Vital elements for the successful control of foot-and-mouth disease by vaccination

doi:10.1016/S0264-410X(98)00443-5

Vaccine

Volume 17, Issues 13–14, January 1999, Pages 1760-1766

https://doi.org/10.1016/S0264-410X(98)00443-5 Get rights and content

Abstract

The efficient control of foot-and-mouth disease (FMD) by immunisation depends not only on the appropriate choice of vaccine in terms of innocuity, potency and strain composition, but also on a series of inter-related zoo-sanitary factors which are equally important. These include: national, centralised planning (including contingency planning) and control; vaccination and revaccination policy; the availability of epizootiological intelligence based on adequate diagnostic capability and ongoing immunological surveillance; the logistics of supply with its components of storage, transport and distribution; proper vaccine application; cleaning and disinfection of premises, vehicles and personnel; identification of individual animals; control of animal movement; recording; ongoing economic outcome and benefit analyses; training and retraining of professional and technical staff; public relations and especially the commitment of the agricultural community. These elements are reviewed in this paper.

Introduction

In the 70 years which have elapsed since the first publications appeared on vaccination against foot-and-mouth disease (FMD)[1], major advances have been made in virtually all aspects of our understanding of the virus, the disease and the methods for its control. Studies in areas including: the molecular biology of the virus; the pathogenesis of the disease; the excretion, dissemination and persistence of the virus; the epidemiology of the disease; the immune response; the genetic and antigenic relationships between strains of virus and the reliable production of safe and potent vaccines[2]have all provided information which has been applied in increasingly effective approaches to the control of FMD. Nevertheless, and despite spectacular success in many countries where the disease was formerly endemic, large areas of the globe continue to suffer the depredations of FMD. The reasons for these failures are complex, but insufficient attention to basic elements of planning and resource in the prosecution of control schemes can be critically important.

Section snippets

Centralised planning and control

While control schemes for FMD may be aimed initially at the local reduction of infection, of disease severity and of disease incidence and prevalence, the ultimate aim should be the total eradication of the disease. In endemic areas the approach taken will vary according to local circumstances. However, the ultimate goal is inevitably attained in stages. Thus the disease and measures for its control progress from endemicity at the initiation of mass vaccination, moving through increasing

Epizootiological intelligence and diagnosis

Comprehensive and up-to-date epizootiological information is a prerequisite for effective disease control. Within a country or region, information on the status of a particular disease can be gathered by veterinarians, in both the private and public sectors, and even earlier and more effectively by an educated livestock community. In the case of FMD the notification procedure is usually reinforced by the designation of the disease in national legislation as being compulsorily notifiable on the

Diagnostic laboratory capability

Many countries maintain virological laboratories equipped for the diagnosis of FMD and the serological surveillance for both the disease and the immune status of herds and flocks in which vaccination has been applied.

Much of this work can today be effected without the necessity to employ live virus by the use of inactivated viruses and non-infectious viral components. This approach is to be commended. However, it is to be noted that where the work involves material which is known, or suspected,

Selection of FMD vaccine

There are currently a number of commercially manufactured vaccines available of differing strain composition, antigenic content, adjuvant formulation and cost[2]. All are produced using inactivated antigens. Vaccine is available as fully formulated and tested product or, more usually in emergency situations, it can be freshly formulated from concentrated, inactivated antigen(s) stored at low temperature in vaccine banks maintained by commercial manufacturers or by national and international

The cold chain

FMD vaccines must be maintained under refrigeration for the optimal retention of antigenic potency, usually at 4±2°C. The antigen loses immunogenic activity progressively as the storage temperature increases above these levels[26]. In addition freezing and thawing of FMD vaccines damages their integrity and can also cause the breakage of both aluminium hydroxide gels and oil emulsions, decreasing and possibly destroying the immunogenicity of the vaccines. The efficiency of the cold chain is

Training and education

Veterinarians, animal technicians and vaccinators should be educated, trained and tested to appropriate levels in good vaccination practice, good hygienic practice, disease control and legislation. Plans, contingency plans and SOPs are valuable aids in this area. Topics to be covered may include:

•
The disease and its effects.
•
The care of vaccine and vaccination equipment, including the sterilisation of syringes and needles.
•
Vaccine application (site(s) of inoculation, dose rates for different

