Modified-live Vaccine Research Articles

Antibody Response to Canine Parvovirus Vaccination in Dogs with Hyperadrenocorticism Treated with Trilostane.

It is unknown how dogs with hyperadrenocorticism (HAC) respond to vaccination. This study measured antibodies against canine parvovirus (CPV) in dogs with HAC treated with trilostane before and after CPV vaccination, and compared the immune response to that from healthy dogs. Eleven dogs with HAC, and healthy age-matched control dogs (n = 31) received a modified-live CPV vaccine. Antibodies were determined on days 0, 7, and 28 by hemagglutination inhibition. Univariate analysis was used to compare the immune response of dogs with HAC and healthy dogs. Pre-vaccination antibodies (≥10) were detected in 100% of dogs with HAC (11/11; 95% CI: 70.0–100) and in 93.5% of healthy dogs (29/31; 95% CI: 78.3–99.2). No ≥4-fold increase in antibody titer was observed in dogs with HAC while in 22.6% of healthy dogs, a ≥4-fold titer increase was observed (7/31; 95% CI: 11.1–40.1). Mild vaccine-associated adverse events (VAAEs) were detected in 54.5% of dogs with HAC (6/11; 95% CI: 28.0–78.8) and in 29.0% of healthy dogs (9/31; 95% CI: 15.9–46.8). There was neither a significant difference in presence of pre-vaccination antibodies (p = 1.000), or response to vaccination (p = 0.161), nor in the occurrence of VAAEs (p = 0.158). Immune function of dogs with HAC treated with trilostane seems comparable to that of healthy dogs.

Porcine Reproductive and Respiratory Syndrome Virus Promotes SLA-DR-Mediated Antigen Presentation of Nonstructural Proteins To Evoke a Nonneutralizing Antibody Response In Vivo.

The humoral immune response against porcine reproductive and respiratory syndrome virus (PRRSV) infection is characterized by a rapid induction of nonneutralizing antibodies (non-NAbs) against nonstructural proteins (NSPs). Here, we systematically investigated the potential mechanism for the induction of PRRSV NSP-specific non-NAbs. Our data suggested that PRRSV NSP-specific antibodies appeared within 10 days after PRRSV infection in vivo In the in vitro model, functional upregulation of swine leukocyte antigen (SLA)-DR was observed in bone marrow-derived dendritic cells (BMDCs) and porcine alveolar macrophages (PAMs), whereas remarkable inhibition at the mRNA level was observed after infection by both PRRSV-1 and PRRSV-2 isolates. Notably, the inconsistency in SLA-DR expression between the mRNA and protein levels resulted from deubiquitination of SLA-DR via the ovarian tumor (OTU) domain of PRRSV NSP2, which inhibited ubiquitin-mediated degradation. Moreover, mass spectrometry-based immunopeptidome analysis identified immunopeptides originating from multiple PRRSV NSPs within SLA-DR of PRRSV-infected BMDCs. Meanwhile, these PRRSV NSP-derived immunopeptides could be specifically recognized by serum from PRRSV-infected piglets. Notably, certain NSP-derived immunopeptides characterized in vitro could be identified from PAMs or hilar lymph nodes from PRRSV-infected piglets. More importantly, an in vitro neutralizing assay indicated that serum antibodies against NSP immunopeptides were unable to neutralize PRRSV in vitro Conversely, certain structural protein (SP)-derived immunopeptides were identified and could be recognize by pig hyperimmune serum against PRRSV, which further indicates that the NSP-derived antibody response is nonprotective in vivo In conclusion, our data suggested that PRRSV infection interferes with major histocompatibility complex class II (MHC-II) molecule-mediated antigen presentation in antigen-presenting cells (APCs) via promoting SLA-DR expression to present immunopeptides from PRRSV NSPs, which contributes to the induction of non-NAbs in vivoIMPORTANCE PRRSV has haunted the swine industry for over 30 years since its emergence. Besides the limited efficacy of PRRSV modified live vaccines (MLVs) against heterogeneous PRRSV isolates, rapid induction of nonneutralizing antibodies (non-NAbs) against PRRSV NSPs after MLV immunization or wild-strain infection is one of the reasons why development of an effective vaccine has been hampered. By using in vitro-generated BMDCs as models to understand the antigen presentation process of PRRSV, we obtained data indicating that PRRSV infection of BMDCs promotes functional SLA-DR upregulation to present PRRSV NSP-derived immunopeptides for evoking a non-NAb response in vivo Our work not only uncovered a novel mechanism for interference in host antigen presentation by PRRSV but also revealed a novel insight for understanding the rapid production of nonneutralizing antibodies against PRRSV NSPs, which may have benefit for developing an effective vaccine against PRRSV in the future.

