Efficacy of intradermally administrated E2 subunit vaccines in reducing horizontal transmission of classical swine fever virus

To investigate if intradermal (ID) vaccination and intramuscular (IM) vaccination result in a comparable reduction of horizontal transmission of classical swine fever virus (CSFV), two registered E2 subunit marker vaccines were examined. Vaccine A was a water-in-oil emulsion containing the E2 glycoprotein originating from the Alfort/Tübingen strain and vaccine B was a water-oil-water emulsion containing the E2 glycoprotein originating from the Brescia strain. Eight groups, of ten pigs each, were vaccinated with either vaccine A or B, intramuscularly (IM) or intradermally (ID). Two different vaccination-challenge intervals were used for each vaccine. Furthermore, one group was vaccinated with a tenfold ID dose of vaccine A and one non-vaccinated group served as a control group. Five pigs from each group were challenged with the moderately virulent CSFV strain Paderborn, while the remaining five pigs served as contacts. Using vaccine A, full transmission to all contact pigs in both ID vaccinated groups occurred. No virus transmission was observed when IM vaccinated pigs were challenged 14 days post-vaccination (14dpv) whereas only one out of five contact pig became infected when they were challenged 10dpv. Using vaccine B no virus transmission was observed when pigs were ID or IM vaccinated and challenged 10dpv. When challenged 3dpv full transmission occurred in the ID vaccinated group, whereas four out of five contact pigs became infected in the IM vaccinated group. This result indicates that ID vaccination does not result in better protection against horizontal CSFV transmission compared to IM vaccination, for the vaccines studied.     

A Malaysia 97 monovalent foot-and-mouth disease vaccine (>6PD50/dose) protects pigs against challenge with a variant FMDV A SEA-97 lineage virus, 4 and 7 days post vaccination

Pigs play a significant role during outbreaks of foot-and-mouth disease (FMD) due to their ability to amplify the virus. It is therefore essential to determine what role vaccination could play to prevent clinical disease and lower virus excretion into the environment. In this study we investigated the efficacy of the double oil emulsion A Malaysia 97 vaccine (>6PD₅₀/dose) against heterologous challenge with an isolate belonging to the A SEA-97 lineage at 4 and 7 days post vaccination (dpv). In addition, we determined whether physical separation of pigs in the same room could prevent virus transmission. Statistically there was no difference in the level of protection offered by 4 and 7 dpv. However, no clinical disease or viral RNA was detected in the blood of pigs challenged 4 dpv, although three of the pigs had antibodies to the non-structural proteins (NSPs), indicating viral replication. Viral RNA was also detected in nasal and saliva swabs, but on very few occasions. Two of the pigs vaccinated seven days prior to challenge had vesicles distal from the injection site, but on the inoculated foot, and two pigs had viral RNA detected in the blood. One pig sero-converted to the NSPs. In contrast, all unvaccinated and inoculated pigs had evidence of infection. No infection occurred in any of the susceptible pigs in the same room, but separated from the infected pigs, indicating that strict biosecurity measures were sufficient under these experimental conditions to prevent virus transmission. However, viral RNA was detected in the nasal swabs of one group of pigs, but apparently not at sufficient levels to cause clinical disease. Vaccination led to a significant decrease in viral RNA in vaccinated pigs compared to unvaccinated and infected pigs, even with this heterologous challenge, and could therefore be considered as a control option during outbreaks.     

Emergency vaccination of sheep against foot-and-mouth disease: significance and detection of subsequent sub-clinical infection

