OFFLU A ian In luenza Vaccine Ma ching (AIM) o poul y
accines: H5Nx execu i e summa y
Summa y .................................................................................................................. 2
Findings ................................................................................................................... 4
Clade 2.3.4.4b ....................................................................................................... 4
Eu ope ............................................................................................................... 5
A ica ................................................................................................................. 5
No h Ame ica .................................................................................................... 6
Cen al and Sou h Ame ica .................................................................................. 6
Asia ................................................................................................................... 6
Clade 2.3.4.4h ....................................................................................................... 7
Clade 2.3.2.1c1 ...................................................................................................... 8
Clade 2.3.2.1a ....................................................................................................... 9
Conclusions ........................................................................................................ 10
Re e ences ............................................................................................................. 11
(Oc obe 2024)
Disclaime : This echnical epo uses published nomencla u e which hasn’ ecen ly been upda ed (widely used by
many coun ies a p esen (i.e. “GISAID clade”)1 bu no ecen ly upda ed) AND unpublished nomencla u e p oposed by
he WHO/FAO/WOAH H5 Nomencla u e Wo king G oup2 (i.e. p o isional Nex clade/LABEL clade). Th oughou he epo ,
he use o he di e en nomencla u es is disc imina ed by oo no es.
This epo p o ides he poin o iew o independen OFFLU expe s and does no necessa ily e lec he posi ion o he
pa en o ganisa ions FAO and WOAH.
Summa y
E ec i eness o poul y accina ion agains high pa hogenici y a ian in luenza (HPAI)
depends on he a ailabili y and p ope use o sui able accines acco ding o age and hos
species. An igenic a ia ion in eme ging ield s ains may ende exis ing accines less
e ec i e. This is pa icula ly ue o accines ha ely p ima ily on he an ibody-based
(humo al) immune esponse (e.g, con en ional inac i a ed accines, subuni accines).
The OFFLU-AIM p ojec ’s goal is o p o ide in o ma ion on he di e si y o i al su ace
p o eins (an igenic di e si y) in ci cula ing HPAI i uses ha could impac he e ec i eness
o exis ing accines. This p ojec ocuses on he goose/Guangdong/1/96-lineage A(H5Nx)
i uses (Gd/Gd) which ha e di e si ied gene ically since hei eme gence. I is impo an o
highligh ha an igenic and gene ic e olu ion a e no always conco dan (Kok e al., 2024),
hus, he in o ma ion in his epo is de i ed om mul iple sou ces including an igenic
es ing conduc ed a FAO and WOAH e e ence labo a o ies. Con inuous moni o ing and
ull cha ac e isa ion o i uses, including an ibody moni o ing, especially in coun ies
using accina ion, a e c ucial.
The HPAI Gd/Gd clade 2.3.4.4b A(H5N1) i uses a e a signi ican h ea o global poul y
p oduc ion. These i uses ci cula e widely in di e se wild bi d species ac oss Eu asia,
pa s o A ica, and he Ame icas, wi h equen spillo e s in o poul y and subsequen
sp ead is acili a ed by poo biosecu i y and poul y mo emen , wi h se e e impac s o
poul y p oduc ion. Ou b eaks in accina ed poul y ha e been epo ed wi hin he pas
yea in F ance and con inuous cha ac e isa ion o ci cula ing i uses is ecommended.
• Clade 2.3.4.4b i uses ha e eplaced o he clades in sub-Saha an A ica, wi h
ecen i uses indica ing some an igenic di e si y. Enhanced diagnos ic e alua ion,
and imely elease o global da a a e equi ed o unde s and accine equi emen s
ac oss A ica.
• Clade 2.3.4.4b i uses con inue o cause ou b eaks in poul y in Eu ope and
ci cula e in wild bi ds. Vi uses isola ed om wild bi ds ha e been an igenically
s able. P e en a i e accina ion has been used in ducks in F ance o e win e
2023/2024; howe e , ou b eaks in accina ed poul y ha e been epo ed.
• Ou b eaks o a ian in luenza con inue in comme cial poul y and backya d locks in
he USA and Canada, p edominan ly caused by he H5N1 sub ype. Limi ed epo s
on he an igenic cha ac e is ics o ecen i uses a e no sugges i e o an igenic
change. In Cen al and Sou h Ame ica, clade 2.3.4.4b i uses we e i s de ec ed in
la e 2022, ha e sp ead widely, and ha e disp opo iona ely impac ed he backya d
poul y sec o .