Antiviral Strategies of Chinese Herbal Medicine Against PRRSV Infection.

Bioactive compounds from Traditional Chinese Medicines (TCMs) are gradually becoming an effective alternative in the control of porcine reproductive and respiratory syndrome virus (PRRSV) because most of the commercially available PRRSV vaccines cannot provide full protection against the genetically diverse strains isolated from farms. Besides, the incomplete attenuation procedure involved in the production of modified live vaccines (MLV) may cause them to revert to the more virulence forms. TCMs have shown some promising potentials in bridging this gap. Several investigations have revealed that herbal extracts from TCMs contain molecules with significant antiviral activities against the various stages of the life cycle of PRRSV, and they do this through different mechanisms. They either block PRRSV attachment and entry into cells or inhibits the replication of viral RNA or viral particles assembly and release or act as immunomodulators and pathogenic pathway inhibitors through cytokines regulations. Here, we summarized the various antiviral strategies employed by some TCMs against the different stages of the life cycle of PRRSV under two major classes, including direct-acting antivirals (DAAs) and indirect-acting antivirals (IAAs). We highlighted their mechanisms of action. In conclusion, we recommended that in making plans for the use of TCMs to control PRRSV, the pathway forward must be built on a real understanding of the mechanisms by which bioactive compounds exert their effects. This will provide a template that will guide the focus of collaborative studies among researchers in the areas of bioinformatics, chemistry, and proteomics. Furthermore, available data and procedures to support the efficacy, safety, and quality control levels of TCMs should be well documented without any breach of data integrity and good manufacturing practices.

Serodynamic Analysis of the Piglets Born from Sows Vaccinated with Modified Live Vaccine or E2 Subunit Vaccine for Classical Swine Fever.

Classical swine fever (CSF) caused by the CSF virus (CSFV) is one of the most important swine diseases, resulting in huge economic losses to the pig industry worldwide. Systematic vaccination is one of the most effective strategies for the prevention and control of this disease. Two main CSFV vaccines, the modified live vaccine (MLV) and the subunit E2 vaccine, are recommended. In Taiwan, CSF cases have not been reported since 2006, although systemic vaccination has been practiced for 70 years. Here, we examined the sero-dynamics of the piglets born from sows that received either the CSFV MLV or the E2 vaccine and investigated in the field the correlation between the porcine reproductive and respiratory syndrome virus (PRRSV) loads and levels of CSFV antibody. A total of 1398 serum samples from 42 PRRSV-positive farms were evaluated to determine the PRRSV loads by real-time PCR and to detect CSFV antibody levels by commercial ELISA. Upon comparing the two sow vaccination protocols (CSFV MLV vaccination at 4 weeks post-farrowing versus E2 vaccination at 4–5 weeks pre-farrowing), the lowest levels of CSFV antibody were found in piglets at 5–8 and 9–12 weeks of age for the MLV and E2 groups, respectively. Meanwhile, the appropriate time window for CSFV vaccination of offspring was at 5–8 and 9–12 weeks of age in the MLV and E2 groups, respectively. There was a very highly significant negative correlation between the PRRSV load and the level of CSFV antibody in the CSFV MLV vaccination group (P < 0.0001). The PRRSV detection rate in the pigs from the MLV group (27.78%) was significantly higher than that in pigs from the E2 group (21.32%) (P = 0.011). In addition, there was a significant difference (P = 0.019) in the PRRSV detection rate at 5–8 weeks of age between the MLV (42.15%) and E2 groups (29.79%). Our findings indicate that the vaccination of CSFV MLV in piglets during the PRRSV susceptibility period at 5–8 weeks of age may be overloading the piglet’s immune system and should be a critical concern for industrial pork production in the field.

In Vivo Demonstration of the Superior Replication and Infectivity of Genotype 2.1 with Respect to Genotype 3.4 of Classical Swine Fever Virus by Dual Infections.