This study has quantified the level of foot-and-mouth disease virus (FMDV) replication and shedding in vaccinated sheep and correlated this to the severity of clinical signs, the induction of antibodies against FMDV non-structural proteins (NSPs) and the transmission of virus to in-contact vaccinated sentinel sheep. To mimic an emergency vaccination regime in the field, sheep were vaccinated with O(1) Manisa vaccine and 4 or 10 days later were indirectly challenged with aerosols from O(1) UKG FMDV infected pigs. Vaccinated and control unvaccinated sheep were monitored for a minimum of 39 days post-challenge. The vaccinated sheep became sub-clinically infected, with reduced virus replication and excretion compared to unvaccinated and clinically infected sheep. Seroconversion to NSP was weak and transient in sheep in which virus replication was of low level and short duration. Virus transmission from vaccinated sub-clinically infected sheep to introduced vaccinated sentinels was not sufficient to cause NSP seroconversion or significant virus shedding. 10% of 10 days and 20% of 4 days vaccinated sheep were virus carriers at greater than 28 days post-challenge compared to 37.5% in the unvaccinated and clinically infected sheep. These results suggest that the low levels of virus replication likely if an effective vaccine is administered at least 4 days prior to challenge exposure are unlikely to result in the spread of infection even under intensive management conditions. Although it may be difficult to detect this infection by serosurveillance, the significance of missing it is likely to be low and the main value of such testing will be to detect undisclosed clinical infection resulting from lack of observation or from exposure to virus before or very soon after vaccination or from vaccine failure due to maladministration or inappropriate strain selection.     

Protective effects of high-potency FMDV O1 Manisa monovalent vaccine in cattle challenged with FMDV O/SKR/2010 at 7 or 4 days post vaccination

Serotype O foot-and-mouth disease (FMD) virus belonging to the SEA topotype continues to be a significant problem in the Eastern Asia region, with outbreaks in Japan and South Korea resulting in the culling of over 3.5 million cattle and pigs in recent years. High-potency O1 Manisa vaccine was previously shown to provide protection in cattle 21 days post vaccination (dpv) following challenge with a representative virus, O/SKR/2010. This study tested the ability of the O1 Manisa vaccine to protect cattle from infection and disease with the O/SKR/2010 virus within just 4 or 7 days post vaccination. The vaccine protected 50% of cattle from clinical disease when administered 7 days prior to challenge, but was not protective with just 4 days between vaccination and challenge. Viraemia was significantly reduced in animals challenged 7 dpv but not 4 dpv, compared to unvaccinated controls, however, there were no effects on the level of virus detected in nasal and oral secretions regardless of vaccination time. The level of neutralising antibodies detected in cattle challenged 7 dpv correlated with protection from clinical disease. All animals seroconverted to FMDV non-structural proteins, suggesting no sterile protection. An equal number of animals became persistently infected in both vaccine groups. The results indicated that high-potency O1 Manisa vaccine administered just 7 days prior to challenge should provide partial protection of cattle if an outbreak of O/SKR/2010, or related viruses, occurs, and would be useful to limit spread of FMDV when used in conjunction with other control measures.     

Serological and mucosal immune responses after vaccination and infection with FMDV in pigs

The aim of this study was to determine a possible correlation between humoral immune responses shortly after vaccination and protection against foot-and-mouth disease virus (FMDV) infection and to study the serological and mucosal antibody responses after vaccination and infection. We used three groups of ten pigs, one non-vaccinated group, one group vaccinated with a single dose vaccine and one group vaccinated with a four-fold dose vaccine. At 7 days post vaccination, five pigs per group were challenged intra-dermally with FMDV O TAW 3/97 and the remaining pigs of each group were contact-exposed to the inoculated pigs. In each group, virus excretion and number of contact infections were quantified. The serological and mucosal antibody responses were evaluated until 116 days post infection. Vaccination resulted in a significant decrease of virus excretion. Stepwise linear regression analysis of variables from individual vaccinated pigs revealed the virus excretion after challenge to be correlated with neutralising antibody titres at the day of challenge (p<0.01). In serum and OPF samples comparable isotype-specific antibody responses (IgM, IgG and IgA), could be detected after vaccination as well as after infection. Remarkably, the pigs with the highest IgA responses after vaccination were protected against contact exposure. After infection, a long lasting (up to 116dpi) IgA response was seen in the non-vaccinated and to a lesser extent in the single dose vaccinated pigs. The induction of NSP antibodies in the vaccinated pigs after infection was lower and of shorter duration as compared to the non-vaccinated infected pigs. This experiment shows that vaccination can reduce virus excretion in pigs, which will contribute to reduced transmission of FMDV in the field, even if the pigs are not fully protected. Moreover, vaccines that induce local IgA responses may be more effective, which merits further investigation.     

