Modified-live Virus Vaccine Research Articles

Effect of immunologic solutions on sows and gilts on time to stability, and production losses in breeding herds infected with 1-7-4 PRRSv

Porcine reproductive and respiratory syndrome virus (PRRSv) is an economically significant swine pathogen causing production losses in the global swine industry. Clinical impact depends on many factors including the virus itself. One method to sub-type PRRSv is using restriction fragment length polymorphism (RFLP). The RFLP pattern 1-7-4 emerged within the United States swine industry in 2014 and has become prevalent since then. This was a field study that prospectively followed 1-7-4-infected breeding herds (n=107) and compared time to stability (TTS), time to baseline production (TTBP) and total loss per 1000 sows between herds using modified-live virus vaccine (MLV) on sows and gilts (MLV-MLV), MLV on sows and MLV in addition to field virus exposure on gilts (MLV–MLV/FVE) or not deliberately exposing sows or gilts to PRRSv (Natural-Natural). Analyses were done in SAS 9.4 and results were adjusted by selected co-variates (duration of herd closure, number of previous PRRSv outbreaks of last 3 years, weaning frequency/week, gilt development unit location, herd size and production system). Survival analysis was conducted on TTS and TTBP and regression analysis on total loss. Herds in the Natural–Natural group achieved TTS and TTBP before other herds. Herds in the MLV-MLV/FVE had the longest TTS and TTBP. The total loss was numerically least in MLV–MLV herds (1194 pigs/1000 sows) compared to MLV/MLV-FVE (1810/1000 sows) and Natural–Natural (2671/1000 sows). This study provided additional information to assist veterinarians deciding between methods of exposure to manage PRRSv infection from breeding herds.

Efficacy evaluation of three modified-live virus vaccines against a strain of porcine reproductive and respiratory syndrome virus NADC30-like

Porcine reproductive and respiratory syndrome reproductive virus is a devastating pathogen causing tremendous economic losses to swine production worldwide. Emergence of novel and variant PRRSV strains always leads to variable protection efficacy of modified-live virus (MLV) vaccines. Prevalence of PRRSV NADC30-like recently emerging in China has brought about clinical outbreaks of the disease. In the present study, the pathogenicity of a NADC30-like strain CHsx1401 for piglets was analyzed, and the potential cross-protective efficacy of three MLV vaccines including two commercial MLV vaccines and an attenuated low pathogenic PRRSV against this virus was further evaluated in piglets. The NADC30-like CHsx1401 was shown to cause fever, respiratory clinical signs, and lung gross and microscopic lesions of the inoculated piglets, suggesting that this virus is moderate virulent for piglets. Vaccination of piglets with the MLV vaccines could not reduce the clinical signs and lung lesions, and was partially efficacious in the reduction of viral loads in sera upon NADC30-like CHsx1401 challenge, indicating that these three MLV vaccines provide extremely limited cross-protection efficacy against the NADC30-like virus infection. Additionally, Ingelvac PRRS MLV appeared to exert some beneficial efficiency in shortening the period of clinical fever and in improving the growth performance of the challenged pigs. Our findings give valuable guidance for the choice and use of PRRSV MLV vaccines to control NADC30-like virus infection in the field.

Virus detection by PCR following vaccination of naive calves with intranasal or injectable multivalent modified-live viral vaccines.

We evaluated duration of PCR-positive results following administration of modified-live viral (MLV) vaccines to beef calves. Twenty beef calves were randomly assigned to either group 1 and vaccinated intranasally with a MLV vaccine containing bovine alphaherpesvirus 1 (BoHV-1), bovine respiratory syncytial virus (BRSV), and bovine parainfluenza virus 3 (BPIV-3), or to group 2 and vaccinated subcutaneously with a MLV vaccine containing bovine viral diarrhea virus 1 and 2 (BVDV-1, -2), BoHV-1, BRSV, and BPIV-3. Deep nasopharyngeal swabs (NPS) and transtracheal washes (TTW) were collected from all calves, and whole blood was collected from group 2 calves and tested by PCR. In group 1, the proportions of calves that tested PCR-positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 0%, 100%, 100%, and 10%, respectively. In group 1 calves, 100% of calves became PCR-positive for BoHV-1 by day 3 post-vaccination and 100% of calves became PCR-positive for BRSV by day 7 post-vaccination. In group 2, the proportions of calves that tested positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 50%, 40%, 10%, and 0%, respectively. All threshold cycle (Ct) values were >30 in group 2 calves, irrespective of virus; however, Ct values <25 were observed in group 1 calves from PCR-positive results for BoHV-1 and BRSV. All calves were PCR-negative for all viruses after day 28. Following intranasal MLV viral vaccination, PCR results and Ct values for BRSV and BoHV-1 suggest that attempts to differentiate vaccine virus from natural infection is unreliable.

