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22 Jan 2017

Recommended #composition of #influenza virus #vaccines for use in the 2017 southern hemisphere influenza season (@WHO, Jan. 22 ‘17)

 

Title: Recommended #composition of #influenza virus #vaccines for use in the 2017 southern hemisphere influenza season.

Subject: Human Influenza Viruses, southern hemisphere flu season, recommended composition for human vaccines.

Source: World Health Organization (WHO), full PDF document: (LINK).

Code: [     ]

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Recommended composition of influenza virus vaccines for use in the 2017 southern hemisphere influenza season

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September 2016

The World Health Organization (WHO) convenes technical consultations(1) in February and September each year to recommend viruses for inclusion in influenza vaccines(2) for the northern and southern hemisphere influenza seasons, respectively. This recommendation relates to the influenza vaccines for use in the forthcoming southern hemisphere 2017 influenza season. A recommendation will be made in February 2017 relating to vaccines that will be used for the northern hemisphere 2017-2018 influenza season. For countries in equatorial regions, epidemiological considerations influence which recommendation (February or September) individual national and regional authorities consider appropriate.

 

Seasonal influenza activity, January 2016 – August 2016

  • Between January and August 2016, low to widespread influenza activity was reported in Africa, the Americas, Asia, Europe and Oceania predominantly due to the circulation of influenza A(H1N1)pdm09 and B with some outbreaks of A(H3N2) viruses.
  • In the northern hemisphere, influenza activity was high from January until April/May and declined thereafter with the exception of several countries in the Americas and Asia.
  • In the southern hemisphere, activity remained low until March after which moderate to high activity was reported by a number of countries. 

 

Northern hemisphere temperate region

  • Regional and widespread influenza activity was reported until April/May with influenza A(H1N1)pdm09 and B viruses co-circulating in most countries of Europe and several countries in Asia.
  • In addition, a few countries in Europe and Asia, including China, reported regional outbreaks of A(H3N2) influenza virus in the early part of the year.
  • North America reported high influenza activity caused by A(H1N1)pdm09 from January until May, type B viruses from January until June and A(H3N2) from March until May.

 

Southern hemisphere temperate region

  • Influenza activity was low in the early part of the year.
  • Regional and widespread activity was reported from May onwards in southern Africa with early predominance of influenza B viruses, followed by the circulation of influenza A(H3N2) and A(H1N1)pdm09 viruses.
  • Regional to widespread activity was reported in the southern cone of the Americas from March onwards with influenza B virus cocirculating with A(H1N1)pdm09 and regional A(H3N2) activity was reported in May.
  • Oceania reported low circulation of viruses until March.
  • High A(H1N1)pdm09 activity was reported in Papua New Guinea in March and in Fiji A(H3N2) activity was high in May.
  • Australia reported high activity of A(H3N2) with co-circulation of influenza B virus from June to September.

 

Tropical and subtropical regions

  • Influenza activity was variable but low overall in the tropical and subtropical regions of Africa.
  • In Egypt there was an influenza B virus outbreak from March to May.
  • In West Africa there was low influenza activity; however Ghana reported local to regional A(H3N2) activity from April to July.
  • In Central Africa widespread activity was reported by the Democratic Republic of Congo from April to July and the Central African Republic from July to September.
  • Influenza activity was variable in tropical America with a few countries reporting regional A(H1N1)pdm09 activity between March and June.
  • Influenza activity was variable in tropical and subtropical Asia with regional outbreaks of A(H1N1)pdm09 followed by co-circulation of A(H3N2) and B viruses reported by several countries in tropical Asia and some countries in the Middle East from January until April.
  • Detailed information by country of the extent and type of seasonal influenza activity worldwide is available on the WHO website: http://www.who.int/entity/influenza/vaccines/virus/recommendations/201609_influenzaactivitytable.pdf 

 

Zoonotic influenza infections caused by A(H5), A(H7N9), A(H9N2), A(H1N2)v and A(H3N2)v viruses

