Flu is a slippery virus, a tough vaccine target and a challenge to contain…

Figure 1. World’s greatest real-time H3N2 Flu tracking. Highlighted is this season’s A/Hong Kong/4801/2014-like H3N2 vaccine virus. The “X” at the top of the tree is the A/Singapore/INFIMH-16-0019/2016 virus recommended for our 2018 Flu vaccine [6] https://nextflu.org/h3n2/3y/

Much was made of a regrettable interview earlier in the week about the Australian equivalent Flu vaccine.

Some of the headlines included…

  • “Cut-price flu jabs too weak to work”
  • “Cheaper flu shot behind grim toll”
  • “Cheap’ flu vaccine blamed for outbreak”
  • “‘Weak’ flu vaccine could explain Australia’s horror sickness season which saw hundreds die and 217,000 people contract the illness”
  • “Cheap flu jab not up to task”

Ouch.

Prof. Paul Van Buynder was quoted as saying that “Australia suffered the worst flu season on record because officials chose a cheap vaccine that did not protect the elderly”. Many disagreed. I disagree.

Flu vaccines are safe but pretty crap (scientific definition) and adding in a new one licensed for use only in those above 65 years of age, that contains 4X as much active ingredient but is made the same way and as likely to suffer from the same issues described below will – at best – reduce the proportion of crappiness but not overcome it. You can read more about this topic in our latest Conversation article.[9]

It’s kinda hard to identify what this new vaccine’s absolute effectiveness is, just that its better than standard dose vaccines. To date, this higher dose vaccine has been trivalent, which seems a step backwards from this season;’ quadrivalent vaccine but perhaps the thinking is that Flu B is not as much of a disease threat among the elderly.

But 2017 was more about suboptimal vaccine and diversifying Flu virus.

This Flu season (dominated by influenza [Flu] A virus H3N2) moved quickly in Australia this year. Data and expert commentary didn’t keep pace with community and media need.

We do know a few things about the massive Australian influenza season that was…

  1. Very few Aussies got vaccinated – if we can extrapolate from a new Victorian study then…[1] 
    1. 27% of Australians (with confirmed influenza) got a needle
    2. 6% of infected children (those less than 15 years old) were vaccinated
  2. A/H3N2 viruses detected over the past few years [4] have been mostly classified into a phylogenetic clade (groupings of “leaves” seen on phylogenetic trees like that in Figure 1) called 3C2.a. 3C2.a currently exists as 5 smaller genetically diverse groups called clades.[3,4,5] Lab tests have struggled to nail down the extent of ANY antigenic diversity among these groups because of problems with their agglutination ability.[6]
    1. Ferret antibody-containing sera raised to lab grown A/Hong Kong/4801/2014-like H3N2 lab virus inhibited growth of this season’s H3N2s.
    2. Ferret antibody-containing sera raised to egg-adapted A/Hong Kong/4801/2014-like H3N2 vaccine virus struggled to inhibit growth of this season’s H3N2s.
    3. Human antisera were not as inhibitory with this season’s H3N2 viruses, likely reflecting what’s happening in vaccinated humans
    4. Currently circulating H3N2s were better inhibited by ferret antisera raised against A/Singapore/INFIMH-16-0019/2016 H3N2 virus raised antisera (Figure 1), and it is this strains which is being recommended for our southern hemisphere’s next season’s Flu vaccine.[6] ] 
  3. Only 33% of vaccinated Aussies were effectively protected.[1] Proportions differed between the Flu types and age.[1]
    1. 16% of children were protected against Flu A or B compared to 39% of adults (15-64 yo)
    2. Flu vaccination was 5% effective against viruses ascribed to the A/H3N2 clade called 3C2.a but 19% effective against 3C2.a1
    3. Flu vaccination was 45% effective against Flu B/Yamagata strains
  4. There’s no evidence that I’ve seen for a massive increase in new Flu testing that would account for the massive increase in Flu cases in 2017
    1. there is new rapid testing capacity rolling out, but also replacement of existing capacity. It would be good to see data on how much new testing contributed to the tally of lab confirmed Flu cases in Australia in 2017 
  5. A recent study found new information about one known mutation which occurs in the Flu A/H3N2 viruses as they are being grown in eggs – part of them becoming egg-adapted. Huge amounts of virus are needed to make vaccine; it’s grown up in fertilised (embryonated) eggs, inactivated and made into the vaccine. One change, L194P, renders the HA protein less antigenic (less noticeable to our immune system) so it doesn’t trigger the immune response we’d hoped for
    1. change at position 194 in the hemagglutinin protein in which a leucine [L] has been changed as the result of nucleotide mutation(s) to a proline  [P]; written as L194P)

So these really highlight how complex the Flu vaccination situation is. It also underlines that we really need to get away from egg-based Flu vaccines and towards something that elicits a more robust, long-lasting and protective immune response ideally bringing in more of the the memory and regulatory capability of the T-Cell arm of our immune system. Ultimately, a vaccine that would only need one or a short course of shots that protect us for years, or even life, as do other vaccines.

It won’t be here in 2018 or in time for the northern hemisphere season which is not yet firing off.[7,8]

In the meantime, Australia is likely to get a new vaccine (the U.S. have had it since 2009, Canada since last year) added to its armamentarium to help reduce illness and death among the Flu infected elderly. 

References…

  1. Low interim influenza vaccine effectiveness, Australia, 1 May to 24 September 2017
    https://www.ncbi.nlm.nih.gov/pubmed/29090681
  2. A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine
    http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006682
  3. Real-time tracking of influenza virus evolution – nextflu
    https://nextflu.org/h3n2/3y/
  4. Seasonal influenza circulation patterns and projections
    for Sep 2017 to Sep 2018
    https://www.biorxiv.org/content/early/2016/09/21/076638
  5. Seasonal influenza circulation patterns and projections for 2016-2017
    https://www.biorxiv.org/content/early/2016/09/21/076638
  6. Recommended composition of influenza virus vaccines for use in the 2018 southern hemisphere influenza season
    http://www.who.int/entity/influenza/vaccines/virus/recommendations/201709_recommendation.pdf
  7. https://www.cdc.gov/flu/weekly/
  8. https://www.gov.uk/government/statistics/weekly-national-flu-reports
  9. Here’s why the 2017 flu season was so bad
    https://theconversation.com/heres-why-the-2017-flu-season-was-so-bad-86605

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