Evaluation of porcine reproductive and respiratory syndrome stabilization protocols in 23 French Farrow-to-finish farms located in a high-density swine area

BackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) is responsible for reproductive disorders in sows and respiratory problems in pigs, and has a major economic impact. Controlling PRRSV is therefore a priority for the swine industry. Stabilization of a herd, defined as the production of PRRSV-negative pigs at weaning from seropositive sows, is a common method of control, and different protocols have been described in the literature to achieve this stabilization.Context and purposeThe objective of this study was to evaluate wether the combination of mass vaccination of sows and their piglets with a Genotype I modified live virus (MLV) vaccine, with temporal closure to the introduction of replacement animals and unidirectional pig and human flow can result in the production of PRRSV-negative pigs at weaning. The study took place in French farrow-to-finish farms located in a high-density swine area where the disease concerns over 60% of farms and only closely related strains of genotype I have been reported. Twenty-three 100-to-700 sow farrow-to-finish farms were selected prospectively between 2005 and 2014, regardless of their biosecurity level. Those farms adopted a stabilization protocol characterized by the following standardized measures: vaccination of sows, gilts, and piglets with the Genotype I MLV vaccine PORCILIS®PRRS, temporary herd closure, and strict internal biosecurity measures. Monitoring of herd status was then performed using a combination of 3 diagnostic tools: Real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Open reading frame (ORF) 5 and ORF7 sequencing. The status of finishing units (either active or inactive, meaning PRRSV-positive or PRRSV-negative, respectively) was not considered in this study.Results and conclusionsAt the end of the monitoring period, considering the results of all the analyses, clinical signs, and epidemiology, 19 farms were considered stable and 1 remained unstable. In 3 farms it was commonly agreed to extend the number of vaccinated batches of piglets, which enabled them to be considered stable at the end of a second round of monitoring. The combination of vaccination of sows and their piglets with a Genotype I MLV vaccine, together with the closure of the farm and a unidirectional pig and human flow, seems to be effective for farrow–to-finish farms even in high-density swine area, even with French PRRSV strains closely related to one another. This research is the first European study examining such a large number of farms, and increased confidence in the results stems from the added value of using the ORF7 and ORF5 sequencing tool.

Preparation for emergence of an Eastern European porcine reproductive and respiratory syndrome virus (PRRSV) strain in Western Europe: Immunization with modified live virus vaccines or a field strain confers partial protection

The porcine reproductive and respiratory syndrome virus (PRRSV) causes huge economic losses for the swine industry worldwide. In the past several years, highly pathogenic strains that lead to even greater losses have emerged. For the Western European swine industry, one threat is the possible introduction of Eastern European PRRSV strains (example Lena genotype 1.3) which were shown to be more virulent than common Western resident strains under experimental conditions. To prepare for the possible emergence of this strain in Western Europe, we immunized piglets with a Western European PRRSV field strain (Finistere: Fini, genotype 1.1), a new genotype 1 commercial modified live virus (MLV) vaccine (MLV1) or a genotype 2 commercial MLV vaccine (MLV2) to evaluate and compare the level of protection that these strains conferred upon challenge with the Lena strain 4 weeks later. Results show that immunization with Fini, MLV1 or MLV2 strains shortened the Lena-induced hyperthermia. In the Fini group, a positive effect was also demonstrated in growth performance. The level of Lena viremia was reduced for all immunized groups (significantly so for Fini and MLV2). This reduction in Lena viremia was correlated with the level of Lena-specific IFNγ-secreting cells. In conclusion, we showed that a commercial MLV vaccine of genotype 1 or 2, as well as a field strain of genotype 1.1 may provide partial clinical and virological protection upon challenge with the Lena strain. The cross-protection induced by these immunizing strains was not related with the level of genetic similarity to the Lena strain. The slightly higher level of protection established with the field strain is attributed to a better cell-mediated immune response.

