WHO: Candidate Vaccines For Pandemic Preparedness - Sept 2019

Credit NIAID

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Twice each year influenza experts gather to discuss recent developments in human and animal influenza viruses around the world. Last Saturday - in WHO Announces 2 Strain Changes For 2020 Southern Hemisphere Flu Vaccine - we looked at the WHO's recommendations for next year's Southern Hemisphere seasonal flu vaccine.

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 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.

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.

Over the past 2 decades more than 5 dozen H5, H9, H1, H3, 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 3 new CVVs (2 avian, 1 Swine variant) to be developed.

Late yesterday the WHO released 9 page update, which recommends a new H7N9 CVV (A/Gansu/23277/2019-like) be developed, and characterizes novel viruses detected around the globe over the past 6 months.

While novel flu activity has been pretty slow in 2019, we are informed by this report that several new subclades of HPAI H5 have recently emerged, and that:

An update of this nomenclature has been made during 2019 defining additional clades within existing clades 2.3.2.1c and 2.3.4.4. and will be published on the WHO website by the end of year.

A few excerpts from the latest WHO report follow, but you'll want to follow the link to read it in its entirety. I'll have a postscript when you return. 

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

September 2019

The development of influenza candidate vaccine viruses (CVVs), coordinated by 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 animals 1 that are relevant to CVV updates. Institutions interested in receiving these CVVs should contact WHO at gisrs-whohq@who.int or the institutions listed in announcements published on the WHO website 2 .

(SNIP)

Influenza A(H7)
 
Human infections with avian influenza A(H7N9) viruses were first reported to WHO on 31 March 2013. This summary provides updates on the characterisation of A/Anhui/1/2013 HA lineage A(H7) viruses and the current status of the development of corresponding CVVs.

Influenza A(H7) activity from 18 February 2019 to 24 September 2019

One human case of HPAI A(H7N9) infection was detected in China in this period. HPAI A(H7N9) viruses were also detected in environmental samples collected in the poultry market epidemiologically linked to the human case. Since their emergence, there have been 1568 confirmed human infections with A/Anhui/1/2013 HA lineage A(H7N9) viruses.

Antigenic and genetic characteristics of influenza A(H7) viruses

The HA proteins of the A(H7N9) viruses isolated from the infected human and associated poultry market had 16 amino acid substitutions relative to previously characterized viruses and available CVVs (Figure 1).

Correspondingly, these viruses were not inhibited well by antisera raised against available CVVs or previously described wild type viruses (Table 3).

Influenza A(H7) candidate vaccine viruses
 
Based on the current antigenic, genetic and epidemiologic data, development of a new A/Gansu/23277/2019-like CVV is proposed. Availability of A(H7N9) CVVs is listed in Table 4.

        (Continue . . . )


China's massive H5+H7 poultry vaccination campaign, which began in the summer of 2017, has been a remarkable success and avian flu reports have been greatly reduced. But the downside to poultry vaccination is that viruses continue to mutate - often masked by the vaccine - and over time the vaccine becomes less effective, as new variants emerge. 

Last May, in Eurosurveillance: The re-emergence of HPAI H7N9 Human Infection in Mainland China, 2019, we saw some early indications that this latest human H7 case in China showed distinct evolutionary changes.

That  report warned:

This suggests that H7N9 viruses might still circulate in poultry at a low level in limited locations. In addition, several immune escape mutations, which had not been detected in previously reported HPAI H7N9 viruses, occurred in the HA1 proteins of these viruses (Table 1). The antigenic features of these HPAI H7N9 viruses may differ from the current HPAI H7N9 candidate vaccine strain. 

A reminder that evolution doesn't stop just because we're enjoying a lull in avian flu activity - and while the next pandemic threat may be hidden - it may be only a few amino acid substitutions away from beginning its world tour.