OFFLU AVIAN INFLUENZA
MATCHING (OFFLU AIM) INTRODUCTION AND
BACKGROUND
Upda ed: June 2024
Scope: This documen p o ides backg ound in o ma ion and ecommenda ions
on how o use OFFLU AIM
OFFLU a ian in luenza ma ching (AIM) in oduc ion and backg ound las upda ed May 2024
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In oduc ion and backg ound in o ma ion
Cu en ly, some coun ies using accines agains a ian in luenza ha e mechanisms in place o moni o
an igenic changes in ield s ains. Howe e , his in o ma ion is no always sha ed in e na ionally o
made publicly a ailable. The goal o OFFLU A ian In luenza Ma ching (AIM) p ojec (OFFLU AIM), which
s a ed in 2022, is o p o ide imp o ed in o ma ion on an igenic cha ac e is ics o a ian in luenza
i uses (AIV) o suppo accina ion p og ams agains a ian in luenza. I will also assis coun ies u ilising
accines o s ay in o med abou po en ially signi ican changes in he an igenic cha ac e is ics o
ci cula ing s ains. This in o ma ion is also o alue o coun ies conside ing he in oduc ion o
accina ion as an addi ional p e en i e/con ol measu e.
The OFFLU AIM p ojec gi es cu en epidemiological, gene ic, and an igenic in o ma ion on AI i uses
ci cula ing in di e en geog aphic egions. Da a is analysed in a ha monised way and made eely
accessible. In o ma ion comes om a ange o sou ces including published in o ma ion, da a om
coun ies moni o ing o AIV including po en ial an igenic a ian s, accine challenge ials, speci ic
an igenic ca og aphy and o he in elligence ha wa an s conside a ion by coun ies using o
conside ing accina ion.
Se e al coun ies ha e been elying on accina ion agains Gs/Gd lineage HPAI i uses o con ol
ecu en ou b eaks in poul y and educe he numbe o zoono ic in ec ions. Ea ly adop e s o
accina ion include China, Egyp , Indonesia, Vie nam and Bangladesh – all places whe e hese i uses
we e ci cula ing in poul y be o e accina ion commenced. Recen ly, and especially due o he
inc eased h ea posed by clade 2.3.4.4b i uses, many coun ies in La in and Cen al Ame ica ha e
adop ed accina ion and some coun ies in Asia a e conside ing upda ing hei accine s a egies. Some
coun ies (e.g., F ance and Hong Kong SAR), al hough ee om HPAI, use p e en i e accina ion,
because o he high isk o in ec ion e.g. om spillo e om wild bi ds, and he h ea which i poses o
he indus y.Se e al o he coun ies used accines b ie ly in poul y and un egis e ed accine is being
applied in some o he coun ies, a p ac ice ha OFFLU does no ecommend.
Vaccina ion in poul y agains a ian in luenza is commonly conduc ed using adju an ed egg-based
inac i a ed whole- i us accines, usually p oduced elying on i uses enginee ed by e e se gene ics o
inc ease i us yield and he sa e y o ope a o s. O he accine echnologies a e also in use o unde
de elopmen , including i al ec o accines such as hose using he he pes i us o u keys (HVT) as he
ec o , subuni accines (used cu en ly in F ance and Egyp ), sel -ampli ying RNA accines, DNA
accines, i us-like pa icles, and eplicon pa icles. Some o hese accines, especially hose based on a
li e i al ec o , can induce b oade c oss p o ec ion agains he e ologous s ains o A(H5Nx) HPAI i us
because hey also s imula e cell media ed immuni y (Palya e al., 2018). In some cases, he
hemagglu inin gene inse o subuni and ec o accines a e compu a ionally op imized o u he
expand he b ead h o eac i i y. This means ha an igens used in hese accines do no necessa ily
equi e upda ing as equen ly as hose con ained in adi ionally manu ac u ed inac i a ed whole- i us
accines. Ne e heless, i espec i e o he accine echnology, i is s ill c i ical o moni o accina ed
locks o de ec in ec ion and o cha ac e ise i uses by unde aking a ho ough assessmen o hei
an igenic cha ac e is ics.
The ocus o his i s OFFLU AIM epo is on HPAI i uses o he H5Nx sub ype om he Gs/Gd lineage.
These HPAI i uses eme ged in China in 1996 and ha e been ci cula ing as high pa hogenici y i uses
OFFLU a ian in luenza ma ching (AIM) in oduc ion and backg ound las upda ed May 2024
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since ha ime. They ha e e ol ed h ough gene ic d i in o mul iple 5 h o de HA clades
1
and ha e
easso ed o p oduce mul iple sub ypes and geno ypes. These i uses ha e caused se e al episodes o
in e con inen al ansmission since 2005 due mainly o dispe sal by wild bi ds, p esumably a e
spillback o in ec ion om domes ic poul y in places whe e wild bi ds and poul y mix eely. O he
ini ial 10 clades ha eme ged in he ea ly 2000s, only de i a i es o clade 2 i uses ha e pe sis ed and
con inue o e ol e. Vi uses de ec ed ecen ly belong o clades 2.3.4.4b (widesp ead globally excep
Oceania), 2.3.2.1a (Sou h Asia) and “2.3.2.1c
2
” (Sou heas Asia). Vaccines a ge ing each o hese clades
ha e been de eloped, wi h each cu en ly in use in a leas one coun y.
