#12,784
As we discussed yesterday, twice each year influenza experts gather to discuss recent developments in human and animal influenza viruses around the world.
Yesterday we looked at the WHO's recommendations for next year's Southern Hemisphere seasonal flu vaccine, while today we'll look at their selections for the development of novel flu vaccines for those viruses that possess some degree of pandemic potential.Just as there are currently more than a half dozen subclades of seasonal H3N2 jockeying for dominance in the flu world (see The Enigmatic, Problematic H3N2 Influenza Virus), there are dozens of subclades and genotypes of avian and swine flu viruses competing in the wild.
Simply put, the H5N1 virus in Egypt (Clade 2.2.1.2) isn't isn't the same as the H5N1 virus in Nigeria (Clade 2.3.2.1c), or the one in Bangladesh (Clade 2.3.2.1a).So, when we speak of the avian H5N1 virus, or H7N9 - we are really talking about multiple genetically distinct variants - each on their own evolutionary path. And a vaccine developed against one strain of the same subtype may not prove protective against another.
Since H5N1 emerged in 2003, three dozen H5N1 candidate vaccine viruses (CVVs) have been selected by WHO for development. While it can be expensive, having a proven CVV already tested and approved can save months of valuable time if mass production and distribution of a vaccine is ever required.
Similarly there are 11 H7N9 CVVs, and 6 H9N2 CVVs either developed or in the pipeline. The latest report from the WHO, released yesterday, can be found at:
Antigenic and genetic characteristics of zoonotic influenza viruses and candidate vaccine viruses developed for potential use in human vaccines
28 September 2017
This summary provides a review on the zoonotic influenza virus activity and virus characterization, and describes the current status of the development of candidate vaccine viruses for pandemic preparedness purposes. It is meant to provide guidance for national authorities and vaccine companies on the selection of candidate viruses for use in vaccine development.
September 2017
pdf, 923kb
According to this latest report, since the last review (see WHO: Candidate Vaccines For Pandemic Preparedness) 6 months ago, no new H5N1, H7N9, or H9N2 viruses have appeared requiring development into new CVVs.
On the swine flu front, however, we've seen several new variants turn up, which are discussed in the following excerpts from yesterday's 14-page report:
Influenza A(H1N2) variants (v)4
Influenza A(H1) viruses circulate in swine populations in many regions of the world. Depending on geographic location, the genetic characteristics of these viruses differ. Human infections with swine A(H1) viruses have been documented for many years.
Influenza A(H1N2)v activity from 28 February to 25 September 2017
Two cases of A(H1N2)v were detected in the United States of America during this reporting period. Both were in children who developed mild disease following direct contact with pigs. Phylogenetic analysis of the HA gene of A/Ohio/24/2017 showed it was of the swine H1 alpha lineage similar to viruses isolated from swine in North America in recent years. A/Ohio/35/2017 had a seasonal, human-like H1 HA gene segment that belonged to the delta 2 lineage of swine influenza viruses. This HA gene is closely related to the HA genes of influenza viruses currently circulating in swine in the United States of America (Figure 2).
Antigenic and genetic characteristics of influenza A(H1N2)v viruses
Antigenic testing demonstrated that ferret antisera raised against current CVVs reacted poorly with these two A(H1N2)v viruses. The reactivity of pooled, adult human sera collected post-vaccination with the 2016-2017 vaccine was also reduced against these viruses in haemagglutination inhibition assays (Tables 4 and 5).
Influenza A(H1)v candidate vaccine viruses
Based on the current antigenic, genetic and epidemiologic data, new CVVs generated from A/Ohio/24/2017-like and A/Ohio/35/2017-like viruses are proposed. The available A(H1)v CVVs are listed in Table 6.
Influenza A(H3N2)v
Influenza A(H3N2) viruses are enzootic in swine populations in most regions of the world. Depending on geographic location, the genetic and antigenic characteristics of these viruses differ. Human infections with swine influenza A(H3N2) viruses have been documented in Asia, Europe and North America5.
Influenza A(H3N2)v activity from 28 February to 25 September 2017
Thirty one cases of A(H3N2)v were detected in the United States of America during this reporting period. The virus from one case in Texas had an HA gene belonging to the IV-A cluster, closely related to A(H3N2) viruses currently circulating in North American swine.
The remaining cases of A(H3N2)v virus infection were identified in North Dakota [1], Pennsylvania [1], Maryland [13] and Ohio [15] from July to September following exposure to swine at agricultural fairs. With the exception of three adult cases, all others were among children twelve years of age or younger. No human-to-human transmission was identified. These A(H3N2)v viruses had HA genes derived from a seasonal human H3 virus that was probably introduced to swine by humans in 2010 (Figure 3). The viruses were closely related to A(H3N2)v viruses infecting humans in Ohio and Michigan in 2016 and viruses known to circulate in swine in the United States of America.
Antigenic and genetic characteristics of influenza A(H3N2)v viruses
Characterisation of the cluster IV-A virus revealed that ferret antisera raised against wild type viruses and CVVs reacted well with this virus. Antigenic testing of the viruses with the 2010 human-like H3 gene showed reduced inhibition by post-infection ferret antisera raised against the nearest CVV, IDCDC-RG55C, and seasonal A(H3N2) viruses. Pooled, adult post-vaccination antisera reacted with these viruses at titres that were reduced compared to those against homologous vaccine viruses. A pool of sera collected from vaccinated children showed greater reductions in titre compared with pooled adult sera (Table 7).
Influenza A(H3N2)v candidate vaccine viruses
Based on the available antigenic, genetic and epidemiologic data, a new CVV based on an A/Ohio/13/2017-like virus is proposed. The available A(H3N2)v CVVs are listed in Table 8.
Since the influenza HA subtypes that commonly circulate in swine (H1, H2, H3) are also the same that have caused all of the human pandemics going back 130 years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), they are generally regarded as having less far to `jump’ to humans than do many avian viruses.
Which is precisely how the H1N1 pandemic virus emerged in 2009, after kicking around (and reassorting in) swine herds for a decade or longer.All of which makes the development of swine CVVs, like the ones proposed yesterday, a critical part of pandemic preparedness. For more on the global emergence of novel swine flu viruses, you may wish to revisit:
EID Journal: Transmission Of Swine H3N2 To Humans At Agricultural Exhibits - Michigan & Ohio 2016
A Reminder About The `Other' Novel Flu Threat
J. Virol: Novel Reassortant Human-like H3N2 & H3N1 Influenza A Viruses In Pigs
MMWR: Investigation Into H3N2v Outbreak In Ohio & Michigan - Summer 2016
