Editorial
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The current state of vaccines used in
the field for foot and mouth disease
virus in China
Expert Rev. Vaccines 10(1), 13–15 (2011)
Zhiyong Li
Author for correspondence:
State Key Laboratory of
Veterinary Etiological Biology,
Key Laboratory of Grazing
Animal Diseases of Ministry
of Agriculture, Lanzhou
Veterinary Research Institute,
Chinese Academy of
Agriculture Sciences,
1 Xujiaping, Lanzhou,
730046 China
Tel.: +86 931 834 2685
Fax: +86 931 834 0977
li_zhiyong56@yahoo.com.cn
Jixing Liu
State Key Laboratory of
Veterinary Etiological Biology,
Key Laboratory of Animal
Virology of Ministry of
Agriculture, Lanzhou
Veterinary Research Institute,
Chinese Academy of
Agriculture Sciences,
1 Xujiaping, Lanzhou,
730046 China
www.expert-reviews.com 10.1586/ERV.10.146
“Foot and mouth disease is the most important disease of the
Office International des Epizooties list A due to its effect on trade.
The highly infectious nature of the disease, combined with its
ability to cause persistent infections and to exist as multiple types
and variants, makes foot and mouth disease difficult to control.”
Foot and mouth disease (FMD) is the disease, combined with its ability to cause
highly contagious disease of livestock that persistent infections and to exist as multiple
causes severe economic loss in susceptible types and variants, makes FMD difficult to
cloven-hoofed animals such as cattle, swine, control [4] . The Chinese government under-
sheep and goats. FMD virus (FMDV) is a took vaccination of livestock by preventive
member of genus Aphthovirus of the fam- vaccination programs, supplemented by the
ily Picornaviridae. Seven immuno­logically slaughter of infected animals and susceptible
distinct serotypes (A, O, C, Asia 1, SAT I, in-contact animals. The types of FMDV
SAT II and SAT  III) have been identi- vaccines that have been developed in China
fied  [1] . Viral infection or immuniza- include: inactivated vaccine; synthesized
tion with one serotype does not confer peptide vaccine; recombinant adenovirus,
protection against the other serotypes [2] . pseudorabies or fowlpox-vectored vaccine;
In recent years, three serotypes of FMDV empty capsid-like particles produced from
have caused epidemics in China. In March recombinant baculoviruses; DNA vaccines;
2005, FMDV serotype Asia 1 was found and oral vaccine produced from transgenic
in Hong Kong. Subsequently, this type of plants [5–12] . Among these, the inactivated
the virus was reported in mainland China vaccine and synthesized peptide vaccine are
in April 2005 [3] . In 2009, type A FMDV currently available for use in government-
caused outbreaks of FMD in cattle in approved disease control programs in China,
Wuhan, Hubei Province, Shanghai and and the vaccine composed of inactivated
Beijing. In early 2010, a type O FMDV antigen and empty capsid-like particles pro-
outbreak was recorded in Shenzhen, duced from recombinant silkworm baculo-
Guangzhou Province. So far, outbreaks of virus are used in eight provinces and autono-
FMD O have been reported in several prov- mous regions of China. Other vaccines are
inces and autonomous regions of China, still under evaluation in the laboratory or
which suggests that the virus might have field to establish their safety and efficacy.
crossed China.
Foot and mouth disease is the most impor- Inactivated vaccine
tant disease of the Office International des The inactivated vaccine is produced by
Epizooties (OIE) list A due to its effect on infecting baby hamster kidney (BHK)-21
trade. The highly infectious nature of the cells with virulent FMDV, followed by
Keywords : China • empty capsid vaccine • foot and mouth disease virus • inactivated vaccine
• safety • synthesized peptide vaccine • vaccination
© 2011 Expert Reviews Ltd ISSN 1476-0584 13
 Editorial Li & Liu
inactivation with binary ethyleneimine (BEI) and purification by
ultrafiltration [13] . The vaccines can be monovalent or multivalent,
including viruses of different serotypes of FMDV. Only monova-
lent/multivalent vaccines for type O, type A and type Asia 1 are now
produced and used in China. All companies in China producing
FMDV-inactivated vaccines do so under strict biosecure conditions.
Problems
Although the inactivated vaccine has been shown to be effective, it
may lead to new outbreaks of FMD, either because of the incom-
plete inactivation of FMDV in large-scale production or owing to
the escape of the live virus from vaccine plants. It has been proven
that the virus involved in FMD outbreaks was sometimes closely
related to virus strains used in vaccine manufacturing plants. The
FMD outbreak in the UK in 2007 was caused by an FMDV 01
BFS67-like virus that only existed in FMD reference laboratories
and pharmaceutical manufacturing plants. In addition, the FMDV
circulating in China in 2005 was genetically closely related to an
Indian FMDV vaccine strain [14] . In addition to the aforemen-
tioned disadvantage, the vaccine may also contain varying degrees
of contaminating viral nonstructural proteins (NSPs), depending
on the manufacturer. Currently, the diagnostic tests to distinguish
virus-infected carrier animals from vaccinated animals are based
on the detection of antibodies to viral NSPs. As a result, it is dif-
ficult to distinguish between vaccinated and field-infected animals
by currently approved diagnostic tests [15] .
Synthesized peptide vaccine
The FMDV (type O) synthesized peptide vaccine for swine has been
used in the field in China since 2007. Now the synthesized peptide
vaccine’s market share is close to that of the inactivated vaccine.
The synthetic peptide vaccine has been designed with the B-cell
sites spans the entire G–H loop domain and extensive flank-
ing sequences, has a unique consensus sequence to confront the
hypervariability of serotype O viruses and a promiscuous artificial
Th site. It has shown good immunogenicity in swine but limited
immunogenicity in cattle.