In Taiwan, the prevalent CSFV population has shifted from the historical genotype 3.4 (94.4 strain) to the newly invading genotype 2.1 (TD/96 strain) since 1996. This study analyzed the competition between these two virus genotypes in dual infection pigs with equal and different virus populations and with maternally derived neutralizing antibodies induced by a third genotype of modified live vaccine (MLV), to simulate that occurring in natural situations in the field. Experimentally, under various dual infection conditions, with or without the presence of maternal antibodies, with various specimens from blood, oral and fecal swabs, and internal organs at various time points, the TD/96 had consistently 1.51−3.08 log higher loads than those of 94.4. A second passage of competition in the same animals further widened the lead of TD/96 as indicated by viral loads. The maternally derived antibodies provided partial protection to both wild type CSFVs and was correlated with lower clinical scores, febrile reaction, and animal mortality. In the presence of maternal antibodies, pigs could be infected by both wild type CSFVs, with TD/96 dominating. These findings partially explain the CSFV shift observed, furthering our understanding of CSFV pathogenesis in the field, and are helpful for the control of CSF.

Immune response and protective efficacy of intramuscular and intradermal vaccination with porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) modified live vaccine against highly pathogenic PRRSV-2 (HP-PRRSV-2) challenge, either alone or in combination with of PRRSV-1

The study was conducted to evaluate the immune response of pigs vaccinated intramuscularly (IM) or intradermally (ID) with porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) modified live vaccine (MLV). The protective efficacy was evaluated upon challenge with highly pathogenic (HP)-PRRSV-2, either alone or in combination with PRRSV-1. Forty-two, castrated male, PRRSV-free pigs were randomly allocated into 7 groups of 6 pig each. IM/HPPRRSV2, IM/CoChallenge, ID/HPPRRSV2 and ID/CoChallenge groups were vaccinated IM or ID with PRRSV-1 MLV (UNISTRAIN® PRRS, Laboratorios Hipra S.A., Amer, Spain) in accordance to the manufacturer’s directions. NV/HPPRRSV2 and NoVac/CoChallenge groups were nonvaccinated/challenged controls. NoVac/NoChallenge group was left as the control. Antibody response, IFN-γ-secreting cells (IFN-γ-SC) and IL-10 production were evaluated following vaccination. At 35 days post vaccination (DPV), all challenged groups were intranasally inoculated with HP-PRRSV-2, either alone or in combination with PRRSV-1. PRRSV viremia and lung lesion scores were evaluated following challenge. The results demonstrated that ID vaccinated pigs had significantly lower IL-10 levels and higher IFN-γ-SC than that of IM vaccinated pigs. Following challenge with HP-PRRSV-2 either alone or with PRRSV-1, PRRSV viremia and lung lesions, both macroscopically and microscopically, were significantly reduced in vaccinated pigs than that of nonvaccinated pigs, regardless to the route of vaccine administration. ID vaccinated pigs had significantly lower levels of PRRSV viremia and lung lesion scores than that of IM vaccinated pigs. The results of the study suggested that the administration of PRRSV-1 MLV, either IM or ID, provided partial protection against HP-PRRSV-2, either alone or when cochallenged with PRRSV-1, as demonstrated by the reduction in lung lesions and viremia. The ID route might represent an alternative to improve vaccine efficacy, as it resulted in lower IL-10 levels and higher IFN-γ-SC levels.

Comparison of whole genome sequences of Streptococcus equi subsp. equi from an outbreak in Texas with isolates from within the region, Kentucky, USA, and other countries

Strangles, caused by Streptococcus equi subspecies equi (S. equi) is an infectious disease of horses with worldwide distribution, but there are limited data available regarding strain variation using whole genome sequencing among and within outbreaks in the United States (US), and how US isolates compare with S. equi isolated globally. To address this knowledge-gap, we compared the whole genomes of 54 S. equi isolates from Texas and Kentucky and those of 230 publicly available sequences of S. equi isolates collected from other countries. Our results show that despite minimal variation among isolates within an outbreak some mutations do occur among individual outbreak isolates. Some S. equi strains from the US are closely related to S. equi isolates from other countries, likely reflecting international dissemination of isolates. Collectively, these data improve our understanding of phenotypic and genotypic variation of isolates within an outbreak, and the international distribution of S. equi. We also identify a novel variant of the S. equi M-protein, and observed cases of strangles that were caused by the modified-live vaccine but that were not recognized as vaccine-associated at the time of clinical sample submission.

