A Review of OIE Country Status Recovery Using Vaccinate-to-Live Versus Vaccinate-to-Die Foot-and-Mouth Disease Response Policies I: Benefits of Higher Potency Vaccines and Associated NSP DIVA Test Systems in Post-Outbreak Surveillance.

To rapidly return to trade, countries with OIE status, FMD-free country where vaccination is not practised, have destroyed emergency vaccinated animals, raising ethical concerns with respect to social values, the environment, animal welfare and global food security. This two-part review explores whether science could support eligibility to return to previous OIE status in 3 months irrespective of vaccinate-to-live or vaccinate-to-die policies. Here, we examine the benefits of higher potency (≥ 6 PD50 ), high-purity vaccines formulated from antigen banks for emergency use, their efficacy and performance in differentiating infected from vaccinated animals (DIVA) assays for post-outbreak surveillance. From an intensive programme of research, we conclude that high-quality, higher potency vaccines are proven to reduce FMD virus (FMDV) subclinical circulation and the risk of carriers. Broader coverage than predicted by serology suggests the potential to hold a few 'key' vaccine strains improving logistics and reducing the financial burden of antigen banks. The OIE should adopt formal definitions for emergency vaccination and emergency vaccines. In terms of supportive tools, we consider that the lack of OIE recognition of DIVA tests other than those of PANAFTOSA in cattle is a shortcoming. There is need for research on maternal antibody interference with DIVA tests and on the use of such tests to establish whether greater purification of vaccines improves performance. We consider that alignment of waiting periods for vaccinate-to-live and vaccinate-to-die in OIE Code Article 8.5.9 1 b. and c. is feasible until an acceptable level of statistical certainty for surveillance or target probability of freedom is established to substantiate the absence of FMDV infection or circulation. It is surveillance intensity rather than waiting periods that establishes the risk of residual FMDV. EU Directive 2003/85/EC implicitly recognizes this, permitting derogation of the OIE waiting periods.

A Review of OIE Country Status Recovery Using Vaccinate-to-Live Versus Vaccinate-to-Die Foot-and-Mouth Disease Response Policies II: Waiting Periods After Emergency Vaccination in FMD Free Countries.

For countries with OIE status, FMD free country where vaccination is not practised, vaccinate-to-live policies have a significant economic disincentive as the trade restriction waiting period is double that of vaccinate-to-die policies. The disposal of healthy vaccinated animals strictly for the purpose of regaining markets with debatable scientific justification is a global concern. The feasibility of aligning the waiting periods to facilitate vaccinate-to-live is explored. The first article of this two-part review (Barnett et al., 2015) explored the qualities of higher potency Foot-and-Mouth Disease (FMD) vaccines, performance of differentiating infected from vaccinated animals (DIVA) diagnostic assays particularly in vaccinates and carriers, as well as aspects of current limitations of post-outbreak surveillance. Here, the history behind the OIE waiting periods for FMD free status is reviewed as well as whether the risk of vaccinated animals and their subsequent products differ appreciably at 3 versus 6 months. It is concluded that alignment is feasible for vaccinate-to-live using higher potency FMD vaccines within the current OIE waiting period framework of 3 and 6 months blocks of time. These waiting periods reflect precedence, historical practicalities and considered expert opinion rather than a specific scientific rationale. The future lies in updated epidemiological and diagnostic technology to establish an acceptable level of statistical certainty for surveillance or target probability of freedom of FMDV (infection or circulation) not time restricted waiting periods. The OIE Terrestrial Code limits trade from a FMD free country where vaccination is not practiced to animal products and live non-vaccinated animals. The risk of FMDV in products derived from higher potency vaccinated animals is appreciably less than for countries with infected FMD status or even from a FMD free country where vaccination is practised for which the Code has Articles with guidelines for safe trade with time restrictions of 3 months or less. All these presume that key requirements in the implementation of emergency vaccination including appropriate vaccine match, vaccine application, susceptible population coverage, etc. are addressed.

A DNA vaccination regime including protein boost and electroporation protects cattle against foot-and-mouth disease.