Genomic and antigenic characterization of bovine parainfluenza-3 viruses in the United States including modified live virus vaccine (MLV) strains and field strains from cattle

This study investigated the genetic and antigenic characterization of parainfluenza-3 virus (PI3V) of cattle. Using molecular tests including real time PCR and viral genome sequencing, PI3V strains could be separated into PI3V types, including PI3V A, PI3V B, and PI3V C. Isolates from cattle with bovine respiratory disease clinical signs and commercial vaccines in the U.S. with MLV PI3V were typed using these molecular tests. All the MLV vaccine strains tested were PI3V A. In most cases PI3V field strains from calves receiving MLV vaccines were types heterologous to the vaccine type A. Also antigenic differences were noted as PI3V C strains had lower antibody levels than PI3V A in serums from cattle receiving MLV PI3V A vaccines. This study further demonstrates there is genetic variability of U.S. PI3V strains and also antigenic variability. In addition, isolates from cattle with BRD signs and receiving MLV vaccines may have heterologous types to the vaccines, and molecular tests should be performed to differentiate field from vaccine strains. Potentially the efficacy of current PI3V A vaccines should be evaluated with other types such a PI3V B and PI3V C.

Vaccination of cattle against bovine viral diarrhea virus

Bovine viral diarrhea virus (BVDV) is responsible for significant losses to the cattle industry. Currently, modified-live viral (MLV) and inactivated viral vaccines are available against BVDV, often in combination with other viral and bacterial antigens. Inactivated and MLV vaccines provide cattle producers and veterinarians safe and efficacious options for herd immunization to limit disease associated with BVDV infection. Vaccination of young cattle against BVDV is motivated by prevention of clinical disease and limiting viral spread to susceptible animals. For reproductive-age cattle, vaccination to prevent viremia and birth of persistently infected offspring is considered more important, while also more difficult to achieve than prevention of clinical disease. Recent advances have been made in the understanding of BVDV vaccine efficacy. In terms of preventing clinical disease, current BVDV vaccines have been demonstrated to have a rapid onset of immunity and MLV vaccines can be effectively utilized in calves possessing maternal immunity. For reproductive protection, more recent studies using multivalent MLV vaccines have demonstrated consistent fetal protection rates in the range of 85–100% in experimental studies. Proper timing and administration of BVDV vaccines can be utilized to maximize vaccine efficacy to provide an important contribution to reducing risks associated with BVDV infection. With improvements in vaccine formulations and increased understanding of the protective immune response following vaccination, control of BVDV through vaccination can be enhanced.

Effect of modified-live bovine viral diarrhea virus type 2 vaccine on performance, health, temperature, and behavior response in high-risk beef heifer calves

The objective of this study was to determine performance, health, vaginal temperature, and behavior differences in calves vaccinated upon feedlot arrival with a multivalent modified-live virus (MLV) vaccine which included bovine viral diarrhea virus (BVDV) type 2 antigen and calves vaccinated with a vaccine which did not include BVOV type 2. Eightythree beef heifer calves were randomly assigned to receive a multivalent MLV vaccine containing either bovine herpesvirus-1, BVDV type 1, bovine respiratory syncytial virus, and parainfluenza type-3 virus (n = 42; 4-WAY), or a MLVvaccine of similar formulation which also contained a BVDV type 2 antigen (n = 41; 5-WAY). Performance outcomes were evaluated at 30 and 60 days. Vaginal temperatures were evaluated hourly and daily. Cattle behavior activity was monitored with a real-time location system. Calves in the 5-WAY group had greater average daily gain (P = 0.026) at 60 days, excluding dead animals, compared to 4-WAY group. Treatment group was not associated with vaginal temperature. Calves in 5-WAY spent a greater (P ~ 0.01) amount of time at the feed bunk on days 0, 2, 3, and 4 compared to 4-WAY. Results of this study indicate no adverse effects from administering an additional strain of BVOV type 2 to high-risk heifers. Behavioral responses indicate a potential advantage to administer 5-WAY vaccine compared to 4-WAY vaccine.