Early protection in sheep against intratypic heterologous challenge with serotype O foot-and-mouth disease virus using high-potency,emergency vaccine

In 2009–2011, spread of a serotype O foot-and-mouth disease virus (FMDV) belonging to the South East Asia topotype led to the culling of over 3.5 million cattle and pigs in Japan and Korea. The O1 Manisa vaccine (belonging to the Middle East-South Asian topotype) was used at high potency in Korea to limit the expansion of the outbreak. However, no data are available on the spread of this virus or the efficacy of the O1 Manisa vaccine against this virus in sheep. In this study, the early protection afforded with a high potency (>6 PD₅₀) FMD O1 Manisa vaccine against challenge with the O/SKR/2010 virus was tested in sheep. Sheep (n = 8) were vaccinated 4 days prior to continuous direct-contact challenge with donor sheep. Donor sheep were infected with FMDV O/SKR/2010 by coronary band inoculation 24 h prior to contact with the vaccinated animals, or unvaccinated controls (n = 4). Three of the four control sheep became infected, two clinically. All eight O1 Manisa vaccinated sheep were protected from clinical disease. None had detectable antibodies to FMDV non-structural proteins (3ABC), no virus was isolated from nasal swabs, saliva or oro-pharyngeal fluid and none became carriers. Using this model of challenge, sheep were protected against infection as early as 4 days post vaccination.     

Chimeric (marker) C-strain viruses induce clinical protection against virulent classical swine fever virus (CSFV) and reduce transmission of CSFV between vaccinated pigs

Two live recombinant vaccines (Flc9 and Flc11) against classical swine fever (CSF) were evaluated for their capacity to reduce transmission of virulent CSF virus (CSFV) among vaccinated pigs. In Flc9 the 5' terminal half of the E2 gene of the C-strain, a CSFV vaccine strain, was exchanged with the homologous gene of the bovine viral diarrhoea virus (BVDV) strain 5250, the E(rns) gene was exchanged likewise in the chimeric Flc11 virus. Both recombinant vaccines induce an antibody response in pigs that can be distinguished from that induced after a wild-type CSFV infection. Four experiments were performed to estimate the reproduction ratio R after different vaccination-challenge intervals. Each group consisted of ten pigs [specified pathogen free (SPF) pigs or conventional pigs] that were vaccinated once, intramuscularly, either with Flc9 or Flc11 virus or that were not vaccinated. Vaccinated and susceptible pigs were challenged intranasally with the virulent CSFV strain Brescia or Behring, 1, 2 or 4 weeks after vaccination. Whether contact-pigs became infected was determined using a CSFV specific E2 (Flc9) or E(rns) (FLc11) antibody ELISA. In the unvaccinated control groups, virus secretion started from day 2 to 4 after inoculation and all contact pigs became infected. Contact pigs became infected in the group of pigs (SPF or conventional) vaccinated once with Flc9 virus and challenged 1-, 2- or 4-weeks later. The estimates of the R in the groups challenged at 1-, 2- and 4-weeks after vaccination were 0.38, 0 and 0.75, respectively. Contact infected pigs were not detected (R=0) in any of the groups of pigs, vaccinated with Flc11, only SPF pigs were used. In order to achieve a statistical significance of R within the vaccinated groups each of the experiments has to be repeated at least once. The R of pigs vaccinated with Flc11 virus and challenged at 1- or 2-weeks after vaccination was however significantly lower that the reproduction ratio of the unvaccinated groups (P=0.013). The R of pigs vaccinated with Flc9 virus and challenged at 1 (conventional pigs) or 2 weeks (SPF pigs) after vaccination was significantly lower that the reproduction ratio of the unvaccinated groups (P=0.013). In conclusion, both chimeric viruses Flc9 and Flc11 provided good clinical protection against a challenge with virulent CSFV at 1 or 2 weeks after vaccination. Further experiments should be carried out to study more aspects of the efficacy of these recombinant viruses before they can be used as a marker vaccine under field circumstances.     

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 na?ve 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.     