Protection against foot-and-mouth disease (FMD) using DNA technology has been documented for sheep and pigs but not for the highly susceptible species of cattle. Twenty-five Holstein Friesian cross-bred cattle were vaccinated twice, 21 days apart, with a DNA vaccine containing the capsid coding region (P1) along with the non-structural proteins 2A, 3C and 3D (pcDNA3.1/P1-2A3C3D) of O(1) Kaufbeuren alone or coated onto PLG (d,l-lactide-co-glycolide) microparticles. In some pcDNA3.1/P1-2A3C3D was also combined with an adjuvant plasmid expressing bovine granulocyte macrophage colony stimulating factor (GM-CSF). DNA vaccinations were administered intramuscularly with, or without, the use of electroporation and at 42 days post primary vaccination cattle received a protein boost of 146S FMD virus (FMDV) antigen and non-structural protein 3D. For comparison, four cattle were vaccinated with a conventional FMD vaccine and two more included as unvaccinated controls. Apart from those immunised with PLG microparticles all cattle were challenged with 10(5) TCID(50) cattle adapted O(1) Lausanne FMDV virus at day 93 post primary vaccination. All DNA vaccinated cattle regardless of regime developed good humoral and cell mediated responses prior to challenge. The best overall virus neutralising antibody, IFN-γ and clinical protection (75%) were seen in the cattle whereby the DNA was delivered by electroporation. In contrast, only 25% of cattle vaccinated with the DNA vaccine without electroporation were clinically protected. The addition of GM-CSF in combination with electroporation further improved the efficacy of the vaccine, as demonstrated from the reduction of clinical disease and virus excretions in nasal swabs. We thus demonstrate for the first time that cattle can be clinically protected against FMDV challenge following a DNA prime-protein boost strategy, and particularly when DNA vaccine is combined with GM-CSF and delivered by electroporation.

Foot-and-mouth disease marker vaccine: cattle protection with a partial VP1 G-H loop deleted virus antigen.

Contrary to the dogma that the VP1 G-H loop is essential for FMD vaccine efficacy, it has been previously shown that foot-and-mouth disease 146s antigen containing heterologous VP1 G-H loops confers complete protection in pigs and cattle. Moreover, serological evaluation of cattle vaccinated with an antigen lacking a large proportion of the VP1 G-H loop indicated that these animals should be protected against infection with FMD. Absence of this loop provides opportunity for the development of an FMD negative marker vaccine, allowing infection to be detected by antibodies against this missing region. Cattle vaccinated with this negative marker vaccine were fully protected following virus challenge 28 days post vaccination as determined by the absence of generalised lesions on their feet. Furthermore, use of our improved differentiation ELISA identified animals exposed to infection as early as 7 days post-challenge. We thus demonstrate, for the first time, the ability of this FMD negative marker vaccine to fully protect cattle from experimental challenge and rapidly distinguish animals that are subsequently exposed to infection.

Characterisation and epitope mapping of neutralising monoclonal antibodies to A24 Cruzeiro strain of FMDV.

Characterisation of seven neutralising monoclonal antibodies (mAbs) produced against foot-and-mouth disease virus A(24) Cruzeiro revealed three reactivity groups. Gr-I recognised linear epitopes where as Gr-II was conformation-dependent and trypsin-insensitive. The Gr-III was also conformation-dependent, but trypsin-sensitive. Mar (mAb neutralisation resistant)-mutants could only be produced against Gr-I and Gr-III mAbs. Capsid sequence comparison of Gr-I mar-mutants with parent virus revealed changes in the G-H loop of VP1 at positions 141, 143 and 147. Similarly, a Gr-III mar-mutant showed a change from a highly conserved glycine to a tryptophan at position 148 of VP1 along with three additional changes at the N-terminus of VP1, VP2 and VP4. This residue at 148 of VP1 is located at +2 position after "RGD" and is equivalent to the position identified by the mAb recognising site 5 in serotype O viruses. This site is probably formed because of the interaction of the G-H loop with other residues in different structural proteins.

Marker vaccine potential of a foot-and-mouth disease virus with a partial VP1 G-H loop deletion.

Previous work in cattle and pigs demonstrated that protection against foot-and-mouth disease (FMD) could be achieved following vaccination with chimeric foot-and-mouth disease virus (FMDV) vaccines, in which the VP1 G-H loop had been substituted with that from another serotype. This indicated that the VP1 G-H loop may not be essential for the protection of natural hosts against FMDV. If this could be substantiated there would be potential to develop FMD marker vaccines, characterised by the absence of this region. Here, we investigate the serological responses to vaccination with a virus with a partial VP1 G-H loop deletion in order to determine the likelihood of achieving protection and the potential of this virus as a marker vaccine. Inactivated, oil adjuvanted, vaccines, consisting of chemically inactivated virus with or without a partially deleted VP1 G-H loop, were used to immunise cattle. Serum was collected on days 0, 7, 14 and 21 and antibody titres calculated using the virus neutralisation test (VNT) to estimate the likelihood of protection. We predict a good likelihood that cattle vaccinated with a vaccine characterised by a partial VP1 G-H loop would be protected against challenge with the same virus containing the VP1 G-H loop. We also present evidence on the potential of such a construct to act as a marker vaccine, when used in conjunction with a novel serological test.

