant increase of HAI titer were relatively low at 24% for A(H1N1), 20% for A(H3N2), 39% for B/Massachusetts, and 48% for B/Brisbane. Injection-site pain (56%), myalgia (45%), and malaise (15%) were the most frequently reported solicited reactions, and most solicited reactions were mild or moderate. No treatment-related AEs, immediate unsolicited AEs, unsolicited non-serious injection-site AEs, grade 3 unsolicited AEs, or serious AEs were reported. In conclusion, this study showed that the 2013-2014 Northern Hemisphere formulation of the intramuscular IIV4 was immunogenic and well tolerated by children and adolescents 9-17 years of age.