Diversity of circulating H5N1 Clades – Credit WHO
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Influenza A viruses are categorized by two proteins they carry on their surface; their HA (hemagglutinin) and NA (neuraminidase), resulting in subtypes like H5N1, H7N9, or H3N2. While the list continues to expand, currently we know of 18 different HA proteins and 11 different NA proteins, making many different subtype combinations possible, although many of these combinations have yet to be observed in nature.
And it gets more complicated, as within each subtype, multiple strains may appear. A recent example came within the H1N1 subtype, which was the backbone of our seasonal flu for 90 years (1918-2008), but was supplanted by a radically different H1N1 virus in 2009.
Within each strain, there are often genetic groupings called clades, and within each clade- subclades – and within each of these, many variants may exist. This constant evolution of influenza viruses is illustrated quite nicely in the NIAID video Influenza: Get the (Antigenic) Drift.
Many of these variants (even entire clades) die off over time, unable to compete successfully with other – more biologically `fit’ – entrants in this evolutionary race. But many of those that can infect humans – and persist and thrive in the wild – are perceived as posing a potential public health threat.
So from time to time, the World Health Organization makes recommendations on new candidate influenza vaccine viruses for investigation and consideration, in case one of these emerging viruses takes off. The last time was early in the fall of 2013 (see WER: Antigenic & Genetic Comparisons Of Zoonotic Flu Viruses And Development Of Vaccine Candidates), where the WHO proposed that 4 new H5N1 candidate vaccine viruses be developed.
Yesterday, the WHO released a new review of currently circulating zoonotic influenza viruses, and their recommendations for two new vaccine virus candidates (H5N1 & H7N9). No new vaccine virus candidates for H7N9 are announced, and investigative work has just begun on the recently observed H10N8 virus.
February 2014
The development of representative candidate influenza vaccine viruses, coordinated by the World Health Organization (WHO), remains an essential component of the overall global strategy for pandemic preparedness.Zoonotic influenza viruses continue to be identified and evolve both genetically and antigenically, leading to the need for update of candidate vaccine viruses for pandemic preparedness purposes. Evaluation of the genetic and antigenic characteristics of these viruses, their relationship to existing candidate vaccine viruses, and their potential risks to public health, justify the need to select and develop new candidate vaccine viruses.
Selection and development of a candidate vaccine virus represents a first step only towards timely vaccine production and does not imply a recommendation for initiating manufacture. National authorities may consider the use of one or more of these candidate vaccine viruses for pilot lot vaccine production, clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.
This document summarizes the genetic and antigenic characteristics of recent zoonotic influenza viruses from humans and related viruses circulating in animals and updates the availability of candidate vaccine viruses. Institutions that wish to receive these candidate vaccine viruses should contact WHO at gisrs-whohq@who.int or the institutions listed in announcements published on the WHO website1.
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Influenza A(H5N1) candidate vaccine viruses
Based on the available antigenic, genetic and epidemiologic data, an A/environment/Hubei/950/2013-like (clade 7.2) candidate vaccine virus is proposed. The available and proposed candidate A(H5N1) vaccine viruses are listed in Table 3. National authorities may consider the use of one or more of these candidate A(H5N1) vaccine viruses for pilot lot vaccine production, clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.As the viruses continue to evolve, new A(H5N1) candidate vaccine viruses may be developed.
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Influenza A(H9N2) candidate vaccine viruses
Based on the current antigenic, genetic and epidemiologic data, an A/Hong Kong/308/2014-like candidate vaccine virus is proposed. The available A(H9N2) candidate vaccine viruses are listed in Table 7. National authorities may consider the use of one or more of these candidate A(H9N2) vaccine viruses for pilot lot vaccine production, clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.As the viruses continue to evolve, new A(H9N2) candidate vaccine viruses may be developed.
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Influenza A(H10N8)
Three cases of human infection with avian influenza A(H10N8) viruses were reported from Jiangxi Province, China, with onset dates from December 2013 to February 2014. All of these individuals had severe disease and two have died. All had reported contact with poultry or contaminated environments. To date, genetic information from one virus isolate is available, which showed all genes to be of avian origin and the internal genes to be derived from A(H9N2) viruses currently circulating widely in poultry in China.This virus is susceptible to the neuraminidase inhibitor class of antiviral drugs. Information on the prevalence and distribution of A(H10N8) viruses in poultry in the region is limited, thus the assessment of its impact on public health is difficult. At this time, the virus is being evaluated for its growth and antigenic properties and diagnostic reagents are being prepared. WHO is monitoring the situation closely.
Having updated candidate influenza vaccine viruses on hand can shave weeks (or even months) off the vaccine development timetable, should one of these clades suddenly take off.
But with so many clades in play – and the likelihood that older candidate viruses would produce an ineffective vaccine against newer strains – it doesn’t make sense to try to make a huge stockpile of any of these vaccines.
Influenza viruses are constantly moving targets, and until an effective universal vaccine can be developed, the reality is we are always going to be playing catch-up with a very nimble foe.