Evaluation of reproductive protection against bovine viral diarrhea virus and bovine herpesvirus-1 afforded by annual revaccination with modified-live viral or combination modified-live/killed viral vaccines after primary vaccination with modified-live viral vaccine

The objective of this study was to compare reproductive protection in cattle against bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BoHV-1) provided by annual revaccination with multivalent modified-live viral (MLV) vaccine or multivalent combination viral (CV) vaccine containing temperature-sensitive modified-live BoHV-1 and killed BVDV when MLV vaccines were given pre-breeding to nulliparous heifers. Seventy-five beef heifers were allocated into treatment groups A (n=30; two MLV doses pre-breeding, annual revaccination with MLV vaccine), B (n=30; two MLV doses pre-breeding, annual revaccination with CV vaccine) and C (n=15; saline in lieu of vaccine). Heifers were administered treatments on days 0 (weaning), 183 (pre-breeding), 366 (first gestation), and 738 (second gestation). After first calving, primiparous cows were bred, with pregnancy assessment on day 715. At that time, 24 group A heifers (23 pregnancies), 23 group B heifers (22 pregnancies), and 15 group C heifers (15 pregnancies) were commingled with six persistently infected (PI) cattle for 16days. Ninety-nine days after PI removal, cows were intravenously inoculated with BoHV-1. All fetuses and live offspring were assessed for BVDV and BoHV-1. Abortions occurred in 3/23 group A cows, 1/22 group B cows, and 11/15 group C cows. Fetal infection with BVDV or BoHV-1 occurred in 4/23 group A offspring, 0/22 group B offspring, and 15/15 group C offspring. This research demonstrates efficacy of administering two pre-breeding doses of MLV vaccine with annual revaccination using CV vaccine to prevent fetal loss due to exposure to BVDV and BoHV-1.

Priming Cross-Protective Bovine Viral Diarrhea Virus-Specific Immunity Using Live-Vectored Mosaic Antigens.

Bovine viral diarrhea virus (BVDV) plays a key role in bovine respiratory disease complex, which can lead to pneumonia, diarrhea and death of calves. Current vaccines are not very effective due, in part, to immunosuppressive traits and failure to induce broad protection. There are diverse BVDV strains and thus, current vaccines contain representative genotype 1 and 2 viruses (BVDV-1 & 2) to broaden coverage. BVDV modified live virus (MLV) vaccines are superior to killed virus vaccines, but they are susceptible to neutralization and complement-mediated destruction triggered by passively acquired antibodies, thus limiting their efficacy. We generated three novel mosaic polypeptide chimeras, designated NproE2123; NS231; and NS232, which incorporate protective determinants that are highly conserved among BVDV-1a, 1b, and BVDV-2 genotypes. In addition, strain-specific protective antigens from disparate BVDV strains were included to broaden coverage. We confirmed that adenovirus constructs expressing these antigens were strongly recognized by monoclonal antibodies, polyclonal sera, and IFN-γ-secreting T cells generated against diverse BVDV strains. In a proof-of-concept efficacy study, the multi-antigen proto-type vaccine induced higher, but not significantly different, IFN-γ spot forming cells and T-cell proliferation compared to a commercial MLV vaccine. In regards to the humoral response, the prototype vaccine induced higher BVDV-1 specific neutralizing antibody titers, whereas the MLV vaccine induced higher BVDV-2 specific neutralizing antibody titers. Following BVDV type 2a (1373) challenge, calves immunized with the proto-type or the MLV vaccine had lower clinical scores compared to naïve controls. These results support the hypothesis that a broadly protective subunit vaccine can be generated using mosaic polypeptides that incorporate rationally selected and validated protective determinants from diverse BVDV strains. Furthermore, regarding biosafety of using a live vector in cattle, we showed that recombinant human adenovirus-5 was cleared within one week following intradermal inoculation.

Prevention of abortion in cattle following vaccination against bovine herpesvirus 1: A meta-analysis