Cell-mediated immune response and protective efficacy of porcine reproductive and respiratory syndrome virus modified-live vaccines against co-challenge with PRRSV-1 and PRRSV-2

Cell-mediated immunity (CMI), IL-10, and the protective efficacy of modified-live porcine reproductive and respiratory syndrome virus (PRRSV) vaccines (MLV) against co-challenge with PRRSV-1 and PRRSV-2 (HP-PRRSV) were investigated. Seventy, PRRSV-free, 3-week old, pigs were allocated into 7 groups. Six groups were intramuscularly vaccinated with MLV, including Porcilis (PRRSV-1 MLV, MSD Animal Health, The Netherlands), Amervac (PRRSV-1 MLV, Laboratorios Hipra, Spain), Fostera (PRRSV-2 MLV, Zoetis, USA), Ingelvac PRRS MLV and Ingelvac PRRS ATP (PRRSV-2, Boehringer Ingelheim, USA), and Prime Pac PRRS (PRRSV-2 MLV, MSD Animal Health, The Netherlands). Unvaccinated pigs were left as control. Lymphocyte proliferative response, IL-10 and IFN-γ production were determined. At 35 days post-vaccination (DPV), all pigs were inoculated intranasally with 2 ml of each PRRSV-1 (105.4 TCID50/ml) and PRRSV-2 (105.2 TCID50/ml, HP-PRRSV). Following challenge, sera were quantitatively assayed for PRRSV RNA. Pigs were necropsied at 7 days post-challenge. Viremia, macro- and microscopic lung lesion together with PRRSV antigen presence were evaluated in lung tissues. The results demonstrated that, regardless of vaccine genotype, CMI induced by all MLVs was relatively slow. Increased production of IL-10 in all vaccinated groups was observed at 7 and 14 DPV. Pigs in Amervac, Ingelvac MLV and Ingelvac ATP groups had significantly higher levels of IL-10 compared to Porcilis, Fostera and Prime Pac groups at 7 and 14 DPV. Following challenge, regardless to vaccine genotype, vaccinated pigs had significantly lower lung lesion scores and PRRSV antigens than those in the control group. Both PRRSV-1 and PRRSV-2 RNA were significantly reduced. Prime Pac pigs had lowest PRRSV-1 and PRRSV-2 RNA in serum, and micro- and macroscopic lung lesion scores (p < 0.05) compared to other vaccinated groups. In conclusion, PRRSV MLVs, regardless of vaccine genotype, can reduce viremia and lung lesions following co-challenge with PRRSV-1 and PRRSV-2 (HP-PRRSV). The main difference between PRRSV MLV is the production of IL-10 following vaccination.

A comparison of commercial modified-live PRRSV-1 and PRRSV-2 vaccines against a dual heterologous PRRSV-1 and PRRSV-2 challenge in late term pregnancy gilts

This study compared the efficacy, in terms of reproductive performance, of a porcine reproductive and respiratory syndrome virus (PRRSV)-1 or PRRSV-2 modified-live virus (MLV) vaccine against a dual heterologous PRRSV-1 and PRRSV-2 challenge. Gilts were administered either the PRRSV-1 or PRRSV-2 MLV vaccine at 21 days prior to breeding and were challenged intranasally with both PRRSV species at day 93 of gestation. Vaccination of gilts with PRRSV-2 MLV vaccine resulted in improved reproductive performance in sows (e.g. duration of pregnancy) and piglet health and overall viability (e.g. increase of the number of live-born and weaned pigs, and decrease of stillborn). Vaccination of gilts with PRRSV-1 MLV vaccine was able to reduce only PRRSV-1 viremia in contrast, PRRSV-2 MLV vaccine was able to reduce both PRRSV-1 and PRRSV-2 viremia. Vaccination of gilts with PRRSV-2 MLV induced higher numbers of PRRSV-2 specific interferon-γ secreting cells (IFN-γ-SC) compared to the PRRSV-1 MLV while there was no difference in the number of PRRSV-1 specific IFN-γ-SC between the two vaccines. Taken together, the results presented here suggest that vaccination of gilts with the PRRSV-2 MLV vaccine is more efficacious against dual heterologous PRRSV-1 and PRRSV-2 challenge compared to the PRRSV-1 MLV vaccine.

Efficacy Evaluation of Two Commercial Vaccines Against a Recombinant PRRSV2 Strain ZJnb16-2 From Lineage 8 and 3 in China.