A PCV2 vaccine based on genotype 2b is more effective than a 2a-based vaccine to protect against PCV2b or combined PCV2a/2b viremia in pigs with concurrent PCV2, PRRSV and PPV infection

The predominant genotype of porcine circovirus (PCV) in the pig population today is PCV2b yet PCV2a-based commercial vaccines are considered effective in protecting against porcine circovirus associated disease. The objective of this study was to compare the ability of PCV2a- and PCV2b-based vaccines to control PCV2b viremia in a challenge model that mimics the U.S. field situation. Sixty-three pigs were randomly assigned to one of eight groups. Sixteen pigs were vaccinated with an experimental live-attenuated chimeric PCV1-2a vaccine based on genotype 2a and another 16 pigs with a chimeric PCV1-2b vaccine based on genotype 2b. Challenge was done 28 days post vaccination (dpv) using PCV2b (or a combination of PCV2a and PCV2b), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine parvovirus (PPV) to mimic what commonly occurs in the field. The experiment was terminated 21 days post challenge (dpc) or 49 dpv. Pigs vaccinated with the chimeric PCV1-2b vaccine had significantly higher levels of PCV1-2b viremia and shedding of the PCV1-2b vaccine virus in feces and nasal secretions but also a more robust humoral immune response as evidenced by significantly higher ELISA S/P ratios compared to the PCV1-2a vaccination. Regardless of challenge, the PCV1-2b vaccination significantly reduced the prevalence and amount of PCV2 viremia compared to the PCV1-2a vaccination. Interestingly, in the non-vaccinated pigs concurrent PCV2a infection resulted in clinical disease and increased macroscopic lung lesions compared to pigs challenged with PCV2b alone, further supporting the idea that concurrent PCV2a/PCV2b infection is necessary for optimal PCV2 replication.     

Protection in sheep against heterologous challenge with serotype Asia-1 foot-and-mouth disease virus using high potency vaccine

Foot-and-mouth disease virus (FMDV) serotype Asia-1 is prevalent in countries considered high risk for incursion into Australia, and has recently been responsible for a number of outbreaks in India, Bangladesh, Pakistan and Turkey. In vitro vaccine matching has shown a number of contemporary FMDV Asia-1 strains vary antigenically to the Asia-1 Shamir vaccine strain, which could result in poor protection with use of this vaccine. Therefore it was important to test the ability of the Asia-1 Shamir vaccine to protect sheep from challenge with a recent, heterologous strain at different days post-vaccination (dpv), including in an emergency vaccination scenario (challenge 4 or 7 dpv). Sheep (5 per group) were challenged with the Asia-1/PAK/19/2014 isolate by intra-nasopharyngeal instillation 21 (V21), 7 (V7) or 4 (V4) dpv with high-potency (>6 PD₅₀) Asia-1 Shamir vaccine. An additional five sheep were mock-vaccinated with adjuvant only (antigen-free preparation) 4 days prior to challenge (A4), and five unvaccinated (UV) control sheep were also challenged. All V21, V7 and V4 sheep were protected from clinical FMD. Eighty percent of V21 sheep and 40% of V7 sheep had sterile immunity, however all V4 sheep became systemically infected. Vaccination reduced excretion of virus in nasal and oral secretions but had no effect on the development of persistent infection. All A4 sheep and UV control sheep developed clinical FMD. The high-potency Asia-1 Shamir vaccine will protect against disease should an outbreak of contemporary Asia-1 viruses occur. Intranasopharyngeal instillation is an effective challenge method for use in vaccine efficacy studies in sheep.     

Use of ENABL® adjuvant to increase the potency of an adenovirus-vectored foot-and-mouth disease virus serotype A subunit vaccine

A foot-and-mouth disease (FMD) recombinant subunit vaccine formulated with a lipid/polymer adjuvant was evaluated in two vaccine efficacy challenge studies in steers. The vaccine active ingredient is a replication-deficient human adenovirus serotype 5 vector encoding the FMD virus (FMDV) A24/Cruzeiro/BRA/55 capsid (AdtA24). In the first study, AdtA24 formulated in ENABL® adjuvant was compared to a fourfold higher dose of AdtA24 without adjuvant. Steers vaccinated with AdtA24 + ENABL® adjuvant developed a significantly higher virus neutralizing test (VNT) antibody titer and an improved clinical response following FMDV A24/Cruzeiro/BRA/55 intradermal lingual challenge at 14 days post-vaccination (dpv) than steers vaccinated with the active ingredient alone. In the second study, vaccination with AdtA24 formulated in ENABL® at the same dose used in the first study, followed by FMDV A24/Cruzeiro/BRA/55 challenge on 7 or 14 dpv, prevented clinical FMD in all steers and conferred 90% protection against viremia. In addition, post-challenge FMDV titers in nasal samples from vaccinated steers compared to unvaccinated steers were significantly reduced. In both studies, none of the AdtA24 vaccinated steers developed antibodies to the FMDV non-structural proteins prior to challenge with FMDV, indicative of the capacity to differentiate infected from vaccinated animals (DIVA). These results demonstrate that administration of AdtA24 formulated in ENABL® adjuvant lowered the protective dose and prevented clinical FMD following exposure of vaccinated steers to virulent FMDV at 7 or 14 dpv.     