This epo should be ead in conjunc ion wi h o he epo s such as EFSA Scien i ic Opinion on
accina ion, WHO gene ic and an igenic cha ac e is ics o in luenza A i uses wi h zoono ic po en ial,
and OFFLU a ian in luenza composi ion mee ing epo s. I is c ucial o no e ha he ocus o he VCM
epo is p epa a ion o candida e accine an igens o use in humans o pandemic p epa edness, bu i
p o ides impo an in o ma ion on ecen ly de ec ed i uses. I also p o ides in o ma ion on an igenic
and gene ic cha ac e is ics o i uses wi h he o me ob ained h ough he hemagglu ina ion inhibi ion
assays using e e an ise a immunised agains human candida e accine e e ence an igens. An igenic
cha ac e isa ion based on he use o e e an ise a may yield di e en esul s o one conduc ed wi h
chicken an ise a immunised agains a ian accine an igens.
OFFLU AIM is building ne wo k capaci y o an igenically es i uses using an ise a aised in chickens
agains poul y accine an igens, o su oga e (gene ically simila ) an igens when he accine s ain is
no a ailable. The i s epo p o ided in o ma ion on he an igenic cha ac e is ics o con empo a y
clade 2.3.4.4b i uses agains clade 1, clade 2.2, clade 2.3.4, clade 2.3.2.1, clade 2.3.2.1a i uses and
clade 2.3.4.4c accine an igens. In he second epo , an igenic cha ac e is ics o clade 2.3.4.4b i uses
om a b oade geog aphical egion a e included as well as con empo a y clade 2.3.2.1a s ains. This
wo k is con inually expanding, and subsequen epo s will include mo e cu en ly used accine
an igens o su oga es and upda e in o ma ion as i becomes a ailable co e ing a wide ange o
con empo a y ci cula ing clade i uses.
Two ypes o e en s a e ele an when conside ing an igenic changes in ci cula ing AIVs a a
na ional/ egional le el. The i s is he e olu ion o i uses whe e accines a e being used wi hin he
coun y o egion – also e med an igenic d i , leading o accine escape, meaning accines may no
longe be e icacious agains he i uses which con inue o ci cula e. Examples include he an igenic
a ia ion ha occu ed in Egyp ian clade 2.2 i uses and Indonesian clade 2.1 i uses, and hei
de i a i es (A a a e al., 2012, Swayne e al., 2015). In o he ins ances, he same accine an igen has
been used and emained app op ia e o e mul iple yea s (e.g., accines used in Vie Nam agains clade
1 i uses and hei de i a i es om 2005 onwa ds).
1
Smi h GJ, Donis RO, Wo ld Heal h O ganiza ion, Wo ld O ganisa ion o Animal Heal h, Food Ag icul u e
O ganiza ion, H5 E olu ion Wo king G oup. Nomencla u e upda es esul ing om he e olu ion o a ian in luenza
A(H5) i us clades 2.1.3.2a, 2.2.1, and 2.3.4 du ing 2013-2014. In luenza O he Respi Vi uses 2015;9(5):271-6.
A ailable a : h p://onlinelib a y.wiley.com/doi/10.1111/i .12324/epd
2
Clade 2.3.2.1c i uses ha e e ol ed in o di e en sublineages since hey we e las o mally classi ied in 2014. An
upda ed, s anda dised clade nomencla u e o i uses ha p e iously ell wi hin clade 2.3.2.1c is being de eloped
bu has no ye been accep ed o mally. Ne e heless, i uses om Indonesia ha we e p e iously e e ed o as
2.3.2.1c ha e been e e ed o as 2.3.2.1e in OFFLU and WHO documen s o se e al yea s (see oo no e 2), based
on ad ice om molecula gene icis s, gi en hey di e om hose ound in mainland Sou h Eas Asia. Fu he
changes in classi ica ion a e expec ed o i uses wi hin clade 2.3.2.1c and OFFLU will ad ise once he new
nomencla u e has been accep ed and adop ed.
