Phase I/II Randomized Double-Blind Study of the Safety and Immunogenicity of a Nonadjuvanted Vero Cell Culture-Derived Whole-Virus H9N2 Influenza Vaccine in Healthy Adults

Abstract

dStudies on candidate pandemic vaccines against avian influenza viruses have focused on H5N1, but viruses of other subtypes, such as A/H9N2, are also considered to have pandemic potential. We investigated the safety and immunogenicity of two immunizations with one of five different antigen doses (ranging from 3.75 to 45 g of hemagglutinin antigen) of a nonadjuvanted whole-virus G9 lineage H9N2 influenza virus vaccine in healthy adults aged 18 to 49 years. The antibody responses were measured by hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays. To investigate a hypothesis that previous exposure to H2N2 viruses in subjects born in or before 1968 might prime for more robust antibody responses to H9N2 vaccination than that in subjects born after 1968, a post hoc age-stratified analysis of antibody responses was done. Both vaccinations in all dose groups were safe and well tolerated. No vaccine-related serious adverse events were reported, and the majority of the adverse reactions were rated as mild. The rates of injection site reactions were lower in the 3.75-g-and 7.5-g-dose groups than those in the higher-dose groups; the rates of systemic reactions were similar across all dose groups. The seroprotection rates among the different dose groups 21 days after the second immunization ranged from 52.8% to 88.9% as measured by HI assay, from 88.7% to 98.1% or 82.7% to 96.2% as measured by MN assay (MN titer cutoffs, 1:40 and 1:80, respectively), and from 94.2% to 100% as measured by SRH assay. Higher antibody responses were not induced in subjects born in or before 1968. These data indicate that a nonadjuvanted whole-virus H9N2 vaccine is well tolerated and immunogenic in healthy adults. (This study has been registered at ClinicalTrials.gov under registration no. NCT01320696.) A number of avian influenza virus subtypes have caused zoonotic infections in humans, including those of subtypes H5N1 (1), H9N2 (2), and, most recently, H7N9 (3) and H10N8 (4). Because the human population is largely immunologically naive to such viruses, there are concerns that a pandemic situation might occur if any of these viruses gains the capacity for efficient human-to-human transmission. The development of candidate pandemic vaccines to counter the threat of a pandemic resulting from avian influenza viruses is thus an important part of global pandemic preparedness programs (5, 6). To date, this effort has been concentrated largely on the development of candidate pandemic vaccines based on influenza viruses of the H5N1 subtype. A number of clinical studies have demonstrated whole-virus inactivated H5N1 vaccines to be immunogenic in adult, elderly, and pediatric populations without a requirement for adjuvantation (7-11). In the present study, we extend the clinical investigation of nonadjuvanted whole-virus avian influenza vaccines to include a vaccine against the H9N2 influenza virus subtype, which is enzootic in poultry across the Middle East and Asia and is considered to have pandemic po...

The Correlation of IFN <i>γ</i> to the Preferential Isolation of Influenza Type B over Type A Viruses in Madin Darby Canine Kidney Cells

“…It has been proposed that despite the fact that influenza type A and type B are structurally and functionally similar, they show fundamental differences in the ways in which the host recognizes these pathogens [3]. In this study, the aim was to determine factors that influence the preferential isolation of influenza type B [3], a finding supporting the faster restriction and clearance of influenza type B virus.…”

“…In this study, the aim was to determine factors that influence the preferential isolation of influenza type B [3], a finding supporting the faster restriction and clearance of influenza type B virus. The IRF 3 is part of a large transcription factor family which has IRF 1 -9, and these are involved in regulation of cell cycle, apoptosis and tumor suppression [27].…”

“…At the present time, there are 18 HA and 11 NA which can undergo re-assortment or mutations to give rise to new or variant strain among influenza type A viruses. It was in this regard that strains such as the case of influenza B had formed a homogeneous group, which started to diverge antigenically into two distinct lineages, whose first representatives were B/Victoria/2/87 and B/Yamagata/16/88, as the Victoria and Yamagata lineages respectively [3]. This nomenclature system was adapted after the World Health Organization (WHO) where B denotes for the type of Influenza virus, Victoria as the place of origin, 2 as the strain serial number and 87 as the year of isolation.…”

“…There have also been other pandemics, namely: the Asian Influenza (A/H2N2) of 1957, Hong Kong Influenza A (H3N2) of 1968 [3]. The global burden of influenza is believed to cause 300,000 deaths annually [5].…”

Vaccination against H9N2 avian influenza virus reduces bronchus‐associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection

“…Therefore, additional models mimicking natural infection are required for evaluation of the pathogenicity of H9N2 virus. Several trials of inactivated and live attenuated vaccines against H9N2 virus in mice and humans have been reported . We previously reported that whole particle vaccines prepared from a virus library that contained 144 combinations of 16 HAs and 9 neuraminidases (NAs) conferred protective immune responses against H5N1 and H7N7 highly pathogenic influenza viruses in cynomolgus macaques .…”