  • From 23 February 2016 to 26 September 2016, four human cases of A(H5N6) infection were reported by China and ten human cases of A(H5N1) infection were reported by Egypt.
  • The disease onset date for two of the cases from Egypt predated this reporting period.
  • Highly pathogenic avian influenza A(H5) is present in poultry in both countries.
  • Since December 2003, a total of 870 human cases of A(H5) infection with 458 deaths have been confirmed in 16 countries.
  • To date there has been no evidence of sustained human-to-human transmission.  
  • During this period 77 additional human cases of avian influenza A(H7N9) virus infection have been reported to WHO by China.
  • Since February 2013, a total of 798 cases with 320 deaths have been reported.  
  • Nine A(H9N2) human cases were reported during this period, eight in China and one in Egypt.
  • Three of the cases from China, including a fatal case, had disease onset dates that predated the reporting period.
  • Viruses from cases in China belong to the A/chicken/Hong Kong/Y280/97 genetic lineage.
  • No data are available for the virus from Egypt where A/quail/Hong Kong/G1/97 lineage viruses circulate in poultry.
  • During this period, four cases of A(H1N2)v, three in the United States of America and one retrospective case in Brazil, and 19 cases of A(H3N2)v, 18 in the United States of America and one retrospective case in Viet Nam, were reported. 

 