Toward a global foot and mouth disease vaccine bank network.

A network of foot and mouth (FMD) vaccine banks has been initiated with the support of vaccine bank managers and technical advisors that participated in a workshop held at the Institute for Animal Health, Pirbright, in the United Kingdom in April 2006. Terms of Reference that provide guidance for coordinated activities are under consultation. Practical and economic benefits can be realised from collaboration, which will be achieved through mutually acceptable mechanisms for the exchange of information and materials relevant to vaccine banks and their management. If administrative and technical hurdles can be overcome, the network has the potential to contribute significantly to the improved control of FMD worldwide. A 'global' and interactive vaccine bank association could be created by agreeing a system of resource sharing that could orchestrate additional emergency cover with vaccine or antigen from the reserves of network members.

The importance of quality assurance/quality control of diagnostics to increase the confidence in global foot-and-mouth disease control.

The last decade international trade in animals and animal products was liberated and confidence in this global trade can increase only if appropriate control measures are applied. As foot-and-mouth disease (FMD) diagnostics will play an essential role in this respect, the Food and Agriculture Organization European Commission for the Control of Foot-and-Mouth Disease (EUFMD) co-ordinates, in collaboration with the European Commission, several programmes to increase the quality of FMD diagnostics. A quality assurance (QA) system is deemed essential for laboratories involved in certifying absence of FMDV or antibodies against the virus. Therefore, laboratories are encouraged to validate their diagnostic tests fully and to install a continuous quality control (QC) monitoring system. Knowledge of performance characteristics of diagnostics is essential to interpret results correctly and to calculate sample rates in regional surveillance campaigns. Different aspects of QA/QC of classical and new FMD virological and serological diagnostics are discussed in respect to the EU FMD directive (2003/85/EC). We recommended accepting trade certificates only from laboratories participating in international proficiency testing on a regular basis.

FMD vaccines: reflections on quality aspects for applicability in European disease control policy.

Most foot-and-mouth disease (FMD) vaccines used around the world are inactivated vaccines for prophylactic or emergency use, generally manufactured by the same basic methodology outlined in the OIE Manual and, for Europe, in the European Pharmacopoeia, and for the EU Member States in compliance with Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products as amended by Directive 2004/28/EC. Most of the requirements that apply to all immunological veterinary medicinal products apply equally to FMD vaccines. There are, however, some unique features of the disease and vaccines used against it that require a different approach to fulfil the requirements of the relevant legislation, if a vaccinate-to-live policy will be applied with 'authorized' vaccines. Several aspects of vaccine efficacy and safety are elaborated with emphasis on quality assurance/quality control (QA/QC). The purity of the vaccine in respect of the presence of non-structural protein antibodies could be checked indirectly by serology after vaccination. The viability of a vaccine bank approach was greatly aided by the principle of storing inactivated concentrated FMD viral antigen (Ag) over liquid nitrogen for subsequent formulation into vaccine. A worldwide Ag bank network might be an option for the far future and a solution to the problem of covering many different FMDV serotypes and strains. The producers should respect the strict FMD biosecurity rules worked out by the FAO EUFMD and described in Council Directive 2003/85/EC. Making the experience related to vaccine QA/QC available to all countries will reduce the risk of an FMD outbreak within these countries and consequently will reduce the FMD risk around the world.

Chimeric foot-and-mouth disease viruses: evaluation of their efficacy as potential marker vaccines in cattle.

Previous work in pigs, has demonstrated that full protection against foot-and-mouth disease (FMD) can be achieved following vaccination with chimeric foot-and-mouth disease virus (FMDV) vaccines, in which the VP1 G-H loop had been substituted with that from another serotype. If proven to be effective in other economically important species such as cattle, such vaccine constructs could be trialed as potential marker vaccines. Here, we determine if G-H loop chimera FMDV vaccines can: (i) protect cattle from virus challenge and (ii) induce an antibody response that would enable the identification of infection, regardless of vaccination status. Inactivated, oil adjuvanated, chimeric vaccine constructs, based on the backbone sequence of the A(12)119 serotype virus, fully protected cattle from challenge 21 days post-vaccination. Differentiation assays developed for use in this study were able to identify sub-clinical infection, which in one vaccinated animal, persisted beyond day 32 post-challenge. This paper emphasises the importance of epitopes outside of the VP1 G-H loop for protective immunity in cattle, and demonstrates that chimeric FMDV vaccines could prove to be useful marker vaccines for the future.

