Immunogenicity and safety of high-dose quadrivalent influenza vaccine in Japanese adults ≥65 years of age: a randomized controlled clinical trial

Leilani Sanchez,Osamu Matsuoka,Satoshi Inoue,Takahiro Inoue,Ya Meng,Takahiro Nakama,Kumiko Kato,Aseem Pandey,Lee-Jah Chang

doi:10.1080/21645515.2019.1677437

Abstract

ABSTRACT A trivalent high-dose inactivated influenza vaccine has been licensed in healthy adults ≥65 years of age and provides better protection against influenza infection and related complications than trivalent standard-dose vaccine. This phase I/II clinical trial (NCT03233217), conducted at two sites in Japan, examined the safety and immunogenicity of a quadrivalent formulation of the high-dose inactivated influenza vaccine (IIV4-HD). Healthy adults ≥65 years of age were randomized to receive IIV4-HD by intramuscular injection (n = 60), IIV4-HD by subcutaneous injection (n = 60), or a quadrivalent standard-dose inactivated influenza vaccine (IIV4-SD) by subcutaneous injection (n = 55). Irrespective of administration route, post-vaccination (day 28–35) hemagglutination inhibition geometric mean titers and seroconversion rates were higher for IIV4-HD than for IIV4-SD. Hemagglutination inhibition geometric mean titers and seroconversion rates were also higher for intramuscular than subcutaneous administration of IIV4-HD. Solicited reactions were more common in participants who received IIV4-HD administered subcutaneously than in those who received IIV4-HD administered intramuscularly or IIV4-SD administered subcutaneously. Unsolicited adverse events were similar between the vaccine groups, and no safety signals were detected. This study showed that IIV4-HD administered by either intramuscular or subcutaneous injection was well tolerated and highly immunogenic in healthy Japanese adults ≥65 years of age. Although this study was descriptive, the results add to the evidence that high-dose inactivated influenza vaccines are more immunogenic than standard-dose vaccines in this age group and that intramuscular administration provides greater immunogenicity and lower reactogenicity than subcutaneous administration.

Highlights

Most influenza-related hospitalizations and deaths occur in adults ≥65 years of age.[1]
All participants were vaccinated as randomized and completed the study according to protocol, one participant who received IIV4-SD by subcutaneous injection was excluded from the immunogenicity analysis set because of taking a prohibited medication before day 28–35 to treat a SAE
This study showed that high-dose quadrivalent inactivated influenza vaccine (IIV4-HD) was well tolerated and highly immunogenic in healthy adults in Japan ≥65 years of age

Summary

Introduction

Most influenza-related hospitalizations and deaths occur in adults ≥65 years of age.[1]. Influenza vaccination is becoming increasingly important in Japan because it has one of the oldest and most rapidly aging populations globally.[5] Routine vaccination against influenza was instituted in Japan in 2001 for adults ≥65 years of age and adults 60–64 years of age with respiratory, cardiac, or renal disease or infection with human immunodeficiency virus.[6,7]. Since the 2015/16 season, quadrivalent influenza vaccines have been used to vaccinate eligible individuals in Japan.[8] Quadrivalent influenza vaccines contain antigen from two influenza A strains (A/H1N1 and A/H3N2) and both influenza B-strain lineages (Victoria and Yamagata), whereas trivalent vaccines contain the two A strains and a single B-lineage strain. Quadrivalent influenza vaccines were developed to avoid mismatches between the B-strain lineage in trivalent vaccines and the predominant circulating B lineage,[9] which occurred in about one-quarter of influenza seasons between 2000 and 2013.10 Switching from trivalent to quadrivalent influenza vaccines in Japan has prevented an estimated 2030 hospitalizations and 98 deaths each year and saved an estimated 10.75 million US dollars from a societal perspective.[11]

Methods

Results

Conclusion