From 2010, novel recombinant lineage 3 of porcine reproductive and respiratory syndrome virus 2 (PRRSV2) has continuously emerged China, which has brought about clinical outbreaks of the disease. Previously, a PRRSV2 strain named ZJnb16-2 was identified as a recombinant virus from lineage 8 and 3. In this study, two modified-live vaccines VR2332 MLV and HuN4-F112, which belong to lineage 5 and 8 respectively, were used for efficacy evaluation against the challenge of ZJnb16-2. Piglets vaccinated with HuN4-F112 exhibited temporary fever, higher average daily weight gain, and mild clinical signs as compared to VR2332 MLV vaccinated and unvaccinated piglets upon ZJnb16-2 challenge. Both vaccines could inhibit virus replication in piglets at 21days post challenge (DPC). Cross-reactivity of interferon (IFN)-γ secreting cells against ZJnb16-2 were detected in both vaccinated piglets. The number of IFN-γ secreting cells against ZJnb16-2 in the vaccination group exhibited sustaining elevation after challenge. Results demonstrated that both vaccines provided partial protection against ZJnb16-2 infection. A cross-neutralization antibody against ZJnb16-2 was not detected in any vaccinated piglet before challenge. A low neutralizing antibody titer against ZJnb16-2 was detected after challenge. Besides, all the vaccinated piglets suffered from different degrees of lung pathological lesions, indicating neither VR2332 MLV nor HuN4-F112 provided full protection against ZJnb16-2. This study provides valuable guidelines to control the recombinant virus from lineage 8 and 3 infection with MLV vaccines in the field.

Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I).

To investigate CTL epitope applications in swine, SLA-1*1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. First, nine predicted PRRSV peptides were tested by assembly of the peptide-SLA-1*1502 (pSLA-1*1502) complexes, and the crystal structure of the SLA-1*1502 complex with one peptide (NSP9-TMP9) was determined. The NSP9-TMP9 peptide conformation presented by pSLA-1*1502 is different from that of the peptides presented by the known pSLA-1*0401 and pSLA-3*hs0202 complexes. Two consecutive Pro residues make the turn between P3 and P4 of NSP9-TMP9 much sharper. The D pocket of pSLA-1*1502 is unique and is important for peptide binding. Next, the potential SLA-1*1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1*1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide. The tetrameric complex of SLA-1*1502 and NSP9-TMP9 was constructed and examined. Finally, taking NSP9-TMP9 as an example, the CTL immunogenicity of the identified PRRSV peptide epitope was evaluated. The SPF swine expressing the SLA-1*1502 alleles were divided into three groups: modified live vaccine (MLV), MLV+NSP9-TMP9, and the blank control group. NSP9-TMP9 was determined as a PRRSV CTL epitope with strong immunogenicity by flow cytometry and IFN-γ expression. Our study developed an integrated approach to identify SLA-I-restricted CTL epitopes from various important viruses and is helpful in designing and applying effective peptide-based vaccines for swine.

320 Carcass characteristics of Bos indicus-Bos taurus steers following BVDV type 1b challenge

Abstract Bovine Viral Diarrhea virus (BVDV), is a component of bovine respiratory disease (BRD) worldwide. Documentation of animal genetic influences and performance variability specific to BVDV challenge is limited. This study evaluated individual animal effects in the 14 d following BVDV Type 1b intranasal challenge in yearling, Nellore-Angus (Bos indicus-Bos taurus) F2 and F3 crossbred steers (n = 363) on carcass traits 180 d post-challenge. Prior to challenge steers were confirmed to be free of BVDV infection with families balanced across non-vaccinated control, killed (KV), or modified-live (MLV) commercial BRD vaccines. Hot carcass weight (HCW), adjusted fat thickness (AFT), longissimus muscle area (REA) and marbling score (MARB) were analyzed through mixed models with sire and pen(year) as random effects; potential fixed effects of vaccine, type of cross, pyrexia status, clinical sign presentation, and levels of feed intake and ADG 14 d post-challenge were investigated. Vaccine influenced AFT (P = 0.016); MLV steers had 0.26 cm less AFT than KV steers. Marbling was affected by type of cross (P = 0.023) with up to 0.60 marbling scores higher (P &amp;lt; 0.05) in some parental combinations; an interaction between type of cross and pyrexia status also affected MARB (P = 0.017) with one parental combination having higher MARB associated with pyrexia. Hot carcass weight was not affected by pyrexia, but was affected by feed intake (P = 0.019), with steers in the highest vs. lowest category averaging 24.0 kg heavier. No animals presented morbidity signs severe enough for therapeutic treatment, yet presence of mild clinical symptoms affected REA (P = 0.012), resulting in 3.4 cm2 lower REA, however, this pattern was inconsistent among feed intake levels. This study affirms the complexity of health impacts on beef carcass traits and the need for improved study of subclinical illness in beef production systems.