Evaluation of a monoclonal antibody-based approach for the selection of foot-and-mouth disease (FMD) vaccine strains.

Foot-and-mouth disease (FMD) virus exists as seven serotypes within which are numerous variants necessitating careful selection of vaccine strains. Currently, a serological assay system based on the use of polyclonal vaccine antisera is widely used for this selection. However, inherent variability in the matching antisera used makes the tests poorly reproducible and difficult to interpret. In this study, we have explored the possibility of replacing or supplementing the polyclonal antibody (PAb)-based method with one based on use of monoclonal antibodies (MAb). Panels of MAbs raised against two serotype O vaccine strains were examined for reactivity with 22 field viruses, isolated over a 10-year period between 1991 and 2001. Antigenic site 2 was found to comprise more than one epitope. The sequence variation in capsid protein VP2 harbouring antigenic site 2 was analysed and the amino acid residues at positions 79 and 134 appeared to greatly influence the binding of site 2 MAbs. Prediction of antigenic match based on MAb reactivity did not correlate closely with the results of a PAb-based "gold-standard" method and it was concluded that a wider panel of MAbs are needed that recognise all protective epitopes present on the surface of FMD virus together with a better understanding of those epitopes which are important in conferring protection.

Porcine gammadelta T cells: possible roles on the innate and adaptive immune responses following virus infection.

gammadelta T cells recognise different types of antigen in alternative ways to alphabeta T cells, and thus appear to play a complementary role in the immune response. However, unlike alphabeta T cells, the role or function of gammadelta T cells is still unclear. As pigs possess a high proportion of circulating gammadelta T cells, they are suitable large animal model to study gammadelta T cell functions. This as yet has not been fully exploited, leaving porcine gammadelta T cell biology and its role in immunity in its infancy. Foot-and-mouth disease (FMD) high potency "emergency" vaccines are able to induce early protection from challenge and it has been suggested that, in part, there is some involvement of innate immune responses. The antigen component of the vaccine is able to stimulate purified naive pig gammadelta T cells and induce the mRNA of various cytokines and chemokines. This observation suggests that gammadelta T cells probably contribute to the early phase of the immune responses to FMD vaccination, and perhaps infection. A subset of these circulating gammadelta T cells display a phenotype similar to professional antigen presenting cells and are able to take up and present soluble antigen to CD4(+) T cells in a direct cell-cell interaction via MHC class II. This direct interaction between gammadelta T cells and CD4(+) T cells is likely to have a significant influence on the out come of the adaptive immune response.

Effect of emergency FMD vaccine antigen payload on protection, sub-clinical infection and persistence following direct contact challenge of cattle.

Previous work, in sheep vaccinated with emergency foot-and-mouth disease (FMD) vaccine, indicated the benefit of increasing the antigen payload in inhibiting local virus replication and consequently persistence following an indirect aerosol challenge with a virus homologous to the vaccine strain. The work presented here investigates this possibility further using cattle and a more severe semi-heterologous direct contact challenge. The quantitative dynamics of virus replication and excretion in both vaccinated and non-vaccinated cattle following challenge are examined. Two experiments were carried out each involving 20 vaccinated and 5 non-vaccinated cattle. An O(1) Manisa vaccine (18 PD(50)) was used for the first, previously reported experiment [Cox SJ, Voyce C, Parida S, Reid SM, Hamblin PA, Paton DJ, et al. Protection against direct contact challenge following emergency FMD vaccination of cattle and the effect on virus excretion from the oropharynx. Vaccine 2005;23:1106-13]. The same vaccine was used for the second experiment described in this paper except the antigen payload was increased 10-fold per bovine dose, resulting in significantly higher FMD virus neutralising antibody titres prior to challenge. Twenty-one days post-vaccination the cattle received a 5-day direct contact challenge with FMD virus from five further non-vaccinated cattle infected 24h earlier with O UKG 34/2001. All vaccinated cattle regardless of antigen payload were protected against clinical disease. Sub-clinical oropharyngeal infection was detected in animals from both experiments but the level of virus replication shortly after direct contact challenge was significantly reduced in vaccinated animals. Cattle immunised with the 10-fold antigen payload cleared the virus more readily and consequently at 28 days post-challenge fewer animals were persistently infected compared to the single strength vaccine. Following a severe challenge, the results from both experiments show that use of emergency vaccine can prevent or decrease local virus replication and thereby dramatically reduce the amount of virus released into the environment, particularly during the early post-exposure period. Additionally, increasing the antigen payload of the vaccine may reduce sub-clinical infection, leading to fewer persistently infected virus carrier animals.

