Content area
Full Text
Introduction
Infections with H7N9 avian influenza virus were identified in human beings in China in early 2013, and by April, 2015, at least 630 laboratory-confirmed infections had been documented, with mortality greater than 30%.1 Evidence was found of increased transmission potential during the second outbreak wave.2 H7N9 viruses bind to avian-type receptors (α2,3-linked sialic acid) and human-type receptors (α2,6-linked sialic acid), although to a lesser extent.3,4 All novel influenza viruses that can infect human beings, including H7N9 avian influenza viruses, pose a threat to human health. Although no respiratory droplet transmission was seen in experiments in ferrets, the dual-receptor specificity could be a crucial feature for sustained human-to-human transmission, especially if adaptive changes occur in the receptor-binding site.5,6 The increased virulence and presence of multiple mammalian adaptation markers and persistence of the virus in the avian reservoir suggest that H7N9 viruses have pandemic potential. These viruses have easily acquired resistance to neuraminidase inhibitors in experimental animal models7,8 and, therefore, specific influenza vaccines remain the main defence against a possible H7N9 pandemic.
Inactivated influenza vaccines (IIVs) administered intramuscularly usually provide short-term and strain-specific humoral immunity. Live attenuated influenza vaccines (LAIVs) are believed to be immunologically superior because they induce diverse types of adaptive immune responses, including serum antibodies, mucosal immunity, and cytotoxic T lymphocytes, which target conserved virus epitopes.9-12 Other advantages of LAIV over IIV are lower costs, quicker manufacturing processes, and a non-invasive route of administration (intranasal spray). These features could help to achieve adequate vaccination coverage during the emergency response to the first wave of a pandemic. We report here the safety and immunogenicity results from a phase 1 clinical trial of an H7N9 LAIV candidate in healthy adult volunteers.
Methods
Study design and participants
This study was a phase 1, double-blind, randomised, placebo-controlled trial done at one site in Saint Petersburg, Russia. The study population comprised healthy adult men and non-pregnant women aged 18-49 years who had received no vaccines in the previous 4 weeks and had not been included in another clinical trial in the previous 3 months (appendix ). All study participants provided written informed consent before the start of the study. The study protocol was approved by the study's independent ethics committee,...