Compared with the standard-dose influenza vaccine, a high-dose quadrivalent inactivated influenza vaccine, GC3114, may provide more effective influenza prevention for the elderly population and has been shown to be safe, well tolerated, and immunogenic in healthy adults, according to a study published in Vaccine.
With between 291,243 and 645,832 seasonal influenza-associated respiratory mortalities occurring annually, influenza represents one of the major public health concerns. Influenza-associated mortality is higher in the elderly than in younger individuals, and the study authors noted that all-cause mortality rate associated with influenza is 46.98 per 100,000 in the elderly (age ≥65 years) and 5.97 per 100,000 in people of all ages in the Republic of Korea. The primary strategy to reduce the burden of influenza-associated disease is vaccination.
However, immunosenescence in the elderly increases vulnerability for influenza and related complications and attenuates the immunogenicity of influenza vaccine. Therefore, a strategy is needed to improve the immunogenicity of the influenza vaccine in the elderly. Although a high-dose trivalent inactivated vaccine was approved in the United States for use in the elderly and demonstrated improved protection, influenza B virus accounts for approximately 25% of all cases of influenza infection. This highlights the need for a quadrivalent influenza vaccine for cross-protection, especially in high-risk individuals like the elderly. Therefore, this phase 1 clinical trial investigated the immunogenicity and safety of GC3114, high-dose quadrivalent inactivated influenza vaccine in healthy adults during the 2017 through 2018 season (ClinicalTrials.gov identifier: NCT03357263).
In total, 40 participants aged between 19 years and 64 years who had not been vaccinated for influenza within the previous 6 months from the Republic of Korea were included in the study. These participants were randomly assigned to receive the high-dose quadrivalent GC3114 vaccine (n=30) or the standard-dose GC FLU quadrivalent vaccine (n=10). Blood samples were collected before vaccination and then participants received a single dose (0.5 mL) of their assigned vaccine intramuscularly to the deltoid muscle. The primary outcome of the study was safety of GC3114 and the secondary outcome of the study was immunogenicity of GC3114. Safety was assessed for 21 days postvaccination by means of solicited adverse events for 7 days and unsolicited adverse events for 21 days. Immunogenicity was measured for 21 days after vaccination.
Results showed that the G3114 vaccine was safe, well tolerated, and immunogeneic in healthy adults. The reactogenicity of high-dose quadrivalent vaccine was not significantly different from that of the standard-dose vaccine in this study. Between the 2 groups, the frequency of adverse events was similar. In the high-dose group, there were 2 adverse events of grade 3 that were determined to be related to the vaccine, while the adverse events related to the vaccine in the standard-dose quadrivalent vaccine group were grade 2 or below. There were no unsolicited adverse events or serious adverse events reported in this study.
Seroprotection rates for the high-dose group were 100% for A/H1N1, 96.67% for A/H3N2, 83.33% for B/Yamagata, and 96.67% for B/Victoria. The seroprotection rates were higher in the high-dose group compared with the standard-dose group for B/Yamagata, but this was not a significant difference. The seroconversion rates for the high-dose group were 86.67% for A/H1N1, 90.0% for A/H3N2, 53.33% for B/Yamagata, and 53.33% for B/Victoria. The seroconversion rates were higher in the high-dose group compared with the standard-dose group for A/H1N1 (P =.03), A/H3N2 (P <.01), B/Yamagata (P =.08), and B/Victoria (P =.28). In addition, the postvaccination/prevaccination geometric mean titer ratio for A/H2N2 was significantly higher in the higher-dose group compared with the standard-dose group (P <.01).
Overall, the study authors concluded that, “Further confirmatory studies on the safety and immunogenicity of GC3114 [are] required in adults aged 65 years and older.”
Noh JY, Jang YS, Lee SN, et al. Randomized, single-blind, active-controlled phase I clinical trial to evaluate the immunogenicity and safety of GC3114 (high-dose, quadrivalent influenza vaccine) in healthy adults. Vaccine. 2019;37:5171-5176.