Immunogenicity and safety of a cell culture-derived inactivated quadrivalent influenza vaccine (NBP607-QIV): A randomized, double-blind, multi-center, phase III clinical trial in adults and elderly subjects

Abstract

Background: The influenza B virus has two lineages; Yamagata and Victoria. The two lineages are antigenically distinct and it is difficult to expect cross-protection between the lineages. Actually, the mismatch between circulating influenza B viruses and vaccine strains has been occurred frequently. The cell-culture system for the production of influenza vaccine can contribute to improve vaccine strain selection and expand vaccine supplies. We investigated the immunogenicity and safety of cell culturederived quadrivalent inactivated influenza vaccine (NBP607-QIV) in adults and elderly subjects.Methods: A randomized controlled phase III trial was undertaken in 10 university hospitals in the Republic of Korea (Clinical trial Number-NCT02467842). Adults (aged 19-59 years) and elderly subjects (aged 60 years) were randomly assigned in a 2:1:1 ratio to NBP607-QIV versus cell culture-based trivalent inactivated influenza vaccine-Yamagata (NBP607-Y) and cell culture-based trivalent inactivated influenza vaccine-Victoria (NBP607-V). Immunogenicity was assessed 3 weeks after vaccination by hemagglutination inhibition assay. Safety was assessed for 6 months post-vaccination: solicited adverse events (AEs) for 7 days, unsolicited AEs for 21 days and serious adverse events (SAEs) for 6 months. AEs were sub-classified as adverse drug reactions (ADRs) according to the causality.Results: A total of 1,503 participants were randomly assigned to NBP607-QIV (n D 752), NBP607-Y (n D 373) and NBP607-V (n D 378). The seroconversion rates of NBP607-QIV were 52.4%, 51.2%, 43.7% and 55.8% against A/H1N1, A/H3N2, B/Yamagata and B/Victoria, respectively. Non-inferiority against shared strains and superiority against alternate-lineage B strains were demonstrated for NBP607-QIV vs. NBP607-Y and NBP607-V. A total of 730 reactions occurred in 324 (43.1%) subjects of NBP607-QIV group. Majority of ADRs was solicited (99.2%) and mild (90.3%) in intensity. In adults (aged 19-59 years), solicited local AEs were slightly more frequent in NBP607-QIV group than NBP607-Y or NBP607-V group (40.9%, 33.4% and 32.5%, respectively). One SAE was observed among NBP607-QIV group, which was considered to be unrelated to the study vaccine within 3 weeks of vaccination and no vaccine-related SAEs were reported up to 6 months after vaccination.Conclusions: NBP607-QIV is a safe, well-tolerated and immunogenic influenza vaccine in Korean adults and elderly subjects.

Quadrivalent Vaccines for the Immunization of Adults against Influenza: A Systematic Review of Randomized Controlled Trials

“…Subsequently, 11 articles were excluded because of the following reasons: six showed overlapping data, three did not have available full texts and two did not present relevant results. Therefore, at the end of the selection process, 24 RCTs [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ] met the inclusion criteria and were eventually included ( Figure 1 ).…”

“…Amongst the included studies, all RCTs have been completed. Eleven studies (45.8%) were published between 2011 and 2016 [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], and thirteen (54.2%) after 2016 [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Seven studies (26.9%) were conducted in multiple countries [ 25 , 26 , 28 , 29 , 39 , 41 , 45 ].…”

Adverse events of interest following influenza vaccination, a comparison of cell culture-based with egg-based alternatives: English sentinel network annual report paper 2019/20

“…In the stratified analyses, we found that QIVc was associated with higher RIs of AEIs within seven days of vaccination when compared to QIVe in adults aged 18 to 64 years and to aTIV in older adults aged ≥65 years. This is an unanticipated finding, as phase III trials showed the safety profile of QIVc was similar to two comparator TIVc, with only slightly higher incidence of solicited local AEIs [ 32 , 33 ], and post-licensure studies have repeatedly shown that the safety of QIVc is similar to cell-based TIV (TIVc), which in turn is similar to egg-based TIV [34] .…”

Post-transplant Viral Respiratory Infections in the Older Patient: Epidemiology, Diagnosis, and Management

“…Inactivated influenza vaccine is widely recommended to prevent infection in transplant candidates, recipients, close contacts, and healthcare workers [68]. In recent years, trivalent formulations have been available containing two A and one B strain; however, given the frequent co-circulation of a second B strain, quadrivalent vaccines have been developed [69][70][71]. Immunogenicity of influenza vaccine depends on the type of transplant population studied, immunosuppression, and time from transplant.…”