Efficacy of concurrent vaccination with modified-live PRRSV-1 and PRRSV-2 vaccines against heterologous dual PRRSV-1 and PRRSV-2 challenge in late term pregnancy gilts

The objective of this study was to evaluate the effect of concurrent vaccination with a porcine reproductive and respiratory syndrome virus (PRRSV)-1 modified-live virus (MLV) vaccine and a PRRSV-2 MLV vaccine against a dual heterologous PRRSV-1 and PRRSV-2 challenge in late term pregnancy gilts. Gilts were concurrently administered PRRSV-1 and PRRSV-2 MLV vaccines at 21 days prior to breeding at separate anatomical sites and were inoculated intranasally with both PRRSV types at 93 days of gestation. Vaccinated gilts had a higher number of live-born and weaned pigs, and a decrease in stillbirths compared to the unvaccinated control group following a dual challenge. Concurrent vaccination resulted also in the reduction of both PRRSV-1 and PRRSV-2 viremia which correlated with an increase in the number of PRRSV-1 and PRRSV-2 specific interferon-γ secreting cells (IFN-γ-SC). We believe the T cell responses contributed to the reduction of both PRRSV-1 and PRRSV-2 viremia. The results presented here demonstrate that concurrent vaccination with PRRSV-1 and PRRSV-2 MLV vaccines improves reproductive performance, reduces viremia of PRRSV-1 and PRRSV-2, and induces protective T cell reactions against dual PRRSV-1 and PRRSV-2 challenge in late term pregnancy gilts without local and systemic adverse reactions related to concurrent vaccination.

An immunomodulatory feed additive enhances in vitro viral vaccine recall antigen responses in dairy heifers

Enhancing immunological responses to vaccination is an important goal in many herd health management systems. OmniGen-AF®(OG) is an immunomodulatory feed additive that has been shown to enhance innate immune function in ruminants and its effects on adaptive immunity require additional study. The objective of this study was to evaluate post-vaccine antibody titers and circulating cellular memory development in heifers fed OG and administered a commercially available modified-live bovine respiratory disease (BRD) vaccine. Twenty-four Holstein heifers were assigned to one of two diets for 170 days: Control TMR (CON; n = 11), or TMR plus OG (TRT; 9 g/100 kg BW/day; n = 13). Samples for hematology, serology, and cellular assays were collected on D-110, 0, 21, 42, and 60 of the trial. Heifers were administered two priming doses of a modified-live BRD vaccine, with a third dose given on D0. There were no significant differences in total WBC and absolute number or the percentage of circulating lymphocytes, monocytes, neutrophils, RBC, or platelets on D-110 through D21. On D42 and D60, CON had significantly higher numbers of lymphocytes. On D0, mean serum neutralizing (SN) titer to BHV-1 was significantly higher for CON compared to TRT. SN titers were not significantly different between CON and TRT at any other time point for BHV-1, BVDV type 1, or BVDV type 2. TRT mounted a significantly stronger recall proliferative response to 0.5 multiplicity of infection (MOI) of BHV-1, BVDV type 1 and BVDV type 2 on D42 and D60; 0.25 MOI of BVDV type 1 on D21 and D42; and 0.25 MOI BVDV type 2 on D42 compared to CON. IL-4 production induced by 0.5 and 1.0 MOI BHV-1 (D42 and D60); 0.25 MOI of BVDV type 1 (D21); and 0.25 and 0.5 MOI of BVDV type 2 (D60) were significantly higher for TRT than CON. IL-17 production induced by 0.25 MOI of BVDV type 1 was significantly higher on D60 for TRT compared to CON. IFN-gamma and IL-10 were not significantly different between treatments. These data indicate feeding OG has a beneficial effect on responses to vaccine antigens in Holstein dairy heifers.