Antigenic and genetic characteristics of recent seasonal influenza viruses

  • Influenza A(H1N1)pdm09 viruses
    • The vast majority of A(H1N1)pdm09 viruses collected from February 2016 to August 2016 fell into the phylogenetic clade 6B.
    • Most recently circulating viruses belonged to genetic subclade 6B.1. 
    • A small proportion of viruses circulating globally belonged to subclade 6B.2. Subclade 6B.2 viruses were detected most frequently in China, although 6B.1 viruses predominated. 
    • Antigenic characteristics of A(H1N1)pdm09 viruses were assessed with panels of post-infection ferret antisera and human paediatric, adult and older adult pre- and post-vaccination sera in haemagglutination inhibition (HI) assays.
    • HI assays with ferret antisera indicated that almost all recent A(H1N1)pdm09 viruses were antigenically indistinguishable from the vaccine virus A/California/7/2009. 
    • However, representative 6B.1 and 6B.2 viruses were poorly inhibited by some post-vaccination adult human serum pools (Table 1).
    • Furthermore, geometric mean post-vaccination HI titres of paediatric sera against some representative 6B.1 and 6B.2 A(H1N1)pdm09 viruses were reduced significantly compared to HI titres to the A/California/7/2009 vaccine virus, although this was not consistently observed for adult and older adult serum panels.
  • Influenza A(H3N2) viruses
    • A(H3N2) viruses collected from February to August 2016 fell into the phylogenetic clades 3C.2 and 3C.3.
    • Viruses in subclade 3C.2a predominated in most regions of the world with the majority of these viruses having further changes in the haemagglutinin (HA) (N171K, I406V, G484E), now referred to as subclade 3C.2a1.
    • Subclade 3C.3a has continued to circulate but represented a lower proportion of viruses circulating during this reporting period except in the United States of America where they predominated. Viruses in genetic subclade 3C.3b were rarely detected. 
    • Antigenic characteristics of A(H3N2) viruses were assessed with panels of post-infection ferret antisera in HI and virus neutralisation assays.
    • Antigenic characterization of 3C.2a viruses continued to be technically challenging because many viruses had low or undetectable haemagglutination activity in the presence of oseltamivir carboxylate, added to circumvent agglutination by the virus neuraminidase.
    • Virus neutralisation assays supplemented HI assays for the antigenic characterization of viruses.
    • Most recent A(H3N2) 3C.2a viruses were well inhibited by ferret antisera raised against cell culture-propagated reference viruses in subclade 3C.2a including A/Hong Kong/4801/2014 or A/Michigan/15/2014.
    • These antisera also inhibited a majority of viruses in subclades 3C.2a1 (including those with an additional N121K HA substitution), 3C.3a and 3C.3b. 
    • Egg propagation is known to introduce additional changes in HA that can affect antigenicity.
    • Such changes have been particularly problematic for recent A(H3N2) viruses.
    • Ferret antisera raised against egg-propagated 3C.2a viruses, including A/Hong Kong/4801/2014, generally inhibited recently circulating viruses better than antisera raised against egg-propagated A/Switzerland/9715293/2013 virus or other recent egg-propagated viruses. 
    • Human serology studies were performed using serum panels from adults and older adults who had received seasonal quadrivalent inactivated vaccines with the composition recommended for the southern hemisphere 2016 season (A/California/7/2009 (H1N1)pdm09-like, A/Hong Kong/4801/2014 (H3N2)-like, B/Brisbane/60/2008-like and B/Phuket/3073/2013-like antigens).
    • Geometric mean HI titres of antibodies against representative recent A(H3N2) viruses were somewhat reduced compared to HI titres against the cell-propagated vaccine virus.
    • In microneutralisation tests with a subset of serum panels and viruses, geometric mean titres of antibodies against recent representative A(H3N2) viruses were similar to those against the cell-propagated vaccine virus.
  • Influenza B viruses
    • Influenza B viruses of the B/Victoria/2/87 and the B/Yamagata/16/88 lineages co-circulated at equivalent levels in some countries, while viruses of the B/Victoria/2/87 lineage predominated in many countries. 
    • Almost all of the HA gene sequences of B/Victoria/2/87 lineage viruses fell into genetic clade 1A.
    • In HI assays, recent viruses were well inhibited by post-infection ferret antisera raised against either B/Brisbane/60/2008 or B/Texas/2/2013 cell culture-propagated viruses.
    • B/Brisbane/60/2008 was recommended for use in vaccines for the 2016-2017 northern hemisphere influenza season. 
    • The HA gene sequences of the vast majority of B/Yamagata/16/88 lineage viruses fell into genetic clade 3.
    • In HI assays, recently circulating B/Yamagata/16/88 lineage viruses were well inhibited by post-infection ferret antisera raised against the cell culture-propagated B/Phuket/3073/2013 virus (clade 3).
    • B/Phuket/3073/2013 was recommended for use in quadrivalent vaccines for the 2016-2017 northern hemisphere influenza season. 
    • Human serology studies were performed using serum panels from adults and older adults who had received seasonal quadrivalent inactivated vaccines of the composition recommended for the northern hemisphere 2015-2016 season (A/California/7/2009 (H1N1)pdm09-like, A/Switzerland/9715293/2013 (H3N2)-like, B/Phuket/3073/2013-like and B/Brisbane/60/2008-like antigens) or  for the southern hemisphere 2016 season (A/California/7/2009 (H1N1)pdm09-like, A/Hong Kong/4801/2014 (H3N2)-like, B/Brisbane/60/2008-like and B/Phuket/3073/2013-like antigens).
    • Geometric mean HI titres of antibodies against some representative recent B/Victoria/2/87 lineage viruses were reduced compared to HI titres against the cell-propagated vaccine virus B/Brisbane/60/2008.
    • When tested against representative recent B/Yamagata/16/88 lineage viruses, geometric mean HI titres were reduced for some viruses compared to HI titres against the eggpropagated vaccine virus B/Phuket/3073/2013. 

 

