Friday, October 09, 2020

WHO: Candidate Vaccines For Pandemic Preparedness - Oct 2020

Credit NIAID


Twice each year influenza experts gather to discuss recent developments in human and animal influenza viruses around the world. Two weeks ago, in WHO Recommended 2021 Southern Hemisphere Flu Vaccine Composition & Impact Of COVID-19 On Selection, we looked at the WHO's recommendations for next year's Southern Hemisphere seasonal flu vaccine.

Yesterday the WHO released the second report, and today we'll look at their newly updated plans for the development of novel flu vaccines for those viruses that circulate in non-human hosts, and possess some degree of pandemic potential.
Just as there are a growing number subclades of seasonal H3N2 and H1N1 jockeying for dominance in the flu world (see ECDC: Influenza Virus Characterisation - Summary Europe, July 2020), there are dozens of subclades and genotypes of avian and swine flu viruses competing in the wild.
So, when we speak about an avian H5 virus, or a swine H1 virus  - we are really talking about an array of 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.
Over the past 2 decades more than 5 dozen H5H9, H1H3, and H7 candidate vaccine viruses (CVVs) have been selected by WHO for development. Many of these older CVVs are for viruses that no longer circulate in the wild, having been supplanted by newer versions.

Although 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 pandemic vaccine is ever required. 

In their last report - released in February of 2019 - the WHO called for just 1 new CVV (an A/Oman/2747/2019-like A(H9N2)) to be developed.

Although surveillance and reporting of novel flu viruses with zoonotic potential - which is required by the WHO IHR 2005 - is often patchy at best, since the start of the COVID-19 pandemic we've seen a even less reporting than usual (see Flying Blind In the Age Of Pandemics & Emerging Infectious Diseases).

That said, yesterday the WHO released an 11-page update which recommends a two new CVVs be developed; one for Avian A(H5N6) clade isolated in Vietnam, and the other for an EH A/H1N1 clade 1C.2.2 swine virus detected in Germany.

This report also contains information on previously recommended CVVs, and the recent trends and detections of novel viruses around the world over the past 6 months.  I've only posted some excerpts, so follow the link to read it in its entirety.  

I'll have a brief postscript when you return.  

Antigenic and genetic characteristics of zoonotic influenza A viruses and development of candidate vaccine viruses for pandemic preparedness

October 2020

The development of influenza candidate vaccine viruses (CVVs), coordinated by WHO, remains an essential component of the overall global strategy for influenza 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 summarises the genetic and antigenic characteristics of recent zoonotic influenza viruses and related viruses circulating in animals 1 that are relevant to CVV updates. Institutions interested in receiving these CVVs should contact WHO at or the institutions listed in announcements published on the WHO website 2 .


Influenza A(H1)v 5

Influenza A(H1) 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(H1) viruses (designated as A(H1)v viruses) have been documented previously in Asia, Europe and the Americas.

Influenza A(H1)v activity from 25 February to 30 September 2020

One case each of A(H1N1)v and A(H1N2)v human infection was identified in Germany and Brazil, respectively. This was the first case of an A(H1N1)v virus infection reported in Germany and the second case of an A(H1N2)v virus infection reported in Brazil. Additionally, a case of A(H1N1)v virus infection in the Netherlands in September 2019 was identified retrospectively. All individuals had an uncomplicated course of illness.

Antigenic and genetic characteristics of influenza A(H1)v viruses The A(H1N1)v infections were caused by viruses from the 1C.2.2 6 (Eurasian avian-like) swine influenza virus clade, whereas the A(H1N2)v virus was classified as clade 1B.2. Each virus was genetically related to circulating swine influenza viruses from their respective country (Figure 3). The A(H1N1)v 1C.2.2 virus detected in Germany, A/Hessen/47/2020, had an HA1 that differed by 31 amino acids from that of A/Netherlands/3315/2016 from which a clade 1C.2.1 CVV had been recommended. 

Similarly, the A/Hessen/47/2020 HA1 differed from that of A/Hunan/42443/2020, from which a clade 1C.2.3 CVV has been recommended, by 30 amino acids. A/Hessen/47/2020 was recognised poorly by ferret antisera raised against A/Netherlands/3315/2016, but was well recognised by ferret antisera raised against clade 1C.2.2 swine influenza viruses and clade 1C.2.3 influenza viruses (Table 7). The A(H1N2)v virus detected in Brazil could not be isolated for antigenic characterisation.

(Continue . . . )

Presumably any of the currently circulating flu viruses covered by CVVs (and some that aren't) are candidates for sparking the next flu pandemic.  And some viruses - particularly avian H5 and avian H7 - are viewed as capable of producing a more serious pandemic than others, like swine-origin H1N1. 

But swine H1 and H3 viruses are genetically closer to human influenza than their avian counterparts, and would probably have an easier time jumping species (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?). 

The progression of human influenza pandemics over the past 130 years has been H2, H3, H1, H2, H3, H1, H1 . . . .

And swine are also capable of `mixing' flu viruses from other species, increasing their ability to generate new subtypes and/or clades.

So, what they may lack in virulence, they easily make up for with adaptability. 

Over the summer we saw renewed concerns over the evolution and spread of an EA H1N1 `G4' virus in China (see PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China), prompting the CDC, ECDC, and WHO to issue statements and risk assessments. 

FAO/OIE/WHO Tripartite Statement on the Pandemic Risk of Swine Influenza

ECDC Risk Assessment: Eurasian avian-like A(H1N1) swine influenza viruses

The CDC's Responds to the PNAS EA H1N1 `G4' Swine Flu Study

While the concern over the past two decades has been seeing the emergence of a high-mortality (10% CFR+) pandemic from avian H5Nx, H7Nx, or MERS-CoV, the lesson of COVID-19 is that even a 1% CFR can set society back on its heels. 

Today's report is a reminder that influenza evolution and adaptation doesn't stop just because we're already embroiled in a COVID-19 pandemic - and while the threat of another pandemic may feel remote to some - it may be only a few amino acid substitutions away from beginning its world tour.