Thursday, February 22, 2018

WHO: Recommended Composition Of 2018-2019 Northern Hemisphere Flu Vaccine

The Wide World Of Flu Activity


Twice each year influenza experts gather to discuss recent developments in human and animal influenza viruses around the world, and to decide on the composition of the next influenza season’s flu vaccine. 
While never an easy task, this has become more difficult over the years - particularly with seasonal H3N2 - as the number of genetically distinct groups in circulation has continued to rise (see The Enigmatic, Problematic H3N2 Influenza Virus).
This year marks the 50th consecutive year that H3N2 has been in circulation, having first emerged as a pandemic strain in 1968.  That's a longer reign than any other seasonal flu virus that we are aware of - and in order to survive that long and avoid running out of hosts due to acquired community immunity - it has been forced to continually reinvent itself.
NIAID has a terrific 3-minute video that shows how influenza viruses drift over time, and why the flu shot must be frequently updated, which you can view at this link.
Between the growing diversity among H3N2 viruses, and problems with egg-based vaccine manufacturing introducing small antigenic changes in the vaccine (see PLoS Path.: A Structural Explanation For The Low VE Of Recent H3N2 Vaccines), the track record for the H3N2 component of the seasonal flu vaccine has grown increasingly dismal.

Last years VE (Vaccine Effectiveness) against H3N2, as reported by the CDC's MMWR, was estimated at 34%.  This year's mid-season estimate from the CDC - issued a week ago - only found 25% VE against H3N2, and for certain age groups (adolescents (9-17), and adults 50 and older) - showed no statistically significant protection from the vaccine.
The one bright spot was a 51% VE for children aged 6mos to 8 years. 
Luckily, the other influenza A component - H1N1 - while it continues to evolve, has remained comparatively stable, requiring only 1 strain change since it emerged as a pandemic strain in 2009.  Similarly, Influenza B strains are slow to change, although we've seen some diversity among the Victoria lineage of late.
Due to the time it takes to manufacture and distribute a vaccine, decisions on which strains to include must be made at least six months in advance, which means the composition of next fall's Northern Hemisphere’s vaccine must be decided upon now.
This week the World Health Organization brought together representatives from  GISRS (Global Influenza Surveillance and Response System), along with members of OFFLU (the OIE/FAO Network on Animal Influenza), and other experts to recommend what flu strains to include in next fall's vaccine.
Not unexpectedly, the WHO is recommending a change to the H3N2 component which has performed poorly the past couple of years.  They have also swapped out the old Victoria lineage Influenza B virus for a new strain. 
The following excerpt comes from a much longer and more detailed (8-page) WHO release called: 

Recommended composition of influenza virus vaccines for use in the 2018-2019 northern hemisphere influenza season
There was considerable variation in the predominant virus type circulating in different regions during the period September 2017 to January 2018. Influenza B viruses predominated in many countries, while A(H3N2) viruses predominated in some and A(H1N1)pdm09 viruses circulated widely in Africa, Asia, parts of Europe and in the Middle East.
The vast majority of influenza A(H1N1)pdm09 viruses belonged to genetic subclade 6B.1 and were antigenically indistinguishable from the vaccine virus A/Michigan/45/2015.
Influenza A(H3N2) viruses were associated with outbreaks in several countries. The majority of recent viruses were antigenically related to cell culture-propagated A/Hong Kong/4801/2014-like and A/Singapore/INFMH-16-0019/2016-like viruses; they reacted poorly with ferret antisera raised to many egg-propagated clade 3C.2a viruses but somewhat better to egg-propagated A/Singapore/INFMH-16-0019/2016-like viruses.
Influenza B viruses of the B/Yamagata/16/88 lineage predominated in most regions of the world. Recent B/Yamagata/16/88 lineage viruses were antigenically and genetically closely related to the vaccine virus B/Phuket/3073/2013. Influenza B viruses of the B/Victoria/2/87 lineage were detected in low numbers but a substantial and increasing proportion of these viruses, containing a two amino acid deletion in their HAs, were antigenically distinguishable from the vaccine virus B/Brisbane/60/2008 but closely related to B/Colorado/06/2017.
It is recommended that quadrivalent vaccines for use in the 2018-2019 northern hemisphere influenza season contain the following:
- an A/Michigan/45/2015 (H1N1)pdm09-like virus;
- an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus;
- a B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage); and
- a B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage).
It is recommended that the influenza B virus component of trivalent vaccines for use in the 2018-2019 northern hemisphere influenza season be a B/Colorado/06/2017-like virus of the B/Victoria/2/87-lineage.

The new H3N2 component is the same one that will be used this year in the Southern Hemisphere flu vaccine, which should give us some idea of how well it works. Hopefully it will improve the VE against H3N2 next fall, but concerns remain over the impact of egg-propagated flu vaccines.
Most recent A(H3N2) viruses were well inhibited by ferret antisera raised against cell culture-propagated reference viruses in clade 3C.2a, including A/Hong Kong/4801/2014, A/Michigan/15/2014 and A/Singapore/INFIMH-16-0019/2016.
In contrast, a significantly lower proportion of A(H3N2) viruses was inhibited well by ferret antisera raised against egg-propagated 3C.2a reference virus A/Hong Kong/4801/2014. Recent A(H3N2) viruses were better inhibited by a ferret antiserum raised against the egg-propagated reference virus A/Singapore/INFIMH-16-0019/2016 compared to ferret antisera raised against other recent egg-propagated A(H3N2) viruses.
While the flu vaccine is far from perfect, it – along with practicing good flu hygiene (washing hands, covering coughs, & staying home if sick) – still remains your best strategy for avoiding the flu and staying healthy this winter.
None of this guarantees you won't get the flu.  
But some protection against a potentially deadly virus beats no protection - any day of the week.

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