• Clade 2.3.4.4b i uses a e widesp ead in Asia, wi h mul iple incu sions in o poul y
and, in some coun ies, co-ci cula ion wi h o he -clade i uses. E idence o
an igenic he e ogenei y has been obse ed, highligh ing he impo ance o i al and
an igenic moni o ing, o he ea ly de ec ion o di e gen e olu ion.
• Clade 2.3.2.1a i uses con inue o be de ec ed in Sou h Asia. Recen i uses a e
gene ically and an igenically di e se, sugges ing he need o upda ed accine
an igens. Con en ional inac i a ed accines de i ed om clade 2.3.4.4 i uses a e
unlikely o p o ec agains clade 2.3.2.1a i uses, wa an ing he conside a ion o
mul i alen accines and he e ologous p ime-boos ing app oaches whe e hese
clades co-ci cula e in domes ic bi ds.
The e is a close co ela ion be ween an ibody i e, suscep ibili y o in ec ion, and disease
ou come. When accines a e used, pos - accinal an ibody esponses should be
moni o ed a he a m le el o moni o accine up ake and moun ing o an immune
esponse. I using con en ional inac i a ed accines, locks should be moni o ed egula ly
h oughou he comme cial p oduc ion cycle. Boos e doses should be adminis e ed o
educe he likelihood ha an ibody i es all below le els expec ed o p e en disease.
An ibody i es a e less eliable indica o s o p o ec ion when using ec o ed accines
alone. I is impo an ha i uses de ec ed in accina ed locks a e cha ac e ised and
assessed o he p esence o mu a ions ha migh lead o an igenic changes.
No hing in his epo should be cons ued as an endo semen o a speci ic p oduc , and
he in o ma ion p o ided is gene al in na u e. Addi ional suppo on ele an accines can
be ob ained om FAO, WOAH and OFFLU.
Findings
Clade 2.3.4.4b
An igenic assessmen s using e e ence chicken an ise a om in e na ional pa ne s ha e
shown limi ed a ia ion in he an igenic cha ac e is ics o hese 2023 i uses al hough
he e was some a ia ion by sub ype. This has been no ed in i uses om poul y in
coun ies whe e ci cula ion is p esumed enzoo ic. Tes ed i uses om wild bi ds a e less
an igenically di e se han i uses om poul y. Con inuous ci cula ion in wild bi ds and
ecu en spillo e s in o poul y could u he complica e he an igenic p o iles o i uses
ound in some coun ies. The limi ed a ailabili y o s ains om egions whe e hese
i uses con inue o ci cula e in poul y has cons ained he comp ehensi eness o hese
impa ial assessmen s.
Vaccine e icacy es ing has been conduc ed in se e al Eu opean coun ies as epo ed in
OFFLU AIM pilo epo in a ange o poul y hos s. B ie ly, coo dina ed ials assessed
di e en accine pla o ms (inac i a ed, ec o ed, ecombinan p o ein, and mRNA
accines), h ee domes ic hos species (chicken, u key, and duck) and using di e en
accina ion egimens agains challenge wi h con empo a y clade 2.3.4.4b i uses. The
ials measu ed clinical ou comes, i us shedding, immune esponses and ansmission.
O e all accine selec ion and accina ion egimens used may need modula ing by species
o ensu e a p o ec i e esponse, o example, da a gene a ed om ials on chickens
should no be in e p e ed o in e e icacy o accines in o he species. (EFSA AHAW Panel,
2023). Fo mo e in o ma ion e e o he EFSA publica ion (EFSA AHAW Panel, 2023) ha
summa ises he ial da a which is no ye a ailable in pee - e iewed li e a u e bu ia
some online epo s (Ge me aad e al., 2023; G asland e al., 2023).
In o he accine challenge s udies ca ied ou in Egyp , local clade 2.3.4.4b H5N1 and
H5N8 i uses collec ed in 2022 and 2019 we e used, espec i ely, as challenge i uses
(Hamdy e al., 2024). Th ee di e en inac i a ed accines we e es ed in comme cial
b oile chickens: an H5N1 clade 2.3.2; an H5N1 clade 2.3.4 and an H5N8 clade 2.3.4.4b.
Only he clade 2.3.4.4b accine p o ided clinical p o ec ion agains expe imen al
challenge wi h he clade 2.3.4.4b H5N1 2022 i us 21 days pos -single accina ion. No
in o ma ion was a ailable on i al shedding.