Logistics of supply and distribution

Ideally vaccine will be ordered with the maximum remaining shelf life and in quantities appropriate to a given phase of the vaccination campaign. The aim should be to attain at least 80% and preferably 100% vaccine coverage of susceptible livestock. Lesser levels of coverage and the use of vaccines of poor potency are likely to be associated with inefficient control and, importantly, with the selection of antigenic mutants in partially immune animal populations. It is to be recognised, however,

Public relations

The commitment of the farming community to schemes of animal disease control can greatly facilitate success. Conversely, the lack of their commitment renders the task much more difficult. This is particularly evident when there is an element of cost to the farmer. For these reasons it is important to use all available means to publicise control measures for FMD and to explain the rationale, the legal requirements, the timetable and the benefits which are expected to accrue from their

Conclusions

Despite the complexity of FMD in terms of the multiplicity of types and strains, the wide host range and the highly contagious nature of the disease, vaccination campaigns combined with other zoo-sanitary control measures have been attended with notable success in many parts of the world. A conspicuous example is found in continental Europe where mass compulsory vaccination together with the control of the movement of live animals and of animal products, sometimes combined with the slaughter

Acknowledgements

I thank Dr. A.I. Donaldson for his critical review of the manuscript.

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Broad immunogenic spectrum of monovalent and trivalent foot-and-mouth disease virus vaccines containing O<inf>1</inf> campos, A24 cruzeiro and A Argentina 2001 strains against circulating viral lineages in cattle and pigs
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FMD remains endemic in many Asian and African countries where multiple variants of serotypes O and A, among others, currently circulate. Due to lack of cross-protection between serotypes and incomplete protection between some strains even within a serotype, an important challenge for the application of effective vaccination programs is to select highly immunogenic and widely cross-reactive vaccine strains. Adaptation of a candidate field virus for use as a vaccine can be quite complex, so that whenever possible, the use of well-established vaccine viruses could have enormous advantages. FMD vaccine strains harmonized for use in South America have shown excellent results in FMD control, not only in the region, where it is still used systematically as a preventive measure, but also more recently in some Asian countries. To gain further insight into the immunogenic spectrum of these strains, VN tests (VNT) were performed with sera from cattle and/or pigs vaccinated with monovalent (type O) or trivalent (types O and A) formulations against 122 type O and 32 type A field viruses isolated from 35 countries in Asia and Africa, belonging to different lineages. Almost all VNT titers obtained were within the expected protective level, indicating the wide immunogenic spectrum of high potency FMD vaccines formulated with O₁ Campos, A24 Cruzeiro and A Argentina 2001 South American vaccine strains belonging to EURO-SA topotypes against currently active viruses from other topotypes. These in vitro results are in line with previously reported in vivo challenge tests in pigs against three A/ASIA/Sea-97 isolates and two isolates belonging to type O lineages O/SEA/Mya-98 and O/ME-SA/Ind-2001e.
Efficacy of a high quality O<inf>1</inf>/Campos foot-and-mouth disease vaccine upon challenge with a heterologous Korean O Mya98 lineage virus in pigs
2018, Vaccine
Citation Excerpt :
Infection or vaccination with one serotype does not cross-protect against the other serotypes and may fail to protect fully against some strains within serotypes [5,6]. Inactivated vaccines are widely used to control, eradicate and prevent FMD [7,8]. Historically, serotype O vaccine strains can be included within two main groups.
In 2010 serotype O foot-and-mouth disease virus of the Mya98 lineage/SEA topotype spread into most East Asian countries. During 2010–2011 it was responsible for major outbreaks in the Republic of Korea where a monovalent O/Manisa vaccine (belonging to the ME-SA topotype) was applied to help control the outbreaks. Subsequently, all susceptible animals were vaccinated every 6 months with a vaccine containing the O/Manisa antigen. Despite vaccination, the disease re-occurred in 2014 and afterwards almost annually. This study focuses on the in vivo efficacy in pigs of a high quality monovalent commercial O₁/Campos vaccine against heterologous challenge with a representative 2015 isolate from the Jincheon Province of the Republic of Korea. Initially, viral characterizations and r₁ determinations were performed on six viruses recovered in that region during 2014–2015, centering on their relationship with the well characterized and widely available O₁/Campos vaccine strain. Genetic and antigenic analysis indicated a close similarity among 2014–2015 Korean isolates and with the previous 2010 virus, with distinct differences with the O₁/Campos strain. Virus neutralisation tests using O₁/Campos cattle and pig post vaccination sera and recent Korean outbreak viruses predicted acceptable cross-protection after a single vaccination, as indicated by r₁ values, and in pigs, by expectancy of protection. In agreement with the in vitro estimates, in vivo challenge with a selected field isolate indicated that O₁/Campos primo vaccinated pigs were protected, resulting in a PD50 value of nearly 10. The results indicated that good quality oil vaccines containing the O₁/Campos strain can successfully be used against isolates belonging to the O Mya98/SEA topotype.
