While we talk about novel influenza viruses like H5N1 and H7N9 as if they were single entities, in truth, each subtype designates a large and growing family of viruses.
In the 20 years since HPAI H5N1 (A/goose/Guangdong/1/96) first appeared in China, we've seen dozens of H5N1 clades, subclades, and variants emerge around the world.
Simply put, the H5N1 virus that circulates in Egypt isn't the same as the H5N1 virus that occurs in Vietnam, or China, or Nigeria. And even within these regions, there can be considerable diversity in the virus.
As an example, last May in Fatal H5N1 Infection In Tigers By Different Reassortant Viruses - China we looked at a report on three recent (2014-2015) H5N1 related tiger deaths in a Yunnan Province zoo which occurred over an 18 month period.
Remarkably, all three viruses were different clades of H5N1.
The constellation of HPAI H5 viruses has grown even greater over the past three years with the emergence of new H5N6, H5N8, and H5N2 subtypes - all carrying the H5 clade 184.108.40.206 HA gene.
And within each of these new subtypes, new clades, subclades, and variants continue to evolve.
Along side this proliferation of HPAI H5 viruses, we are also seeing similar evolution and growing diversity among H7N9, H9N2, and a number of swine variant viruses (H1N1v, H3N2v, etc.) as well.
The good news is that many of these variants (even entire clades) will die off over time, unable to compete successfully with newer – more biologically `fit’ – entrants in this evolutionary race.
The bad news is, as new strains emerge, vaccine candidates based on older viruses become less effective, and must be continually updated.
So from time to time, the World Health Organization makes recommendations on new candidate influenza vaccine viruses (CVVs) for investigation and consideration, in case one of these emerging viruses begins to show pandemic potential.
Last week the WHO published the following summary of novel flu activity and recommendations for new candidate vaccine viruses.
Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness
The development of candidate influenza vaccine viruses (CVVs), coordinated by the World Health Organization (WHO), remains an essential component of the overall global strategy for pandemic preparedness.
Selection and development of CVVs are the first steps towards timely vaccine production and do not imply a recommendation for initiating manufacture. National authorities may consider the use of one or more of these CVVs for pilot lot vaccine production, clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.
Zoonotic influenza viruses continue to be identified and evolve both genetically and antigenically, leading to the need for additional CVVs for pandemic preparedness purposes. Changes in the genetic and antigenic characteristics of these viruses relative to existing CVVs, and their potential risks to public health, justify the need to select and develop new CVVs.
This document summarizes the genetic and antigenic characteristics of recent zoonotic influenza viruses and related viruses circulating in animals1 that are relevant to CVV updates. Institutions interested in receiving these CVVs should contact WHO at email@example.com or the institutions listed in announcements published on the WHO website.
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This document describes four distinct HPAI H5 clades reported during 2016.
- Clade 220.127.116.11
- Clade 18.104.22.168a
- Clade 22.214.171.124c
- Clade 126.96.36.199 (H5N1, H5N2, H5N6, H5N8)
Based on these detection's three new H5 candidate vaccine viruses are proposed.
Influenza A(H5) candidate vaccine viruses
Based on the available antigenic, genetic and epidemiologic data, new A/Hubei/29578/2016-like (188.8.131.52), A/chicken/Guiyang/1153/2016-like (184.108.40.206c) and A/chicken/Ghana/20/2015-like (220.127.116.11c) CVVs are proposed. The available and pending A(H5) CVVs are listed in Table 6. As the viruses continue to evolve, new A(H5) CVVs may be developed.
There are currently seven H7N9 vaccine virus candidates available, and no new candidates are proposed in this report. Similarly, there are six H9N2 vaccine virus candidates in storage, and no new H9N2 vaccine virus candidates are recommended.
Over the past year we've seen new swine variant influenza activity, including 18 H3N2v infections in the United States. There are currently 3 H1N1v and 3 H3N2v candidate vaccines, but the WHO is recommending a new H3N2v vaccine candidate be added.
Influenza A(H3N2)v candidate vaccine viruses
Based on the available antigenic, genetic and epidemiologic data, a new A/Ohio/28/2016-like A(H3N2)v CVV is proposed. The available A(H3N2)v CVVs are listed in Table 11. As the viruses continue to evolve and as new data are generated, new A(H3N2)v CVVs may be developed.
Having updated candidate influenza vaccine viruses on hand can shave weeks (or even months) off the vaccine development timetable, should one of these viruses suddenly take off.
But with so many variants 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.