Vaccine challenge s udies ha e been ca ied ou in he USA using a clade 2.3.4.4b No h
Ame ican i us om 2022. One s udy in ol ed b oile chickens o SPF legho ns and used
HVT ec o accines wi h a 2.2 inse and a compu a ionally op imised b oadly eac i e
an igen HVT ec o accine. Lee e al. (2024) epo ed good p o ec ion ollowing challenge
o bo h accines. In ano he s udy in ol ing SPF legho ns, used an inac i a ed gH5N1
clade 2.3.4.4c accine and alpha i us RNA pa icle accine wi h he HA om a No h
Ame ican H5 clade 2.3.4.4b i us om 2022, bo h p o iding 100% p o ec ion and educed
i al shedding (Spackman e al., 2024).
S udies pe o med on wild bi d clade 2.3.4.4b isola es om 2021 in China demons a ed
ha he Re-14 accine an igen (H5N8 clade 2.3.4.4b i us in a PR8 backbone) was a
ele an ma ch o hese i uses and p o ided good p o ec ion in ducks (Tian e al., 2023).
Expe imen al s udies may no e lec he ield si ua ion, and ials wi h chickens may no
be applicable o o he species; howe e , collec i ely he abo e ials demons a e
p o ec ion om disease om es ed accines and educ ion in shedding om pos 2021, o
H5N1 clade 2.3.4.4b i uses.
In some egions, clade 2.3.4.4b i uses coexis wi h o he , an igenically di e en endemic
s ains meaning mul i alen accines may need o be conside ed o ensu e ully p o ec i e
immuni y agains HPAI.
Eu ope
Recen HPAI e en s in Eu ope ha e been desc ibed in de ail elsewhe e (EFSA, 2024).
Vi uses de ec ed in wild bi ds and poul y in Eu ope in 2023 ha e been an igenically
cha ac e ised and demons a ed o be an igenically simila . In Janua y 2024, wo
ou b eaks o HPAI A(H5N1) in accina ed ducks in F ance we e epo ed o WOAH. These
i uses ha e no been an igenically cha ac e ised, howe e he e was no e idence o
onwa ds ansmission no gene ic changes associa ed wi h accine escape. The iming o
in ec ion o hese ducks was consis en wi h ei he ea ly (i.e., no ecei ing ull accina ion
cou se) o waning immuni y om accina ion a he han changes o he an igenici y o he
i us. Vi uses which eme ge in accina ed popula ions, especially i hey con ain gene ic
changes, should be subjec o addi ional cha ac e isa ion as a ma e o impo ance , as
discussed in OFFLU AIM Module 2.
A ica
F om a ailable da a mos i uses de ec ed in poul y in sub-Saha an A ica a e de i ed
om in oduc ions o clade 2.3.4.4b om Eu ope in 2021 howe e some i uses ha e been
de ec ed in wild bi ds om subsequen in oduc ions. Clade 2.3.4.4b i uses sp eading
in o A ica ha e la gely eplaced o he p e iously ci cula ing clade i uses. In No h A ica
endemic clade 2.3.4.4b H5N8 con inues o co-ci cula e alongside H5N1.
An igenic cha ac e iza ion o 18 clade 2.3.4.4b H5N1 i uses, om ou sub-Saha an
A ican coun ies collec ed be ween 2021 and 2023 displayed a simila pa e n o an igenic
eac i i y o o he Eu asian clade 2.3.4.4b i uses, howe e hese i uses a e b oadly
sp ead ac oss he 2.3.4.4b an igenic g oup. Recen (2023) i uses om one A ican coun y
exhibi ed po en ial an igenic d i possibly a e ci cula ing o some ime in poul y;
howe e his could no be a ibu ed o any pa icula amino acid changes. In o ma ion on
an igenic cha ac e is ics o ecen (2023) clade 2.3.4.4b i uses om Egyp is no
a ailable. Enhanced diagnos ic e alua ion and imely elease o global da a is equi ed in
o de o imely unde s and accine equi emen s ac oss much o he A ican con inen .