The immunopotentiator CVC1302 enhances immune efficacy and protective ability of foot-and-mouth disease virus vaccine in pigs

The immunological enhancement characteristics of the immunopotentiator CVC1302 were evaluated for foot-and-mouth disease virus (FMDV) inactivated vaccine in pigs. Eight-week-old piglets were vaccinated with the foot-and-mouth disease (FMD) vaccine alone (FMD-vaccine group) or with the addition of CVC1302 (FMD-CVC1302 group), and the serum liquid phase blocking ELISA (LPB-ELISA) antibody titers, IgG1 and IgG2 levels, and the levels of four cytokines secreted by peripheral blood lymphocytes were measured at 28 days post vaccination (dpv). In the FMD-CVC1302 group, the LPB-ELISA antibody titers, IgG1, and IgG2 titers, and IL-2, IL-4, IL-6, and IFN-γ levels at 28 dpv were significantly higher than those in the FMD-vaccine group. The FMD-CVC1302 group had long-lasting antibody titers (>7.8 log₂), lasting for at least 6 months. In addition, piglets were vaccinated with or without addition of CVC1302 to the FMD vaccine at three different doses (1, 1/3, and 1/9 of the standard vaccine dose) and the serum LPB-ELISA antibody and serum neutralizing (SN) antibody titers were detected at 28 dpv. Then all pigs were challenged with virulent FMDV for PD₅₀ value, and the levels of FMDV-specific RNA copies for the two full-dose groups at 3 and 10 days post challenge (dpc) were measured. The LPB-ELISA and SN antibody titers for the three doses in the FMD-CVC1302 groups were significantly higher than those in the FMD-vaccine groups at the same doses (p < 0.05). Post-virus challenge, the FMDV-specific RNA copy number in the FMD-CVC1302 group was lower than that in the FMD-vaccine group at 3 and 10 dpc. The PD₅₀ value was 15.85 for the FMD-CVC1302 group, which was obviously higher than that for the FMD-vaccine group (10.96), and in the 1/9-dose of FMD-vaccine group only 3/5 pigs were protected. These results indicate that CVC1302 can enhance the immune efficacy and protective ability of the FMD vaccine in pigs.     

A foot-and-mouth disease SAT2 vaccine protects swine against experimental challenge with a homologous virus strain,irrespective of mild pathogenicity in this species

FMDV serotype SAT2 is most frequently associated with outbreaks in ruminants. However, the risk of it spreading from cattle to pigs cannot be excluded. To assess the efficacy of an SAT2-type FMD inactivated vaccine against homologous challenge in pigs, a suitable challenge strain adapted to pigs was produced. After two passages in two pigs each, a FMDV stock of SAT2 challenge strain was produced. This material was used to infect two groups of five pigs. The first group being vaccinated 28 days before challenge and the other one left as an unvaccinated control. Clinical signs were recorded, virus shedding was assessed on mouth swabs, and neutralising antibody titres were determined. At least 80% of the vaccinated pigs were protected against clinical disease. Furthermore, no virus shedding was observed in any of the vaccinated pigs. This study shows that experimentally inoculated pigs can become infected with a SAT2 serotype. Furthermore, vaccination offers protection against generalisation and viral excretion, confirming the potential of vaccination as an important tool in the control of FMD in pigs.     