Bovine herpesvirus 1 is ubiquitous in cattle populations and is the cause of several clinical syndromes including respiratory disease, genital disease, and late-term abortions. Control of the virus in many parts of the world is achieved primarily through vaccination with either inactivated or modified-live viral vaccines. The purpose of this meta-analysis was to determine the cumulative efficacy of BoHV-1 vaccination to prevent abortion in pregnant cattle. Germane articles for inclusion in the analysis were identified through four online scientific databases and the examination of three review and ten primary study article reference lists. A total of 15 studies in 10 manuscripts involving over 7500 animals were included in the meta-analysis. Risk ratio effect sizes were used in random effects, weighted meta-analyses to assess the impact of vaccination. Subgroup analyses were performed based on type of vaccine, MLV or inactivated, and the type of disease challenge, experimentally induced compared to field studies. A 60% decrease in abortion risk in vaccinated cattle was demonstrated. The greatest decrease in abortion risk was seen in studies with intentional viral challenge although vaccination also decreased abortion risk in field studies. Both inactivated and modified-live viral vaccines decreased abortion risk. This meta-analysis provides quantitative support for the benefit of bovine herpesvirus 1 vaccination in the prevention of abortion.

Influence of vaccination with an inactivated or modified live viral reproductive vaccine on reproductive parameters in beef cows

Previous research has described the detrimental effects of modified-live virus (MLV) vaccines on reproductive parameters in na'ive heifers. Less is known about the patential effects of MLV vaccines on reproductive parameters in well-vaccinated beef herds. This work describes a 2-year study involving 9 herds of well-vaccinated cows and heifers (n=1436) to evaluate whether a pre-breeding MLV or inactivated reproductive vaccine administered per label instructions had negative impacts on conception rates or calving distribution compared to a non-vaccinated control (saline) group.

Dexamethasone treatment differentially alters viral shedding and the antibody and acute phase protein response after multivalent respiratory vaccination in beef steers.

Our objective was to examine immunosuppression induced by dexamethasone (DEX) administration in cattle on immunological responses to a multivalent respiratory vaccine containing replicating and nonreplicating agents. Steers ( = 32; 209 ± 8 kg) seronegative to infectious bovine rhinotracheitis virus (IBRV), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), and parainfluenza-3 virus (PI3V) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) acute immunosuppression (ACU; 0.5 mg/kg BW DEX intravenously at 1000 h only on d 0), 2) chronic immunosuppression (CHR; 0.5 mg/kg BW DEX intravenously at 1000 h on d -3 to 0), or 3) a control (CON; no DEX). On d -4, steers were fitted with intravenous catheters in the jugular vein and placed into individual stanchions. At 1200 h on d 0, steers were administered a respiratory vaccine containing modified-live virus (MLV) isolates of IBRV, BVDV, BRSV, and PI3V and a (MH) toxoid. On d 4, cattle were transported (177 km) and housed in an isolated outdoor pen. Serum was harvested on d 0, 7, 14, 21, 28, 35, 42, and 56 to determine IBRV-, BVDV-, BRSV-, and PI3V-specific antibody titers and MH whole cell and leukotoxin antibody concentrations. Sera from d -2, 0, 1, 3, 7, and 14 were used to quantify haptoglobin (Hp) concentration and ceruloplasmin (Cp) activity. Nasal swab specimens were collected on d 0, 3, and 14 to determine the presence of IBRV, BVDV, BRSV, and PI3V via PCR analysis. There was a treatment × day interaction ( < 0.01) such that CHR steers had a greater ( ≤ 0.07) BVDV antibody titer on d 14, 21, and 28. Moreover, IBRV-specific antibodies increased beginning on d 14 for CHR and on d 28 for ACU and remained greater through d 56 compared with CON ( ≤ 0.03). Conversely, serum MH whole cell antibody concentration was least ( ≤ 0.06) for CHR from d 7 to 28 and greatest for CON ( ≤ 0.04) on d 56. Treatment altered Hp such that CON exhibited a greater ( < 0.01) Hp concentration than CHR but was not different from ACU ( = 0.16). On d 3, Cp was greatest for CON, intermediate for ACU, and least for CHR (treatment × day; ≤ 0.01). The prevalence of IBRV and BVDV in nasal swabs on d 14 was 67 and 56%, respectively, for CHR; 10 and 10%, respectively, for CON; and 9 and 0%, respectively, for ACU ( ≤ 0.006). Results suggest that CHR allowed increased replication of MLV vaccine agents. Conversely, DEX-induced immunosuppression blunted the acute phase protein and antibody response against the nonreplicating MH toxoid.