No h Ame ica
Ou b eaks o a ian in luenza con inue o be epo ed in comme cial poul y and backya d
locks in he USA, al hough a a lowe a e compa ed o las yea . The majo i y o
de ec ions in No h Ame ica a e caused by he H5N1 sub ype howe e he e ha e been
some epo s o H5N5 and H5N6 in wild bi ds (all clade 2.3.4.4b). The e a e no epo s
ega ding he an igenic cha ac e is ics o hese ecen i uses using chicken an ise a, bu
i uses appea o ha e ew mu a ions in known an igenic si es. Less han 1% o i uses
de ec ed in dai y ca le ha e a p edic ed glycosyla ion a si e 156 (H5 numbe ing) which,
when es ed using e e an ise a aised agains a 2.3.4.4b clade i us esul s in a sligh
change in an igenici y compa ed o i uses wi hou his change (WHO, 2024b). This loss in
eac i i y has no been alida ed using chicken se a and his change has no been
obse ed in sequence da a om poul y in No h Ame ica.
Cen al and Sou h Ame ica
A(H5N1) Gs/Gd clade 2.3.4.4b i uses we e i s de ec ed in Cen al and Sou h Ame ica in
la e 2022 and ha e sp ead o he sou he n ip o Sou h Ame ica and onwa d in o
An a c ica. Ou b eaks in his egion ha e had a disp opo iona e impac on he backya d
poul y sec o . Some coun ies ha e decla ed eedom om in ec ion in poul y hough
i uses con inue o ci cula e in wild bi ds. Vi uses om he egion we e in oduced h ough
mul iple wild bi d mo emen e en s in la e 2022 and a e di e ging gene ically om i uses
de ec ed in No h Ame ica in 2022 (Jiminez-Bluhm e al., 2023, Ruiz-Saenz e al., 2023).
Recen isola es om poul y a e no a ailable om coun ies whe e accines ha e been
deployed and i is impo an o con inue o moni o i uses, especially in a eas whe e
accina ion is being used, o ully cha ac e ize hem an igenically. Gene ically
ep esen a i e isola es om wild bi ds in he egion om 2023 we e an igenically
cha ac e ised and clus e ed wi h o he clade 2.3.4.4b i uses howe e some o hese
i uses demons a ed inc easing an igenic dis ances om ea ly clade 2.3.4.4b i uses.
This wa an s close moni o ing and es ing o hese i uses as hey e ol e especially in
a eas o enzoo ic ci cula ion in poul y.
Asia
Clade 2.3.4.4b i uses a e widesp ead ac oss much o Asia and many coun ies ha e
expe ienced mul iple incu sions o i us in oduced in o poul y in 2020 and 2021. Since
Oc obe 2023, H5N1 o mul iple clades plus di e en sub ypes (H5N5, H5N6 and H5N8)
clade 2.3.4.4b i uses ha e been de ec ed in poul y o wild bi ds. The clade 2.3.4.4b
appea s dominan bu he e is s ill no able ci cula ion o o he clade i uses in some
coun ies.
Clade 2.3.4.4b i uses appea s o ha e eplaced o he Gs/Gd clades in China and a simila
end has been obse ed in o he coun ies in Bangladesh and pa s o Sou heas Asia
hough no in o he s. China upda ed accine an igens in ea ly 2022 ollowing he e-
in oduc ion o clade 2.3.4.4b i uses (Shi e al., 2023). H5N1, H5N6 and H5N8 clade
2.3.4.4b i uses isola ed in China in 2021-2022 exhibi ed sub ype-speci ic an igenic
he e ogenei y (Lin e al., 2024) as also epo ed by Soda e al., (2023) using H5N1 and
H5N8 clade 2.3.4.4b i uses isola ed in Japan be ween 2021 and 2022.
Limi ed in o ma ion is a ailable on he an igenic cha ac e is ics o ecen i uses om he
egion, howe e OFFLU AIM es ed clade 2.3.4.4b i uses om wo Asian coun ies om
2023. The H5N1 i uses es ed om Sou h Asia clus e ed an igenically wi h o he Eu asian
H5N1 i uses. The H5N1 i uses es ed om Sou heas Asia a e om a ious in oduc ions
in o Sou heas Asian poul y bu limi ed genomic su eillance da a om his egion means
i is unclea how ep esen a i e hese i al s ains a e. These i uses, al hough clus e ing
wi h o he clade 2.3.4.4b s ains we e no an igenically homogeneous. This highligh s he
impo ance o i al and an igenic moni o ing o he ea ly de ec ion o di e gen e olu ion
especially in a eas o enzoo ic ci cula ion o i us in poul y. Fu he mo e, i highligh s he
impo ance o selec ing s ains ep esen a i e o con empo a y i uses i he decision o
implemen accina ion using an au ogenous inac i a ed accine we e o be aken.