Problems
The synthesized peptide vaccine reduces the risk of outbreak from
laboratories or vaccine-manufacturing plants because it does not
use the virus in its manufacturing process. �����������������
Although the syn-
thesized peptide vaccine is safer than the inactivated vaccine, it
has several potential disadvantages. First, some of the antigenic
sites on FMDV are discontinuous and involve different regions
of a capsid protein or more than one protein. Therefore, only a
limited number of antigenic sites and T-cell epitopes of FMDV
can be synthesized and consequently the vaccine is not able to
induce significant protection. Second, the quasispecies nature of
FMDV invites the selection of antigenic variants not targeted by
the vaccine that could cause outbreaks in animals vaccinated with
peptide vaccines [16] . Of note, the outbreak of type O FMDV
seen in China in 2010 coincided with the widespread use of the
synthesized peptide vaccine in the field. This interesting finding
requires further investigation.
14
Type O & Asia-1 bivalent vaccine (empty capsid
vaccine compound)
The type O and Asia 1 bivalent vaccine (empty capsid vaccine
compound) is composed of type O inactivated antigens and type
Asia 1 empty capsid-like particles produced from recombinant
silkworm baculoviruses. It was licensed for use in eight provinces
and autonomous regions of China in 2008. The company produc-
ing the vaccines follows the guidelines of the Veterinary Bureau
at the Ministry of Agriculture for Veterinary Medicines Products.
Clinical, immunological and virological data documenting the
efficacy of these vaccines are required by the Veterinary Bureau at
the Ministry of Agriculture.
“The complete control and eradication of foot and
mouth disease virus can only ultimately be achieved
by a combination of vaccination, extensive
surveillance and an effective monitoring program.”
Compared with synthetic peptide vaccines, the empty capsid
vaccine contains the entire repertoire of antigenic sites present
on the 140S virion, thereby decreasing the possible selection of
antigenic variants from the quasispecies. Empty viral capsids are
as immunogenic as the 140S virions; however, they are noninfec-
tious as they lack nucleic acid. The safety is thus improved and
the empty capsid vaccine is considered safer than the inactivated
vaccine [17] .
The type O and Asia 1 bivalent vaccine (empty capsid vaccine
compound) consists not only of the pure empty capsid-like
������������������
parti-
cle component but also includes the type O inactivated antigen.
However, the production of type  O inactivated antigens still
requires the use of live virus in the manufacturing process. This
means that the safety of the compound vaccine is lower than that
of the pure empty capsid vaccine. It is the authors’ opinion that
this compound vaccine needs to be replaced by pure empty capsid
vaccine. However, the empty capsid-like particles of type O are
more difficult to obtain by genetic engineering techniques as the
viral capsid of type O is more acid-sensitive than other types of
FMDV [18] .
Conclusion
The vaccine is a fundamental component of strategies aimed at
China’s control and eradication of FMD. The inactivated vac-
cine remains the most widely used FMD vaccine in the world.
However, some measures need to be strengthened to ensure the
quality and safety of the vaccine. First, a greater emphasis should
be placed on quality assurance/quality control in order to reduce
the risk of spreading viruses from manufacturing plants. Second,
the FMD inactivated vaccine should be purified by industrial
ultrafiltration and chromatography in order to remove unwanted
cellular protein contaminants and viral NSP. As a new-gener-
ation vaccine, the synthesized peptide vaccine is safer than the
inactivated vaccine, but whether the synthesized peptide vac-
cine could overcome the quasispecies problem still needs to be
evaluated. The type O and Asia 1 bivalent vaccine (empty capsid
vaccine compound) should be evaluated in the field based on
Expert Rev. Vaccines 10(1), (2011)
 Vaccines for foot & mouth disease virus in China Editorial

clinical, immunological and virological data. After successful
assembly of the empty capsids of type O FMDV, the compound
vaccine should be replaced by pure empty capsid vaccine. It is the
authors’ opinion that the empty capsid vaccine should be used
predominately in China’s FMD control policy in the future and
that the empty capsid vaccine would also be greatly beneficial to
control outbreaks of FMD in disease-free countries. Although
the control strategies that include culling FMD-infected animals
and susceptible animals, but not vaccination, allow the countries
to resume FMD-free status quickly, it is not economical and
ethical to implement mass slaughter of healthy animals. After
the outbreak in UK in 2001, some reports recommended the
development of both improved vaccines and modern diagnostic
methods to control FMD [19] . According to this recommenda-
tion, we believe the empty capsid vaccine would be greatly ben-
eficial to control outbreaks of FMD in disease-free countries.
As the empty capsid vaccine lacks infectious viral nucleic acid,
the FMD disease-free countries do not need to worry about
the escape of infectious virus. In addition, the animals vacci-
nated with the empty capsid vaccine can be distinguished from
infected or convalescent carrier using currently approved diag-
nostic assays. In addition to the aforementioned vaccines, new-
generation efficacious vaccines, such as virus-vectored vaccine,
should be developed. Moreover, research concerning appropriate
adjutants for vaccines to induce either a Th1 or a Th2 response
is also required.
The vaccination strategy has been effective and has played an
important role in the control of FMDV infection in China. Despite
the successes obtained with the vaccination strategy, China still
faces challenges in its efforts to eliminate FMDV circulation in
livestock. The complete control and eradication of FMDV can
only ultimately be achieved by a combination of vaccination,
extensive surveillance and an effective monitoring program.
Acknowledgement
The authors would like to thank Lauren Constable at Expert Reviews Ltd
for her helpful comments.
Financial & competing interests disclosure
This work was supported by grants from National 863 Project of China
(No. 2006AA02Z440) and Chinese Funding for Social Public Interests
(No. 2005DIB4J041). The authors have no other relevant affiliations or
financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials discussed
in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

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