Effects of injectable trace minerals on humoral and cell-mediated immune responses to Bovine viral diarrhea virus, Bovine herpes virus 1 and Bovine respiratory syncytial virus following administration of a modified-live virus vaccine in dairy calves

Our objective was to evaluate the effect of an injectable trace mineral (ITM) supplement containing zinc, manganese, selenium, and copper on the humoral and cell mediated immune (CMI) responses to vaccine antigens in dairy calves receiving a modified-live viral (MLV) vaccine containing BVDV, BHV1, PI3V and BRSV. A total of 30 dairy calves (3.5 months of age) were administered a priming dose of the MLV vaccine containing BHV1, BVDV1 & 2, BRSV, PI3V, and an attenuated-live Mannheimia-Pasteurella bacterin subcutaneously (SQ). Calves were randomly assigned to 1 of 2 groups: (1) administration of ITM SQ (ITM, n=15) or (2) injection of sterile saline SQ (Control; n=15). Three weeks later, calves received a booster of the same vaccine combination SQ, and a second administration of ITM, or sterile saline, according to the treatment group. Blood samples were collected on days 0, 7, 14, 21, 28, 42, 56, and 90 post-vaccination for determination of antibody titer, viral recall antigen-induced IFN-γ production, and viral antigen-induced proliferation by peripheral blood mononuclear cells (PBMC). Administration of ITM concurrently with MLV vaccination resulted in higher antibody titers to BVDV1 on day 28 after priming vaccination compared to the control group (P=0.03). Calves treated with ITM showed an earlier enhancement in PBMC proliferation to BVDV1 following vaccination compared to the control group. Proliferation of PBMC after BVDV stimulation tended to be higher on day 14 after priming vaccination in calves treated with ITM than in the control group (P=0.08). Calves that received ITM showed higher PBMC proliferation to BRSV stimulation on day 7 after priming vaccination compared to the control group (P=0.01). Moreover, calves in the ITM group also had an enhanced production IFN-γ by PBMC after stimulation with BRSV on day 21 after priming vaccination compared to day 0 (P<0.01). In conclusion, administration of ITM concurrently with MLV vaccination in dairy calves resulted in increased antibody titer to BVDV1, and greater PBMC proliferation to BVDV1 and BRSV recall stimulation compared to the control group, suggesting that ITM might represent a promising tool to enhance the humoral and CMI responses to MLV vaccines in cattle.

Efficacy of Fostera® PRRS modified live virus (MLV) vaccination strategy against a Thai highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection.

Recently, the Chinese highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) (HP-PRRSV) belonging to lineage 8 causes severe symptom with high morbidity and high mortality rates to the Asian pig industry. A recent study showed that pigs immunized with Fostera® PRRS modified live virus (MLV) of lineage 8 could provide a degree of protection against a Vietnamese HP-PRRSV infection. It should be noted that PRRSV commonly found after weaning causes porcine respiratory disease complex (PRDC). Vaccination strategy should be evaluated in each farm scenario. Eighty-one PRRSV-free piglets obtained from a PRRS-free herd were divided into two experiments with the major difference of infection timing after vaccination, 42days in experiment 1 (n = 42) and 28days in experiment 2 (n = 39). Each experiment had similar protocol containing three groups including a negative control, unvaccinated challenged, and vaccinated challenged groups. Pigs in vaccination groups were immunized with Fostera® PRRS MLV vaccine at 3weeks of age. Then, unvaccinated challenged and vaccinated challenged groups were intranasally inoculated with a Thai HP-PRRSV (10PL01). Vaccinated challenged pigs showed significantly lower levels of mean rectal temperatures, clinical severity, lung lesion scores, and viral titers in serum and lung tissue compared to the unvaccinated challenged pigs (p < 0.05). Vaccinated challenged pigs had higher survival rate than those of unvaccinated challenged pigs in both experiments. It should be noted that pigs challenged 42days after vaccination showed a better performance than pigs challenged 28days after vaccination. In conclusion, Fostera® PRRS MLV vaccine was able to improve the survival rate against the Thai HP-PRRSV infection in both 42- and 28-day vaccination-to-infection protocols.