OFFLU a ian in luenza ma ching (AIM) in oduc ion and backg ound las upda ed May 2024
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The second ype o e en is he in oduc ion o a s ain o i us ha di e s signi ican ly om exis ing,
dominan ly ci cula ing i uses such as he in oduc ion o clade “2.3.2.1c2” i uses in Vie Nam leading
o co ci cula ing wi h he p e iously dominan clade 1.1.2 i uses. In such cases, an igenic changes in he
no el s ain eme ged elsewhe e, p io o he i uses’ expansion in o he new egion (i.e. by wild bi d
mo emen o ade). This is exempli ied by he ecen in oduc ion o A(H5N1) clade 2.3.4.4b o
Indonesia whe e accines in use a e designed o p o ec agains A(H5N1) clade “2.3.2.1c 2” i uses ha
s ill ci cula e he e. In some coun ies he clade 2.3.4.4b has eplaced he exis ing s ain(s) bu in o he
coun ies bo h p e-exis ing and new s ains co-ci cula e, o he new s ain is es ic ed o only pa o
he coun y.
The in o ma ion in his documen is gene ic in na u e and depends on epo s o in o ma ion om
indi idual coun ies on ci cula ing i uses. I does no imply p e e ence o speci ic accines o
p oduc s. All coun ies conside ing accina ion should use he in o ma ion in his documen as a
supplemen o da a collec ed locally on ci cula ing s ains and on a ailable accines when de e mining
he mos app op ia e accines and accina ion s a egies o apply.
OFFLU scien is s u ge all coun ies o con inue sha ing in o ma ion on no el s ains o i us, especially
hose associa ed wi h clinical and i ological accine ailu es suspec ed o being an igenic a ian s so
ha OFFLU can con inue o p o ide up- o-da e in o ma ion on i uses in ci cula ion. Whe e possible,
and especially i he e a e suspicions o accine escape a ian s, i uses and gene sequences should be
sha ed wi h OFFLU e e ence labo a o ies o allow ull an igenic and gene ic cha ac e iza ion.
Much o he in o ma ion in his documen is o ele ance o inac i a ed whole i us accines which a e
he mos used a ian in luenza accines globally), a he han o he echnology accines. We cau ion
eade s om d awing conclusions on he e icacy o accines solely based on an igenic dis ance.
Al hough i ’s commonly accep ed ha he p o ec i e e icacy o inac i a ed whole i us accines is
signi ican ly a ec ed by an igenic d i . The e is a deg ee o ole ance ha no el accine echnologies
ha e, in e ms o changes in an igenic iden i y and highly immunogenic o mula ions migh compensa e
o he na ow b ead h o eac i i y o con en ional accines by inducing high an ibody i e s.
To ha end, se ological moni o ing o accina ed locks o e idence o immuni y o accines is s ongly
ecommended especially o accines ha gene a e a s ong humo al esponse. Tes ing o accina ed
locks is impo an o ensu e ha accines a e s imula ing a su icien immune epose in bi ds o
p o ide p o ec ion.
OFFLU scien is s, FAO and WOAH a e a ailable o suppo coun ies wi h accina ion in poul y and
p o ide echnical ad ice and scien i ic in o ma ion. Please con ac sec e a ia @o lu.o g
OFFLU a ian in luenza ma ching (AIM) in oduc ion and backg ound las upda ed May 2024
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Re e ences
A a a A, Sua ez D, Kholosy SG, Hassan MK, Nase S, Selim A, Dauphin G, Kim M, Yilma J, Swayne D, Aly
MM. E olu ion o highly pa hogenic a ian in luenza H5N1 i uses in Egyp indica ing p og essi e
adap a ion. A ch Vi ol. 2012 Oc ;157(10):1931-47. doi: 10.1007/s00705-012-1385-9. Epub 2012 Jul 4.
PMID: 22760662.
Palya V, Ta á -Kis T, Walkóné Ko ács E, Kiss I, Homonnay Z, Ga din Y, Ke ész K, Dán Á. E icacy o a
Recombinan Tu key He pes i us AI (H5) Vaccine in P e en ing T ansmission o He e ologous Highly
Pa hogenic H5N8 Clade 2.3.4.4b Challenge Vi us in Comme cial B oile s and Laye Pulle s. J Immunol
Res. 2018 No 21;2018:3143189. doi: 10.1155/2018/3143189. PMID: 30584541; PMCID: PMC6280313.
Swayne DE, Sua ez DL, Spackman E, Jadhao S, Dauphin G, Kim-To che i M, McG ane J, Wea e J,
Daniels P, Wong F, Selleck P, Wiyono A, Ind iani R, Yupiana Y, Sawi i Si ega E, P aji no T, Smi h D,
Fouchie R. An ibody i e has posi i e p edic i e alue o accine p o ec ion agains challenge wi h
na u al an igenic-d i a ian s o H5N1 high-pa hogenici y a ian in luenza i uses om Indonesia. J
Vi ol. 2015 Ap ;89(7):3746-62. doi: 10.1128/JVI.00025-15. Epub 2015 Jan 21. PMID: 25609805; PMCID:
PMC4403412.
Links o OFFLU AIM documen s
OFFLU A ian in luenza echnical ac i i y accina ion page
Concep no e OFFLU AIM p ojec - Ap il 2022
OFFLU AIM p esen a ion – Feb ua y 2023
OFFLU AIM pilo epo – Oc obe 2023