Construction of a triple gene-deleted Chinese Pseudorabies virus variant and its efficacy study as a vaccine candidate on suckling piglets

New-emerging variants of Pseudorabies virus (PRV) compromise the protection provided by current vaccines and cause the death of all ages of vaccinated pigs since 2011. New vaccines based on current circulating PRV strain are needed to control the spread of disease since the variants are antigenically different from classical strains of virus. In this study, a TK/gE/gI triple gene-deleted PRV derived from current circulating field isolate was generated by using bacterial artificial chromosome techniques, and the rescued virus showed similar growth properties in vitro to its parent strain but reduced plaque size. To evaluate it as vaccine candidate, 9 day-old pigs were vaccinated and challenged with a virulent PRV variant. The results showed that vaccination can generate high level of protective gB-specific antibodies after vaccination and provide complete protection to the viral challenge. By contrast, the unvaccinated piglets all died within 6 days after viral challenge. Therefore, the TK/gE/gI triple gene-deleted PRV could be a promising vaccine candidate to control the wide spreading of PR variants in China.     

A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

Emergency vaccination against foot-and-mouth disease: Rate of development of immunity and its implications for the carrier state

Emergency foot-and-mouth disease (FMD) vaccines prepared from antigens held in the International Vaccine Bank at Pirbright were administered to cattle and pigs and the levels of protection were assessed following challenge by contact with infected pigs. Both Al(OH)₃/saponin and oil-based cattle vaccines proved to be extremely effective and protected soon after vaccination (4 days postvaccination), whereas the pigs were seldom protected before 21 and 28 days postvaccination, probably due to lower levels of antibody and overwhelming challenge conditions. Early production of cattle occurred in the absence of significant levels of circulating antibody as measured by enzyme-linked immunosorbent assay, a neutralization assay and a passive protection test. A large number of the cattle vaccinated with the O₁ Lausanne strain of FMD and subsequently challenged with this virus became persistently infected and there appeared to be a correlation with the time interval between vaccination and challenge. When the same cattle were vaccinated approximately 4 months later with a different strain of FMD, C₁ Oberbayern, and challenged with this strain, the number of persistently infected animals was considerably lower. The results are discussed in the context of the use of emergency vaccines to prevent the dissemination of FMD from disease foci.     

Efficacy of an attenuated European subtype 1 porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in pigs upon challenge with the East European subtype 3 PRRSV strain Lena

The efficacy of a commercial attenuated European subtype 1 PRRSV vaccine was evaluated upon challenge with the East European subtype 3 PRRSV strain Lena (83.3% nucleotide identity). Two vaccination experiments were carried out. Four- and seven-week-old pigs were vaccinated with the modified-live vaccine. Upon vaccination, virus specific IPMA antibodies were detected in all vaccinated animals with titers ranging from 10^2.8 to 10^4.6. No virus neutralizing (VN) antibodies were detected after vaccination. Eight (exp. 1) or six (exp. 2) weeks after vaccination, pigs were challenged with 10⁶ (exp. 1) resp. 10⁵ (exp. 2) TCID₅₀ of the European subtype 3 PRRSV Lena. Upon challenge, non-vaccinated animals showed fever during 5.1 (exp. 1) or 7.7 (exp. 2) days. In vaccinated pigs, the duration of fever was reduced by 1.8 (exp. 1) or 3.5 (exp. 2) days. The modified-live virus vaccine reduced the mean duration of nasal shedding and viremia. In non-vaccinated pigs, virus shedding lasted 5.8 days (exp. 1), resp. 8.3 days (exp. 2). This period was reduced to 3.6 (exp. 1), resp. 3.0 (exp. 2) days in vaccinated animals. Viremia was observed during a shorter period in vaccinated (exp. 1: 7.4 days, exp. 2: 4.8 days) than in non-vaccinated groups (exp. 1: 11.8 days, exp. 2: 12.3 days). Starting from 5 days post challenge, virus titers in nasal secretions and sera were significantly lower in vaccinated animals (P < 0.05). Virus-neutralizing antibodies were detected at low titers (≤16) after 7 days post challenge in vaccinated animals and 28 days post challenge in control animals. In conclusion, it can be stated that vaccination of pigs with an attenuated European subtype 1 vaccine provides a partial protection against a subsequent exposure to the highly pathogenic East European subtype 3 PRRSV strain Lena.     