Immune responses to modified live virus vaccines developed from classical or highly pathogenic PRRSV following challenge with a highly pathogenic PRRSV strain

Modified live virus vaccines (MLVs) are used on swine farms to control porcine reproductive and respiratory syndrome virus (PRRSV). MLVs from classical PRRSV (C-PRRSV) provide some protection against emergent highly pathogenic PRRSV (HP-PRRSV). This study characterized the protective efficacy and immune response to MLVs from C-PRRSV (CH-1R) or HP-PRRSV (HuN4-F112) in a challenge using HP-PRRSV (HuN4). The outcomes were clinical signs of disease, pathological changes in the thymus and lungs, viremia, and humoral and cellular immune responses. CH-1R provided some protection against challenge with HuN4, while HuN4-F112 was protective in the HuN4 challenge. Compared to unvaccinated piglets, the vaccinated piglets had milder symptoms and fewer pathological changes in the lung and thymus. Piglets vaccinated with HuN4-F112 had higher antibody titers and lower viral loads than piglets vaccinated with CH-1R post challenge. The differences in outcome between the MLVs suggested that underlying differences in the immune responses might warrant further study.

Innate and specific immune responses to intranasal modified-live EHV-1 virus vaccination in previously immunised equids - a pilot

Previous studies investigating the potential involvement of viruses in airway inflammation were based either on serological tests or on PCR from nasal swabs only. The objectives of this study were to determine the incidence of welland less-characterised viruses in the equine airways, and their association with clinical signs. In a 2-year prospective longitudinal study, nasal swabs (NS) and tracheal washes (TW) were collected monthly on 52 Standardbred racehorses at training (581 samples). Equine aand g-herpesviruses, equine rhinitis virus-A and -B, equine adenovirus-A, and equine influenza virus were investigated by qPCR. Any positive sample was subcategorised as non-quantifiable (>LOD and LOQ). Clinical signs (nasal discharge, coughing), and tracheal mucus score were simultaneously recorded. In TW, respective monthly incidences were 27.9% (EHV-5), 24.8% (EHV-2), 7.1% (ERBV), 3.8% (EHV-4), 1.9% (EAdV1) and 0.2% (EHV-1, ERAV). EIV has not been detected in any sample. Molecular detection of EHV-2 and ERBV in TW were significantly associated with coughing (OR 3.1; 95% CI 1.4-7.1; P1⁄40.01 and OR 5.3; 95% CI 2.1-14.0; P<0.001, respectively). Positive samples for EHV-2 in TW were significantly associated with tracheal mucus score 2 (OR 2.1; 95% CI 1.2-3.8; P1⁄40.02). When based on quantifiable detection, ERBV only was significantly associated with coughing (OR 15.0; 95% CI 3.7-60.0; P<0.001). Positive samples for any virus in NS were not associated with clinical signs. Based on our data, detecting ERBV in TW is a major risk-factor of coughing. This virus should be considered when investigating horses with inflammatory airway disease.

Efficacy of commercial genotype 1 porcine reproductive and respiratory syndrome virus (PRRSV) vaccine against field isolate of genotype 2 PRRSV

Although several recent studies have found that type 1 porcine reproductive and respiratory syndrome virus (PRRSV) modified live virus (MLV) vaccine showed appreciable levels of cross-protection against type 2 PRRSV infection, the possibility of cross-protection between two genotype of PRRSV is still controversial. To determine potential protective efficacy against hetero-genotype field strain of PRRSV and to improve understandings of the mechanisms underlying performance improvement after infection in vaccinated animals, piglets were vaccinated with type 1 PRRSV MLV vaccine and challenged with type 2 field strain of PRRSV. As a result, vaccinated animals gained on average 8.45kg in comparison to 4.77kg measured in non-vaccinated animals during a 3-week period after viral challenge, which shows using a certain PRRSV vaccine could be clinically effective against heterologous genotypic virus challenge. In vaccinated animals, viremia was reduced and cleared rapidly, whilst viral load was much higher and reduced more slowly, indicating rebound viremia in non-vaccinated animals. The titers of neutralizing antibody against the type 2 PRRSV did not exceed the protective level in any animal from both vaccinated and control groups. Instead, antibody avidity of vaccinated animals was much higher than in the control group clearly. Furthermore, a strong negative correlation between antibody avidity and viremia was noted in 80% of vaccinated animals. Through those results from tests evaluating degree of antibody maturation and its relevance with clearing viremia, it could be suggested that non-neutralizing antibodies induced by vaccination prior to challenge might play a key role in protection against PRRSV infection, especially in early time course.

The Attenuation Phenotype of a Ribavirin-Resistant Porcine Reproductive and Respiratory Syndrome Virus Is Maintained during Sequential Passages in Pigs.