As epo ed in he las AIM epo , in Indonesia he clade 2.3.4.4b i uses we e epo ed o
he i s ime in 2022 in domes ic ducks (Wibawa e al., 2024). These i uses we e
an igenically cha ac e ised agains clade 2.3.2.1
1
, 2.3.2.1c1 s ains which a e used in
accines in Indonesia. Resul s sugges ed ha he 2.3.4.4b i uses we e an igenically
di e en he e o e upda ing wi h new accine candida es which a e an igenically ma ched
o ci cula ing i uses may be equi ed i hese new in oduc ions esul in spillo e o
domes ic bi ds. In his scena io i may equi e he use o bi alen o i alen H5 seed
s ains ac oss mul iple Gs/Gd clades (OFFLU, 2023).
Clade 2.3.4.4h
Mul iple clade 2.3.4.4h i uses we e de ec ed in humans in China in 2024 indica ing he e
may s ill be some ci cula ion o his i us clade in poul y despi e he lack o epo s and
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 .
in equen de ec ion since 2022, ollowing upda e o he poul y accine, o include a mo e
con empo a y 2.3.4.4h an igen. Repo s indica e he e is gene ic di e gence o hese
i uses and accumula ion o amino acid changes compa ed o he 2018 CVV howe e he
signi icance o hese changes is unclea (especially wi h espec o poul y accines),
since no an igenic da a was a ailable a he ime o w i ing (WHO, 2024c). Fu he mo e,
some o he ecen A(H5N6) clade 2.3.4.4h i uses ha e accumula ed o e 15 HA amino
acid subs i u ions ela i e o a ailable CVVs. The ex en o he ci cula ion o his clade is
unknown. I should be no ed ha one clade 2.3.4.4h i us om Sou heas Asia in 2019 was
an igenically cha ac e ised in he ecen AIM p og amme and was no ecognised by
an ise a o clade 2.3.4.4b, 2.3.4, 2.2 no clade 1 i uses and he e o e was no included in
he an igenic maps. I was an igenically di e en o clade 2.3.4.4b i uses. Vaccines
a ge ing clade 2.3.4.4 i uses would be unlikely o p o ide p o ec ion agains o he
an igenically di e en clades.
Clade 2.3.2.1c1
Clade “2.3.2.1c1” i uses ha e gene ically di e si ied since hei eme gence, he e o e in
new p oposed ye unpublished i us nomencla u e, hose which a e cu en ly e e ed o
in-coun y as clade 2.3.2.1c1 ha e been e-designa ed clade 2.3.2.1e/g/c
2
. I is impo an o
acknowledge ha hese di e en ly named clades a e no ela ed o newly eme ging
i uses, bu a he e lec changes and upda ed nomencla u e due o con inuous i al
e olu ion.
One clade 2.3.2.1g2 i us om he Indonesian A chipelago collec ed in 2022 was
an igenically cha ac e ised and was no ecognised by clade 2.3.4.4b, 2.3.4, 2.2 no clade
1 an ise a and hus was no included in he an igenic maps. I was an igenically di e en o
clade 2.3.4.4b i uses. Indonesia has a good sys em in place o upda ing accines when
an igenic a ian s eme ge (Ha aningsih e al., 2015). Vaccines a ge ing clade 2.3.4.4
i uses would be unlikely o p o ide p o ec ion agains clade 2.3.2.1c1 i uses. This clade
will be u he cha ac e ised and add essed by OFFLU in u u e wo k.
One clade 2.3.2.1e2 i us om Sou heas Asia collec ed in 2018 was an igenically
cha ac e ised and was no ecognised by clade 2.3.4.4b, 2.3.4, 2.2 no clade 1 an ise a
and hus was no included in he an igenic maps. I was an igenically di e en o clade
2.3.4.4b i uses. Fu he s udies a e needed on he an igenic cha ac e is ics o ecen
clade “2.3.2.1c1” i uses om Cambodia, Vie Nam and Laos, howe e gene ic in o ma ion
and an igenic cha ac e isa ion using e e an ise a sugges s hese i uses a e di e si ying
2
P o isional nomencla u e was aken om he WHO/FAO/WOAH H5 Nomencla u e Wo king G oup who de ine "clades" using HA gene sequences, and de ine clades
as gene ically dis inc , monophyle ic g oups o i uses. This nomencla u e spli s clade 2.3.4.4 in o eigh addi ional sub-clades, named 2.3.4.4a h ough 2.3.4.4h due o
high ci cula ing di e si y wi hin he clade and. well as subclades 2.3.2.1a h ough 2.3.2.1g o he 2.3.2.1 spli .