Resistance to influenza antiviral drugs

  • Neuraminidase inhibitors
    • The detection of viruses with reduced susceptibility to the neuraminidase inhibitors was very rare among the >9000 viruses tested during this reporting period.
    • Of >4000 influenza A(H1N1)pdm09 viruses tested for susceptibility to the neuraminidase inhibitors, 69 carried an H275Y amino acid substitution in neuraminidase which conferred highly reduced inhibition by oseltamivir and peramivir.
    • Forty-one of these viruses were detected in Japan (41/1467; 2.8%) and sixteen were detected in the United States of America (16/2331; 0.7%).
    • The majority of A(H1N1)pdm09 viruses carrying H275Y amino acid substitutions were from patients receiving oseltamivir treatment. 
    • All of the A(H3N2) viruses tested were sensitive to neuraminidase inhibitors.  
    • All but two influenza B/Yamagata/16/88 lineage viruses were sensitive to neuraminidase inhibitors.
    • One virus carried an I221V amino acid substitution in neuraminidase that resulted in reduced peramivir inhibition, while the other contained an I348T amino acid substitution in neuraminidase that conferred reduced oseltamivir inhibition. 
    • All but four of the influenza B/Victoria/2/87 lineage viruses were sensitive to neuraminidase inhibitors.
    • Three viruses from Lao People’s Democratic Republic carried an H134N amino acid substitution in neuraminidase and one virus from Malaysia carried a G104E amino acid substitution in neuraminidase. Both substitutions conferred reduced or highly reduced inhibition by all four neuraminidase inhibitors – oseltamivir, zanamivir, peramivir and laninamivir. 
  • M2 inhibitors
    • M gene sequencing of A(H1N1)pdm09 and A(H3N2) viruses revealed that all viruses analysed had S31N amino acid substitutions in their M2 proteins which is known to confer resistance to the M2 inhibitors, amantadine and rimantadine.

 

Recommended composition of influenza virus vaccines for use in the 2017 southern hemisphere influenza season

  • Influenza A(H1N1)pdm09 viruses, which predominated in many countries, co-circulated with A(H3N2) and influenza B viruses during the period February 2016 – August 2016. 
  • Influenza A(H1N1)pdm09 viruses were associated with outbreaks in many countries. Influenza A(H1N1)pdm09 viruses were antigentically indistinguishable by post-infection ferret antisera but in studies with human post-vaccination sera representative 6B.1 and 6B.2 viruses were distinguishable from the A/California/7/2009 vaccine virus.
  • Influenza A(H3N2) viruses were associated with outbreaks in many countries. The majority of recent viruses were antigenically related to cell culture-propagated 3C.2a A/Hong Kong/4801/2014-like viruses. 
  • Influenza B viruses of the B/Victoria/2/87 and the B/Yamagata/16/88 lineages co-circulated, with viruses of the B/Victoria/2/87 lineage predominating in many countries. Most B/Victoria/2/87 lineage viruses were antigenically and genetically closely related to B/Brisbane/60/2008 and B/Texas/2/2013. The majority of recent B/Yamagata/16/88 lineage viruses were antigenically and genetically closely related to B/Phuket/3073/2013.
  • It is recommended that trivalent vaccines for use in the 2017 southern hemisphere influenza season contain the following:
    • an A/Michigan/45/2015 (H1N1)pdm09-like virus;
    • an A/Hong Kong/4801/2014 (H3N2)-like virus; and
    • a B/Brisbane/60/2008-like virus.
  • It is recommended that quadrivalent vaccines containing two influenza B viruses contain the above three viruses and a B/Phuket/3073/2013-like virus.
  • Lists of egg propagated candidate vaccine viruses (CVVs) suitable for use in vaccines produced in either eggs or cell culture, as well as cell culture-propagated CVVs suitable for use in vaccines produced in cell culture are available on the WHO website3. A list of reagents for vaccine standardization, including those for this recommendation, can also be found on the WHO website. CVVs for zoonotic influenza viruses are updated on the same website.
  • As in previous years, national or regional authorities approve the composition and formulation of vaccines used in each country. National public health authorities are responsible for making recommendations regarding the use of the vaccine. WHO has published recommendations on the prevention of influenza4.

(…)

WHO provides fortnightly updates5 of the global influenza activity. Other information of influenza surveillance can be found on the WHO Global Influenza Programme website6. 

(…)

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{1} http://www.who.int/influenza/vaccines/virus/en/ 

{2} Description of the process of influenza vaccine virus selection and development available at:   http://www.who.int/gb/pip/pdf_files/Fluvaccvirusselection.pdf 

{3} http://www.who.int/influenza/vaccines/virus/candidates_reagents/home

{4} http://www.who.int/wer/2012/wer8747.pdf 

{5} http://www.who.int/influenza/surveillance_monitoring/updates/en/ 

{6} http://www.who.int/influenza  

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Keywords: WHO; Worldwide; Updates; Seasonal Influenza; Vaccines.

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