In a previous study, ribavirin-resistant porcine reproductive and respiratory syndrome virus (PRRSV) mutants (RVRp13 and RVRp22) were selected, and their resistance against random mutation was shown in cultured cells. In the present study, these ribavirin-resistant mutants were evaluated in terms of their genetic and phenotypic stability during three pig-to-pig passages in comparison with modified live virus (MLV) (Ingelvac PRRS MLV). Pigs challenged with RVRp22 had significantly lower (P< 0.05) viral loads in sera and tissues than pigs challenged with MLV or RVRp13 at the first passage, and the attenuated replication of RVRp22 was maintained until the third passage. Viral loads in sera and tissues dramatically increased in pigs challenged with MLV or RVRp13 during the second passage. Consistently, all five sequences associated with the attenuation of virulent PRRSV in RVRp13 and MLV quickly reverted to wild-type sequences during the passages, but two attenuation sequences were maintained in RVRp22 even after the third passage. In addition, RVRp22 showed a significantly lower (P< 0.001) mutation frequency in nsp2, which is one of the most variable regions in the PRRSV genome, than MLV. Nine unique mutations were found in open reading frames (ORFs) 1a, 2, and 6 in the RVRp22 genome based on full-length sequence comparisons with RVRp13, VR2332 (the parental virus of RVRp13 and RVRp22), and MLV. Based on these results, it was concluded that RVRp22 showed attenuated replication in pigs; further, because of the high genetic stability of RVRp22, its attenuated phenotype was stable even after three sequential passages in pigs. PRRSV is a rapidly evolving RNA virus. MLV vaccines are widely used to control PRRS; however, there have been serious concerns regarding the use of MLV as a vaccine virus due to the rapid reversion to virulence during replication in pigs. As previously reported, ribavirin is an effective antiviral drug against many RNA viruses. Ribavirin-resistant mutants reemerged by escaping lethal mutagenesis when the treatment concentration was sublethal, and those mutants were genetically more stable than parental viruses. In a previous study, two ribavirin-resistant PRRSV mutants (RVRp13 and RVRp22) were selected, and their higher genetic stability was shown in vitro Consequently, in the present study, both of the ribavirin-resistant mutants were evaluated in terms of their genetic and phenotypic stability in vivo RVRp22 was found to exhibit higher genetic and phenotypic stability than MLV, and nine unique mutations were identified in the RVRp22 genome based on a full-length sequence comparison with the RVRp13, VR2332, and MLV genomes.

Efficacy of four commercially available multivalent modified-live virus vaccines against clinical disease, viremia, and viral shedding in early-weaned beef calves exposed simultaneously to cattle persistently infected with bovine viral diarrhea virus and cattle acutely infected with bovine herpesvirus 1.

To evaluate the efficacy of 4 commercially available multivalent modified-live virus vaccines against clinical disease, viremia, and viral shedding caused by bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BHV1) in early-weaned beef calves. 54 early-weaned beef steers (median age, 95 days). Calves were randomly assigned to 1 of 5 groups and administered PBSS (group A [control]; n = 11) or 1 of 4 commercially available modified-live virus vaccines that contained antigens against BHV1, BVDV types 1 (BVDV1) and 2 (BVDV2), parainfluenza type 3 virus, and bovine respiratory syncytial virus (groups B [11], C [10], D [11], and E [11]). Forty-five days after vaccination, calves were exposed simultaneously to 6 cattle persistently infected with BVDV and 8 calves acutely infected with BHV1 for 28 days (challenge exposure). For each calf, serum antibody titers against BVDV and BHV1 were determined before vaccination and before and after challenge exposure. Virus isolation was performed on nasal secretions, serum, and WBCs at predetermined times during the 28-day challenge exposure. None of the calves developed severe clinical disease or died. Mean serum anti-BHV1 antibody titers did not differ significantly among the treatment groups at any time and gradually declined during the study. Mean serum anti-BVDV antibody titers appeared to be negatively associated with the incidence of viremia and BVDV shedding. The unvaccinated group (A) had the lowest mean serum anti-BVDV antibody titers. The mean serum anti-BVDV antibody titers for group D were generally lower than those for groups B, C, and E. Results indicated differences in vaccine efficacy for the prevention of BVDV viremia and shedding in early-weaned beef calves.