http://www.who.int/wer/2007/wer8219/en/index.html
Antigenic and genetic characteristics
of H5N1 viruses and candidate
H5N1 vaccine viruses developed
for potential use as pre-pandemic
vaccines, March 2007
The development of representative pre-pandemic H5N1
candidate vaccine viruses by the WHO Global Infl uenza
Programme 1 is being conducted as 1 component of the
overall global strategy for pandemic preparedness. This
summary provides an update on the characterization of
H5N1 viruses circulating in birds, those that have caused
human infections and the development of candidate
H5N1 vaccine viruses. National authorities may use this
information to guide decision-making about producing
pre-pandemic vaccines.
The H5N1 viruses chosen previously for development
as pre-pandemic candidate vaccine viruses were
representative of antigenically and genetically distinct
groups of viruses that infected humans primarily
through contact with H5N1-infected birds that were ill
or dead. These representative candidate vaccine viruses
were prepared using reverse genetics; they were tested for
safety prior to release for production of pilot vaccine lots,
which may be used in experimental studies and in some
instances for stockpiling by governments in advance of a
possible H5N1 pandemic.
It is recommended that manufacturers consult individual
national authorities to determine the specifi c H5N1
viruses to be used in preparing experimental pilot
lots and stockpiles. Decisions should be based on the
epidemiology and geographical distribution of the
circulating H5N1 viruses described below.
Comparisons are ongoing of the candidate H5N1 vaccine
viruses developed from clade 1 and clade 2 viruses with
respect to immunogenicity and cross-reactivity, and their
relationship to newly emerging H5N1 viruses; these will
be reported by WHO periodically.
Genetic characteristics of recent H5N1 viruses
The haemagglutinin (HA) sequences of the majority
of H5N1 viruses circulating in avian species during
the past 4 years separate into 2 distinct phylogenetic
clades (or genetic groups). 2 Clade 1 viruses circulating
in Cambodia, Thailand and Viet Nam were responsible
for human infections in those countries during 2004
and 2005, and in Thailand during 2006. Clade 2 viruses
have circulated in birds in China and Indonesia since
2003; they spread westwards during 2005 and 2006 to
the Middle East, Europe and Africa. Since late 2005, clade
2 viruses have been principally responsible for human
infections. Multiple subclades of clade 2 have been
distinguished; 3 of these ? subclades 1, 2 and 3 (Fig. 1)
etc....
Antigenic and genetic characteristics
of H5N1 viruses and candidate
H5N1 vaccine viruses developed
for potential use as pre-pandemic
vaccines, March 2007
The development of representative pre-pandemic H5N1
candidate vaccine viruses by the WHO Global Infl uenza
Programme 1 is being conducted as 1 component of the
overall global strategy for pandemic preparedness. This
summary provides an update on the characterization of
H5N1 viruses circulating in birds, those that have caused
human infections and the development of candidate
H5N1 vaccine viruses. National authorities may use this
information to guide decision-making about producing
pre-pandemic vaccines.
The H5N1 viruses chosen previously for development
as pre-pandemic candidate vaccine viruses were
representative of antigenically and genetically distinct
groups of viruses that infected humans primarily
through contact with H5N1-infected birds that were ill
or dead. These representative candidate vaccine viruses
were prepared using reverse genetics; they were tested for
safety prior to release for production of pilot vaccine lots,
which may be used in experimental studies and in some
instances for stockpiling by governments in advance of a
possible H5N1 pandemic.
It is recommended that manufacturers consult individual
national authorities to determine the specifi c H5N1
viruses to be used in preparing experimental pilot
lots and stockpiles. Decisions should be based on the
epidemiology and geographical distribution of the
circulating H5N1 viruses described below.
Comparisons are ongoing of the candidate H5N1 vaccine
viruses developed from clade 1 and clade 2 viruses with
respect to immunogenicity and cross-reactivity, and their
relationship to newly emerging H5N1 viruses; these will
be reported by WHO periodically.
Genetic characteristics of recent H5N1 viruses
The haemagglutinin (HA) sequences of the majority
of H5N1 viruses circulating in avian species during
the past 4 years separate into 2 distinct phylogenetic
clades (or genetic groups). 2 Clade 1 viruses circulating
in Cambodia, Thailand and Viet Nam were responsible
for human infections in those countries during 2004
and 2005, and in Thailand during 2006. Clade 2 viruses
have circulated in birds in China and Indonesia since
2003; they spread westwards during 2005 and 2006 to
the Middle East, Europe and Africa. Since late 2005, clade
2 viruses have been principally responsible for human
infections. Multiple subclades of clade 2 have been
distinguished; 3 of these ? subclades 1, 2 and 3 (Fig. 1)
etc....