Interferon-gamma production in vitro from whole blood of foot-and-mouth disease virus (FMDV) vaccinated and infected cattle after incubation with inactivated FMDV.

Studies were performed to determine whether a rapid method to detect cell mediated immune responses to foot-and-mouth disease virus (FMDV) could be used either as a diagnostic test or provide a correlate of protection in animals post-vaccination. Using protocols based on the BOVIGAM assay for tuberculosis, whole blood samples from FMDV vaccinated or control animals, before and after challenge infection, were stimulated overnight with inactivated FMDV antigen. The quantity of interferon gamma (IFN-gamma) produced in the supernatants was measured using an ELISA. Specific induction of IFN-gamma was detected in samples from vaccinated, infected and vaccinated-then-infected cattle. Further development of this assay may provide a useful tool for the diagnosis of FMDV immune animals, including the identification of vaccinated animals that have been subsequently infected with FMDV. In these studies, combining the results of the IFN-gamma assay with virus neutralising antibody titre, in groups of vaccinated animals, provided a correlation with the capacity to control virus replication after subsequent challenge.

The application of new techniques to the improved detection of persistently infected cattle after vaccination and contact exposure to foot-and-mouth disease.

Detection of antibodies to the non-structural proteins (NSP) of foot-and-mouth disease virus (FMDV) was compared with conventional serological and virological methods and with RT-PCR for the identification of FMDV carrier animals obtained after experimental contact challenge of vaccinated cattle. Transmission from carriers to sentinels was also monitored. Twenty FMDV vaccinated and five unvaccinated cattle were challenged by direct contact with five donor cattle excreting FMDV and monitored until 28 days post challenge-exposure . Twelve vaccinated and three unvaccinated animals were retained up to 24 weeks post exposure to FMDV in order to monitor viral persistence, transmission and antibody responses. In nine vaccinated animals, infection persisted beyond 28 days post exposure, virus being detected more frequently and for longer in oesophagopharyngeal samples from these animals when examined by RT-PCR rather than by virus isolation. Although recovery of FMDV RNA became increasingly sporadic over time, the number of RNA copies detected in positive samples declined only slowly. Two naïve sentinel cattle housed with the persistently infected animals between 93 and 168 days after the latter had been challenge-exposed to FMDV did not become infected. There were differences in the ability of commercially available serological tests to detect antibodies to FMDV non-structural proteins (NSP) in vaccinated and subsequently challenged cattle. Although no single test could identify all of the vaccinated cattle that became persistently infected, the most poorly recognised animals were those with the least evidence of virus replication based on other tests. The potential of the detection of antibodies to the 2B NSP of FMDV for diagnosing persistent FMDV infection was demonstrated.

Detection of antibody to the foot-and-mouth disease virus (FMDV) non-structural polyprotein 3ABC in sheep by ELISA.

The specificity and sensitivity of an ELISA for detecting IgG to the 3ABC non-structural protein of foot-and-mouth disease (FMD) virus was evaluated in FMD naive, aerosol-infected, aerosol plus direct contact infected and field-exposed sheep. All 12 sheep that were experimentally infected without prior vaccination seroconverted in the test, although fewer field sera from FMD-exposed sheep were scored seropositive compared to test results for structural protein antibodies. The 3ABC test specificity was 98 or 100% according to whether sera reacting in the doubtful range were scored as positive or negative. The test was then used to investigate the antibody response of sheep vaccinated against FMD and exposed to the virus by an aerosol challenge 4-14 days later. The response of individual animals varied. Whether immunised with high or low doses of vaccine, the development of 3ABC antibody was most likely in sheep from which live virus was recovered at or beyond 9 days post-challenge. Non-structural responses were also more frequent in animals from which multiple incidences of live FMD virus isolation (perhaps more indicative of true virus replication) were demonstrated.

Protection against direct-contact challenge following emergency FMD vaccination of cattle and the effect on virus excretion from the oropharynx.