Foot and mouth disease virus transmission among vaccinated pigs after exposure to virus shedding pigs

The aim of this study was to design a transmission experiment that enabled quantification of the effectiveness of vaccination against foot and mouth disease (FMD) virus in groups of pigs. Previous experiments showed that intradermal injection of pigs with FMD virus 14 days after vaccination was not suitable to start an infection chain, as inoculated vaccinated pigs resisted challenge. Therefore, we carried out two experiments in which we used direct contact to a non-vaccinated pig as route of infection. In the first experiment only the vaccine effect on susceptibility was quantified by exposing pigs, either vaccinated 14 days before or not vaccinated, each to a non-vaccinated seeder pig inoculated with FMD virus O/NET/2001. Since no significant differences were observed between contact infections in vaccinated or non-vaccinated pigs, we performed a second experiment in which both susceptibility and infectivity were subject to vaccination. We quantified virus transmission in homogenous groups of vaccinated or non-vaccinated pigs in which the infection chain was started by exposure to a third group of non-vaccinated infected pigs. Transmission occurred to all contact-exposed pigs in the non-vaccinated groups and to 9 out of 10 contact-exposed pigs in the vaccinated groups. The rate of transmission (beta) was significantly reduced in the vaccine group. Yet, the estimated reproduction ratio in both groups was still above 1. In conclusion, by adjusting our transmission study design and challenge method, we were able to quantify transmission of FMDV among vaccinated pigs. According to this study a single vaccination was not sufficient to stop pig to pig virus transmission. With these results major outbreaks may still be expected, even in groups of vaccinated pigs.     

Evaluation of the efficacy and safety of the Rift Valley Fever Clone 13 vaccine in sheep

The efficacy and safety of the naturally attenuated Rift Valley Fever (RVF) Clone 13 vaccine were evaluated in ovines in three different experiments involving 38 ewes at different stages of pregnancy, their offsprings and four rams. In Experiment 1, 4 rams and a total of 13 pregnant ewes were vaccinated and monitored during vaccination and after a challenge with a virulent RVF virus. The ewes were vaccinated at either 50 or 100 days of pregnancy and some were challenged after lambing. In Experiment 2, nine oestrus-synchronized ewes were vaccinated at 50 days of pregnancy and challenged at 100 days of pregnancy together with 5 unvaccinated ewes at the same stage of pregnancy. In Experiment 3, 16 oestrus-synchronized ewes were vaccinated with 3 different doses of the RVF Clone 13 vaccine and challenged together with unvaccinated pregnant ewes at either 30 or 50 days of pregnancy. The results from the three experiments indicated that the vaccine did not induce clinical manifestation of RVF such as abortion in pregnant ewes, teratogeny in their offsprings, or pyrexia in all vaccinated animals. Vaccination with RVF Clone 13 vaccine also prevented clinical RVF following virulent challenge at different stages of pregnancy while unvaccinated control ewes showed pyrexia, aborted or died of RVF. A vaccine dose–response effect was also observed.     

Efficacy of a high potency O1 Manisa foot-and-mouth disease vaccine in cattle against heterologous challenge with a field virus from the O/ME-SA/Ind-2001 lineage collected in North Africa

Outbreaks of foot-and-mouth disease (FMD) in North Africa (2013) and the Gulf States (2013) of the Middle East have been caused by a FMD viral lineage (O/ME-SA/Ind-2001) that was before 2013 restricted to the Indian Sub-continent. This study was undertaken to assess the in vivo efficacy of a FMD virus emergency vaccine type O₁ Manisa against heterologous challenge with a representative field virus (O/ALG/3/2014) from this emerging lineage. This widely available vaccine was selected since in vitro vaccine-matching results gave inconclusive results as to whether or not it would be protective. Three groups of five cattle were vaccinated with O₁ Manisa (homologous potency ≥6PD₅₀/dose) using study guidelines outlined in the European Pharmacopeia, and challenged at 21 days post-vaccination by tongue inoculation. All animals that were vaccinated with the lowest dose (1/16) of vaccine developed generalised FMD, defined as vesicular lesions at the feet. One animal vaccinated with a 1/4 dose of the vaccine also developed generalised disease, as did two animals vaccinated with the full dose of vaccine. These results indicate that the heterologous potency of this high potency O₁ Manisa vaccine was approximately 3.5 PD₅₀/dose. These data support the use of the O₁ Manisa vaccine for FMD control in areas where FMDV is endemic e.g. North Africa, and motivate further studies to evaluate other vaccine candidates (or multivalent combinations) that might be potentially used for emergency purposes in FMD-free settings.