Emergence of antigenic variants of Foot-and-Mouth Disease Virus serotype O in Ecuador and preliminary evaluation of a field strain as a vaccine candidate
2014, Vaccine
Citation Excerpt :
Infection or vaccination with one serotype does not cross-protect against other serotypes and may also fail to protect fully against other strains of the same serotype [5,6]. Inactivated vaccines are widely used to control, eradicate and prevent FMD [7,8]. Selection of vaccine strains that are as immunogenic and cross reactive as possible is essential not only for systematic vaccination programs but also for the incorporation to strategic FMDV inactivated frozen antigens for rapid formulation into vaccines for use in case of an emergency (i.e. antigen banks) [9].
Foot-and-Mouth Disease Virus serotype O has been circulating regularly throughout most provinces of Ecuador, one of the two South American countries that still remain endemic, although satisfactory vaccination coverage was reported. This study concentrates in the characterization of isolates collected during 2008–2011, focusing particularly on the antigenic and immunogenic relationships of the field viruses with the O₁/Campos vaccine strain in use in the region and with an experimental vaccine formulated with a representative strain of the 2010 epidemic. The results established that antigenically divergent variants poorly protected by the vaccine in use emerged and co-circulated in a limited period of time. A monovalent vaccine formulated with the representative 2010 strain elicited high antibody titers and protected against challenge with homologous virus. In addition, cross-reactive antibodies to predominant viruses in the region were established. In overall this study indicates the ability of the virus to diversify under field conditions in which a vaccine strain with poor match is applied, and the potential of the selected 2010 field virus as a vaccine candidate for incorporation into strategic antigen banks and/or for addition to current formulations for systematic vaccination, in order to prevent the emergence of even more divergent isolates in the future.
Characterization of a type O foot-and-mouth disease virus re-emerging in the year 2011 in free areas of the Southern Cone of South America and cross-protection studies with the vaccine strain in use in the region
2013, Veterinary Microbiology
Citation Excerpt :
Serotypes O, A and C have been recorded in South America. Vaccination is widely applied to control, eradicate and prevent FMD (Garland, 1999; Bergmann et al., 2005). Moreover, a considerable transformation is ongoing regarding the acceptance of the benefits of vaccination as an alternative to stamping out policies, particularly after recurrence of the disease in free regions (Bergmann et al., 2005).
Molecular, antigenic and vaccine matching studies, including protective response in vivo, were conducted with a foot-and-mouth disease type O virus isolated during the outbreak in September 2011 in San Pedro, Paraguay, country internationally recognized as free with vaccination in 1997. The phylogenetic tree derived from complete VP₁ sequences as well as monoclonal antibody profiling indicated that this isolate was related to viruses responsible for previous emergencies in free areas of the Southern Cone of South America occurring sporadically between the years 2000 and 2006. Marked differences with the vaccine strain O₁/Campos, including the loss of reactivity with neutralizing MAbs, were recognized. Levels of protective antibodies induced by the vaccine containing the O₁/Campos strain against the San Pedro virus and the virus responsible for the previous emergency in 2006 in the Southern Cone assessed by in vitro vaccine matching studies pointed to an insufficient protective response 30 days after vaccination (DPV), which was properly attained at 79 DPV or after revaccination. In agreement with the in vitro assessment, the in vivo challenge in the Protection against Podal Generalization test in cattle indicated appropriate protection for the San Pedro strain at 79 DPV or after revaccination. The complementary conclusions that can be derived from vaccine matching tests designed differently to fit the various objectives intended: prophylaxis, emergency vaccination or incorporation of new field strains into antigen banks, is evaluated. This is the first report of the antigenic and immunogenic characterization of the variants responsible for emergencies in the Southern Cone of South America and the putative impact of the changes on the cross protection conferred by the vaccine strain.