Immune memory induced by intranasal vaccination with a modified-live viral vaccine delivered to colostrum fed neonatal calves

Bovine respiratory disease (BRD) remains a major health problem despite extensive use of vaccines during the post-weaning period. Apparent vaccine failure is attributed, in part, to primary vaccination during the period of greatest risk for BRD, providing inadequate time for onset of protective immunity. The current study investigated whether intranasal (IN) vaccination of 3–6 week old calves with a modified-live viral (MLV) vaccine induced sufficient immune memory to prevent respiratory disease and accelerate onset of protective immunity 5 months later. Vaccine groups included naïve controls, a single IN vaccination at 3–6 weeks of age, primary IN vaccination at 6 months, and either an IN or subcutaneous (SC) booster vaccination at 6 months (n = 10/group). All calves were challenged with BHV-1 four days after vaccination at 6 months of age. Primary IN vaccination at 6 months did not significantly reduce clinical disease but significantly (P < 0.01) reduced virus shedding. A single IN vaccination at 3–6 weeks of age significantly (P < 0.05) reduced weight loss but did not reduce fever or virus shedding. Both IN and SC booster vaccinations, significantly (P < 0.01) reduced clinical disease but virus shedding was significantly (P < 0.001) reduced only by IN booster vaccination. Reduction in virus shedding was significantly (P < 0.01) greater following booster versus primary IN vaccination at 6 months. All vaccination regimes significantly (P < 0.01) reduced secondary bacterial pneumonia and altered interferon responses relative to naïve controls. Only IN booster vaccination significantly (P < 0.05) increased BHV-1 specific IgA in nasal secretions. These results confirm primary MLV IN vaccination at 3 to 6 weeks of age, when virus neutralizing maternal antibody was present, induced immune memory with a 5 month duration. This immune memory supported rapid onset of protective immunity four days after an IN booster vaccination.

Using commercial ELISAs to assess humoral response in sows repeatedly vaccinated with modified live porcine reproductive and respiratory syndrome virus

BackgroundSows in breeding herds are often mass vaccinated against porcine reproductive and respiratory syndrome (PRRS) every few months using modified live vaccines (MLV). Field veterinarians repeatedly report that multiple vaccinated...

Influence of a bovine respiratory disease vaccine with a temperature‐sensitive modified live or killed infectious bovine rhinotracheitis component on oestrous cycle parameters and anti‐Müllerian hormone concentration in nulliparous heifers

The objective of this study was to examine the impact of a bovine respiratory disease complex (BRDC) vaccine with a temperature-sensitivemodified live vaccine (MLV) infectious bovine rhinotracheitis (IBR) component on oestrous cycle parameters and the follicular pool. Twenty-four Holstein heifers (12.4±0.5months) previously calfhood vaccinated with an IBR MLV component were enrolled in two replicates (Spring; n=10 and Fall; n=14) and were blocked by pre-vaccination bovine viral diarrhoea (BVD) serum neutralizing (SN) titres. Upon enrolment, heifers were oestrous synchronized with sampling beginning at detected oestrus. At their second heat, heifers were vaccinated with a BRDC calfhood vaccine with a MLV (MLV; n=12) or killed (K; n=12) IBR component and sampled for two additional cycles. Serum samples for oestrogen (E2) and progesterone (P4) as well as ultrasound data of ovarian structures were collected every other day. Serum samples for anti-Müllerian hormone (AMH) were collected at oestrus and mid-cycle for each cycle, and serum for titres was collected prior to and following vaccination. Data were analysed with the PROC MIXED and GLM procedures of SAS. There was no difference in pre- or post-vaccination titres between MLV and K heifers (p>.5). Vaccination had no impact on P4 concentrations, P4 area under the curve, luteal tissue area, peak E2 production or oestrous cycle length (p>.05). Cycle number did impact AMH concentration (p<.05). In MLV heifers, AMH concentration was highest in cycle 1 (p<.05) while cycles 2 and 3 did not differ (p>.05). This was also true for the K heifers in the Fall replicate (p<.05). Within cycle 2, AMH concentrations were numerically lower between vaccine types (K=308.22±33.3pg/ml, MLV=181.13±32.9pg/ml; p>.05). Although no differences were seen in overall cycle parameters, differences in AMH concentrations may indicate a reduction of the follicular pool following vaccination andrequires further investigation.

Systematic review and meta-analysis comparing arrival versus delayed vaccination of high-risk beef cattle with 5-way modified-live viral vaccines against BHV-1, BRSV, PI3, and BVD types 1 and 2

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in North American beef cattle, and thus a major economic and welfare concern of individuals involved in the beef cattle industry. The most common viruses implicated in BRD are Bovine Herpesvirus 1 (BHV-1), Bovine Respiratory Syncytial Virus (BRSV), Parainfluenza 3 (PI3), and Bovine Viral Diarrhea Viruses types 1 and 2 (BVD 1 and 2), and it is common practice to administer vaccines against these viruses to cattle entering feedlots and stocker operations at arrival. However, there have long been concerns that cattle may not mount an optimal immune response when vaccinated at this time. A number of studies have been conducted to evaluate the effects of vaccination timing on morbidity and mortality, but often include other interventions that might confound interpretation of the results. This can make an objective evaluation of the effects of only vaccination timing difficult. It is therefore our goal to provide a systematic review of these studies, and extract relevant data to perform a meta-analysis of vaccine timing on BRD morbidity, retreatment rate, and mortality.

