Abstract Since 2010 the WHO has held a series of informal consultations to explore ways of improving the currently highly complex and time-pressured influenza vaccine virus selection and development ...process. In November 2015 experts from around the world met to review the current status of efforts in this field. Discussion topics included strengthening influenza surveillance activities to increase the availability of candidate vaccine viruses and improve the extent, timeliness and quality of surveillance data. Consideration was also given to the development and potential application of newer laboratory assays to better characterize candidate vaccine viruses, the potential importance of antibodies directed against influenza virus neuraminidase, and the role of vaccine effectiveness studies. Advances in next generation sequencing and whole genome sequencing of influenza viruses were also discussed, along with associated developments in synthetic genomics technologies, evolutionary analysis and predictive mathematical modelling. Discussions were also held on the late emergence of an antigenic variant influenza A(H3N2) virus in mid-2014 that could not be incorporated in time into the 2014–15 northern hemisphere vaccine. There was broad recognition that given the current highly constrained influenza vaccine development and production timeline it would remain impossible to incorporate any variant virus which emerged significantly long after the relevant WHO biannual influenza vaccine composition meetings. Discussions were also held on the development of pandemic and broadly protective vaccines, and on associated regulatory and manufacturing requirements and constraints. With increasing awareness of the health and economic burdens caused by seasonal influenza, the ever-present threat posed by zoonotic influenza viruses, and the significant impact of the 2014–15 northern hemisphere seasonal influenza vaccine mismatch, this consultation provided a very timely opportunity to share developments and exchange views. In all areas, a renewed and strengthened emphasis was placed on developing concrete and measurable actions and identifying the key stakeholders responsible for their implementation.
The influenza viruses Hampson, Alan W; Mackenzie, John S
Medical journal of Australia,
11/2006, Volume:
185, Issue:
S10
Journal Article
Peer reviewed
Human epidemic influenza is caused by influenza type A and B viruses, which continually undergo antigenic change in their surface antigens, haemagglutinin (H) and neuraminidase (N). Influenza ...epidemics are the consequence of small, ongoing antigenic changes known as "antigenic drift", which occurs in both influenza types. Pandemic influenza occurs at irregular and unpredictable intervals, and is the result of a major antigenic change known as "antigenic shift", which occurs only in influenza A. Aquatic birds are the evolutionary hosts of influenza viruses; they harbour many distinct forms or subtypes of influenza A, which are usually present as harmless gut infections. Antigenic shift involves the evolution of a new human influenza A virus through the acquisition of a new haemagglutinin gene encoding a different subtype from an avian influenza, or by the adaptation of an avian virus, causing it to become transmissible between humans. Two subtypes of avian influenza, H5 and H7, can cause severe infections when introduced into domestic poultry. Recently, influenza A/H5N1 viruses have caused widespread outbreaks, starting in Asia and spreading widely to other regions. Avian influenza viruses do not readily infect humans. However, during the past 3 years, more than 250 cases of H5N1 infection of humans have occurred, with associated mortality approaching 60%. It is feared that a new pandemic of human influenza may emerge from this.
Many countries consistently fail to achieve the target influenza vaccine coverage rate (VCR) of 75% for populations at risk of complications, recommended by the World Health Organization and European ...Council. We aimed to identify factors for achieving a high VCR in the scope of four benchmark countries with high influenza VCRs: Australia, Canada, UK and USA.
Publicly available evidence was first reviewed at a global level and then for each of the four countries. Semi-structured interviews were then conducted with stakeholders meeting predefined criteria. Descriptive cluster analyses were performed to identify key factors and pillars for establishing and maintaining high VCRs.
No single factor led to a high VCR, and each benchmark country used a different combination of tailored approaches to achieve a high vaccine coverage. In each country, specific triggers were important to stimulate changes that led to improved vaccine coverage. A total of 42 key factors for a successful influenza vaccination programme were identified and clustered into five pillars: (1) Health Authority accountability and strengths of the influenza programme, (2) facilitated access to vaccination, (3) healthcare professional accountability and engagement, (4) awareness of the burden and severity of disease and (5) belief in influenza vaccination benefit. Each benchmark country has implemented multiple factors from each pillar.
A wide range of factors were identified from an evaluation of four high-performing benchmark countries, classified into five pillars, thus providing a basis for countries with lower VCRs to tailor their own particular solutions to improve their influenza VCR.
Antigenic and genetic analysis of the hemagglutinin of ~13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and ...Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.
Fears of a potential pandemic due to A(H5N1) viruses have focussed new attention on our current vaccines, their shortcomings, and concerns regarding global vaccine supply in a pandemic. The bulk of ...current vaccines are inactivated split virus vaccines produced from egg-grown virus and have only modest improvements compared with those first introduced over 60 years ago. Splitting, which was introduced some years ago to reduce reactogenicity, also reduces the immunogenicity of vaccines in immunologically naïve recipients. The A(H5N1) viruses have been found poorly immunogenic and present other challenges for vaccine producers which further exacerbate an already limited global production capacity. There have been some recent improvements in vaccine production methods and improvements to immunogenicity by the development of new adjuvants, however, these still fall short of providing timely supplies of vaccine for all in the face of a pandemic. New approaches to influenza vaccines which might fulfil the demands of a pandemic situation are under evaluation, however, these remain some distance from clinical reality and face significant regulatory hurdles.
In many countries there is no clear recommendation regarding the preferred route of administration of inactivated influenza vaccines. In a randomised, observer blind study of 720 elderly subjects, a ...split, trivalent influenza vaccine was significantly more immunogenic for both A strains (H3N2 and H1N1,
p
=
0.0016 and 0.003, respectively) when given intramuscularly compared to subcutaneously. This difference was due entirely to a gender effect, with females in the intramuscular (IM) group having a significantly greater serological response than females in the subcutaneous (SC) group for both of these strains. Similar results were seen with local adverse effects. These data suggest that vaccination practices that ensure intramuscular injection are required for optimal administration of influenza vaccines in the elderly.
Human influenza viruses isolated from Australasia (Australia and New Zealand) and South East Asia were analysed to determine their sensitivity to the NA inhibitor drugs, zanamivir and oseltamivir. A ...total of 532 strains isolated between 1998 and 2002 were tested using a fluorescence-based assay to measure the relative inhibition of NA activity over a range of drug concentrations. Based on median IC
50 values, influenza A viruses (with neuraminidase subtypes N1 and N2) were more sensitive to both the NA inhibitors than were influenza B strains. Influenza A viruses with a N1 subtype and influenza B strains both demonstrated a greater sensitivity to zanamivir than to oseltamivir carboxylate, whereas influenza A strains with a N2 subtype were more susceptible to oseltamivir carboxylate. For each of the neuraminidase types, IC
50 values for viruses from Australasia and South East Asia were found to be comparable. Based on the data prior to and following the licensing of the drugs into the respective regions, the use of the NA inhibitors did not appear to have a significant impact on the susceptibility of the viruses tested to zanamivir or oseltamivir carboxylate.
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