and may be somewha an igenically a iable, bu a e mos ly ecognised by clade 2.3.2.1
se a (WHO, 2024a). Tes s should be ca ied ou on hese i uses o ensu e poul y accine
ma ch, a p io i y o OFFLU AIM’s nex epo . Inac i a ed accines based on clade 2.3.4.4b
would no be expec ed o p o ide consis en p o ec ion agains clade 2.3.2.1c1 i uses.
Clade 2.3.2.1a
Vi uses o he clade 2.3.2.1a ha e been ci cula ing since 2011 and con inue o be de ec ed
in poul y in some coun ies in Sou h Asia despi e incu sions o clade 2.3.4.4b i uses in o
poul y (Islam e al., 2024). Xing e al., (2024) concluded ha he clade 2.3.2.1d RE-12
inac i a ed accine p o ided he bes p o ec ion agains disease in chickens o p e-2019
clade 2.3.2.1 i uses de ec ed in China, howe e he i uses de ec ed ecen ly in Sou h
Asia a e conside ably gene ically di e gen om es s ains in he s udy. Du a e al.,
(2024) epo ed he de ec ion o clade 2.3.2.1a in chickens and ducks in asymp oma ic
accina ed backya d poul y in Bangladesh in 2017, howe e Kwon e al., (2021) ound
accines in use (clade 2.3.2.1a and clade 2.2) s ill o e ed p o ec ion agains disease,
despi e some an igenic a ia ion in clade 2.3.2.1a i uses de ec ed in 2017. In he WHO
Feb ua y 2024 epo on he gene ic and an igenic cha ac e is ics o zoono ic in luenza A
i uses (WHO 2024a), wo an igenic g oups o 2.3.2.1a i uses we e desc ibed, using e e
an ise a, de ined by he amino acid p esen a posi ion 154 (H5 numbe ing). Vi uses es ed
in OFFLU AIM a e hough o be gene ically ep esen a i e o con empo a y ci cula ing
i uses, despi e he ela i ely limi ed genomic da a a ailable. Vi uses es ed om 2023
demons a ed an igenic a iabili y. Compa ed o i uses es ed om p e ious yea s, he
an igenic dis ance be ween es i uses and an ise a aised agains su oga e i uses o
accine seed s ains had inc eased. This indica es ha a subse o hese i uses
ci cula ing in he Sou h Asian egion a e d i ing an igenically and u he s udies a e
equi ed o assess accine e icacy agains con empo a y clade 2.3.2.1a i uses o ensu e
ha p o ec ion agains disease can be p o ided by accines which a e cu en ly in use.
This should include analysis o se a om ield accina ed bi ds agains a panel o
con empo a y clade 2.3.2.1a an igens. Conside a ion should be gi en o he need o
upda e an igens o con en ional inac i a ed accines which a e in ended o p o ide
p o ec ion agains clade 2.3.2.1a i uses.
Con en ional inac i a ed accines de i ed om clade 2.3.4.4 i uses would likely no
p o ide app op ia e p o ec ion agains clade 2.3.2.1a i uses based on he la ge an igenic
di e ences be ween hese clades, he e o e when mul iple clade i uses ( o example
clade 2.3.2.1a and clade 2.3.4.4b) a e known o be ci cula ing, he use o mul i- alen
accines should be conside ed.
Yang J, Zhang C, Yuan Y, Sun J, Lu L, Sun H, Sun H, Chu D, Qin S, Chen J, Zhang C, Hao X,
Shi W, Liu W, Gao GF, Diga d P, Lyce S, Bi Y. No el A ian In luenza Vi us (H5N1) Clade
2.3.4.4b Reasso an s in Mig a o y Bi ds, China. Eme g In ec Dis. 2023 Jun;29(6):1244-
1249. doi: 10.3201/eid2906.221723.
Yong ao Ye, Ma cus Shum, Joseph Tsui, Guangchuang Yu, Da id Smi h, Huachen Zhu,
Joseph Wu, Yi Guan, Tommy Tsan-Yuk Lam. Robus expansion o phylogeny o as -
g owing genome sequence da a. bioRxi 2021.12.30.474610