Characterization of foot-and-mouth disease virus from outbreaks in Ecuador during 2009-2010 and cross-protection studies with the vaccine strain in use in the region
2011, Vaccine
Citation Excerpt :
The disease has an important socio-economic impact in countries where it is endemic [10,11], provokes huge economic consequences when outbreaks occur in disease free regions [12,13] and is considered one of the most important constrains to international trade of livestock and animal products. Vaccination is widely used to control, eradicate and prevent FMD [14,15]. Moreover, a considerable transformation is ongoing regarding the acceptance of the benefits of vaccination as an alternative to stamping out policies, particularly after recurrence of the disease in free regions [15].
During the years 2009 and 2010 relevant epidemic waves of foot-and-mouth disease (FMD) serotype O occurred in Ecuador, representing a great drawback for the last stages of the ongoing eradication program in South America. This study describes the molecular and antigenic characterizations of 29 isolates collected from various regions in the country and their relationship to the vaccine strain. The phylogenetic tree derived from sequences spanning the complete VP₁ protein showed that, despite the widespread origin of the viruses, they were all related among themselves and to previous isolates occurring in 2008, with around 10% difference with the vaccine strain O1/Campos. The high level of sequence conservation among different isolates in the various regions of Ecuador pointed to a common origin, suggesting animal movements as possible sources of viral spread. Monoclonal antibody profiling grouped the isolates in two major reactivity patterns which differed from that of the vaccine strain. Both profiles showed loss of reactivity with the same four MAbs, three of them with neutralizing properties. Additional sites were lost in the profile representing most of the 2010s viral samples. Levels of protective antibodies induced by the vaccine against the field strains assessed by in vitro vaccine matching studies also pointed to an increased temporal pattern of loss of a protective response. Moreover, results obtained with in vivo challenge in the protection against podal generalization test in cattle, clearly indicated lack of appropriate protection of the Ecuadorian field strains by the vaccine virus in use, which in the case of a 2010 variant was observed even after revaccination.
A review of the effectiveness of vaccine potency control testing
2003, International Journal for Parasitology
The use of potency control testing is a valuable tool for testing the actual relative strength of manufactured assembly lots of vaccine. Biological-based manufacturing methods are inherently variable and potency testing is a tool to ensure lot-to-lot consistency of commercial vaccines. A strong historical link to clinical efficacy has been established where correlation to efficacy and adequate test validation have been achieved. The link to immunogenicity and efficacy has traditionally been strongest with attenuated vaccines and toxoids. Control potency test failure does predict that a serial or batch of vaccine would most likely provide insufficient immunogenicity in typical field applications. Because of the complexity of pathogenic processes and associated immune responses, potency tests may not always directly predict the effectiveness of a vaccine. Thus, vaccines that pass control potency testing may not always provide adequate efficacy. This is particularly true of adjuvanted, inactivated vaccines. In the development of vaccine formulations and control tests for vaccines, the nature of the desired protective immune responses to the targeted pathogen (when known) should be considered. These considerations could provide better alternatives in the assays chosen as correlates of immunity and may more accurately predict efficacy and assure batch-to-batch consistency. Also, the effects of the dose and duration of antigen exposure as well as the nature of antigen presentation and generation of extrinsic cytokines could be characterised and correlated to vaccine potency as additional indicators of vaccine efficacy.

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Vital elements for the successful control of foot-and-mouth disease by vaccination

Abstract

Introduction

Section snippets

Centralised planning and control

Epizootiological intelligence and diagnosis

Diagnostic laboratory capability

Selection of FMD vaccine

The cold chain

Training and education

Logistics of supply and distribution

Public relations

Conclusions

Acknowledgements

J. Comp. Pathol. Ther.

Vet. J.

Vet. Microbiol.

J. Infect. Dis.

Natural and vaccine-induced immunity to foot-and-mouth disease: the prospects for improved vaccines

Rev. Sci. Tech. Off. Int. Epiz.

Risk analysis in practice: a foot-and-mouth disease control strategy for the European Community

Rev. Sci. Tech. Off. Int. Epiz.