Effects of Intranasal Versus Intramuscular Modified Live Vaccines and Vaccine Timing on Health and Performance by Newly Received Beef Cattle

Two studies were conducted to evaluate the effects of viral vaccines and vaccination programs on health and performance of newly received beef cattle. In Exp. 1, two loads (120 steer and bull calves and 108 heifer calves for Load 1 and 2, respectively) were used to evaluate the effects of an intranasal vs an intramuscular IBR-PI3 vaccine on performance and health of newly received beef cattle. Treatments were: 1) no vaccine (Control); 2) an intranasal modified-live IBR-PI3 vaccine (IN); and 3) an intramuscular modified-live IBR-PI3 vaccine (IM). No treatment x load interactions were observed for performance data. For the 28-d receiving period, cattle given IN IBR-PI3 vaccine had greater daily gain (P &lt; .05) than cattle given IM IBR-PI3 vaccine. No differences (P &gt; .10) were noted for daily dry matter (DM) intake, however, the feed:gain ratio was increased (P &lt; .05) for the IM group as compared to the IN group. No differences (P &gt; .10) were noted among treatments in the percentage of cattle treated for BRD. In Exp. 2, 102 steer and bull calves were used to evaluate vaccine timing on health and performance of newly received calves. Treatments included: 1) no vaccine (Control); 2) no vaccine at processing, with an IM multiple antigen (IBR-PI3-BVD-BRSV) viral vaccine given on d 7; 3) intranasal IBR-PI3 administered at processing with IM IBR-PI3-BVD-BRSV vaccine given on d 7; and 4) IM IBR-PI3-BVD-BRSV vaccine administered both at processing and on d 7. No differences were noted for daily gain or daily DM intake during the 28-d receiving period. Feed:gain was improved (P &lt; .10) for vaccinated calves as compared to controls. Results suggest that an intranasal IBR-PI3 vaccine might have beneficial effects on gain and feed efficiency compared with an intramuscular IBR-PI:-i vaccine. There was no advantage or disadvantage to delaying vaccination with viral vaccines until 7 d after arrival. In terms of overall 28-d gains and morbidity, vaccines did not enhance gains or effect morbidity, compared to negative controls. However, statistical power to detect differences was marginal in both experiments.

Prevalence and genetic characteristics of porcine reproductive and respiratory syndrome virus in central China during 2016–2017: NADC30-like PRRSVs are predominant

NADC30-like strains of porcine reproductive and respiratory syndrome virus (PRRSV) were firstly reported in China in 2013. Since then, these strains have been epidemic in more than 13 provinces/regions. During 2016–2017, a total of 18 PRRSV isolates were obtained from 52 clinical samples in Henan province. Based on comparative and phylogenetic analyses of ORF5 and partial Nsp2 genes, 83.3% (15/18) isolates belonged to NADC30-like strains, and the ORF5 shared 87.4%–95.5% nucleotide identity with NADC30/JL580 and 84.2%–89.9% with JXA1/CH-1a, respectively. The genetic variation analysis showed that extensive amino acid substitutions happened in the significant regions of ORF5 including major linear antigenic epitopes (27-30aa, 37-45aa, 52-61aa) and the potential N-glycosylation sites (32-35aa). 16.7% (3/18) isolates were very close to HP-PRRSV derived attenuated strains. Moreover, these three isolates shared common residues at the positions 33D, 59 N, 164R, 196R in ORF5 and 303D, 399T, 575V, 598R, 604G in Nsp2, which were thought to be unique to modified live vaccines (MLVs) or their derivatives. Therefore, they were probably the revertants from MLVs. Our studies showed that the HP-PRRSV strains seemed to be gradually disappearing and NADC30-like strains had become the main causative agents of PRRS in central China. Comparing with HP-PRRSVs, the ORF5 of NADC30-like PRRSV strains displayed extensive amino acid mutations which may be related with immune evasion. Furthermore, the circulation of MLV derivatives in the fields made the diagnosis and control of PRRSV more complicated.