The ability of emergency foot-and-mouth disease (FMD) vaccine to protect cattle from a heterologous direct-contact challenge and the effect on virus excretion from the oropharynx were examined. An oil adjuvant O1 Manisa FMD vaccine protected 20 cattle from clinical disease following 5 days of direct-contact exposure to five infected cattle at 21 days post vaccination. The donor cattle had been infected by tongue inoculation with a different FMD virus of the same serotype (O UKG 2001). Protection from clinical disease did not prevent localised sub-clinical infection at the oropharynx in most animals, although quantitative reverse transcriptase polymerase chain reaction (RT-PCR) showed that the level of virus replication shortly after direct-contact challenge was greatly reduced in vaccinated animals. Nevertheless, 45% of the vaccinated cattle became persistently infected with 10(3)-10(6) RNA copies per millilitre of oropharyngeal fluid at 28 days post challenge. However, since live virus could not be readily isolated, the risk of these animals transmitting disease was probably very low. The findings show that even after an extremely severe challenge, use of an emergency vaccine will prevent or reduce local virus replication and thereby dramatically reduce the amount of virus released into the environment in the all-important early post-exposure period. These data should help to model the dynamics of virus transmission in future outbreaks of disease where vaccination is considered.

Evidence that high potency foot-and-mouth disease vaccine inhibits local virus replication and prevents the "carrier" state in sheep.

The ability of a single administration of a high, medium and low potency foot-and-mouth disease (FMD) vaccine to decrease or inhibit local virus replication and excretion in the oropharynx of sheep following aerosol challenge with homologous live virus 14 days later was examined. Unvaccinated sheep showed signs of clinical FMD, whereas all of the vaccinated sheep, regardless of antigen payload, were protected against clinical disease and development of viraemia. Virological and serological results confirmed that there had been no local virus replication in the oropharynx of sheep from the high potency vaccine group in contrast to moderate or substantial virus replication in the oropharynx of the low potency vaccinated or unvaccinated sheep respectively. The vaccines showed no evidence of promoting a local mucosal antibody response at the time of virus challenge, but were capable of stimulating a systemic gamma interferon response, the level of which was related to the antigen payload. This suggests that the systemic gamma interferon response could be a useful indicator of the ability of a FMD vaccine to elicit a sterile immunity and indicates that further work is warranted to investigate the role of systemic gamma interferon in this immunity. This is the first experiment to clearly show that high potency, high payload, FMD vaccines are capable of inhibiting local virus replication and consequently persistence and the carrier state in this target species.

Longevity of antibody and cytokine responses following vaccination with high potency emergency FMD vaccines.

The ability of high potency emergency foot-and-mouth disease (FMD) vaccines to promote sustainable immune responses in sheep and pigs following a single application was examined. All vaccine formulations induced a rapid seroconversion in both species, as expected, which was maintained at near peak titres for up to 6 months in sheep and 7 months in pigs. The Montanide ISA 206 formulation gave the best results in sheep. Vaccinated pigs challenged with homologous FMDV were protected from disease at 7 months post vaccination. Systemic levels of cytokines IL-6, IL-8, and in some pigs IL-12, increased following vaccination and were often maintained at an increased level for the duration of the trials. These initial results suggest that high potency vaccines may promote longer lasting immunity than the conventional lower potency vaccines in ruminants and a comparable response in pigs. Results indicate that in an outbreak situation, should emergency vaccination be done with these high potency vaccines, protection should be conferred for a long enough period for the outbreak to be brought under control without the need to revaccinate. Given the increased interval for re-vaccination the use of high potency vaccines for routine prophylactic campaigns could provide a more cost-effective and efficient means of maintaining herd immunity and is an area thus worthy of further examination.

Innate immune responses following emergency vaccination against foot-and-mouth disease virus in pigs.

Inactivated "emergency" foot-and-mouth disease virus (FMDV) vaccine of high potency will induce early protection against the disease, implying a critical role for innate immune defences. At 3 and 6 days post-vaccination (dpv), there was no evidence of vaccine-induced specific anti-FMDV antibodies (Abs), nor enhanced uptake and destruction of opsonised virus by macrophages. Sera from vaccinates and control animals showed similar capacity to neutralise the virus, and were not different from the pre-vaccination sera. There were also no distinguishable changes in the distribution of the different peripheral blood leucocyte (PBL) subpopulations. Nor was any vaccine-induced increase in production of acute phase proteins noted. In contrast, chemotaxis assays identified an increase in PBL migratory activity which was vaccine-related. Furthermore, sera from 3 days post-vaccination contained elevated chemotactic potential. These results demonstrate that enhanced chemotaxis of cells of the innate immune defences, could play an important role during the early protection induced by emergency FMDV vaccines.