Modified-live Vaccine Research Articles

Case report

Bovine viral diarrhea virus (BVDV) continues to be a challenge for the cattle industry despite routine vaccination that includes killed or modified-live BVDV antigens. At a commercial dairy, 1,081 newborn calves were tested for BVDV antigen by pooled reverse transcription polymerase chain reaction as part of a screening program. Immunohistochemistry confirmed persistent BVDV infections in 13 calves. Ten of the PI calves were available for BVD typing. Both cytopathic and non-cytopathic BVD viruses were isolated. The non-CPE viruses typed as BVD type lb with a total of 3 different strains found; an identical strain found in 2 calves, another identical strain found in 2 other calves, and a third identical strain found in 3 other calves. A BVDV control program relying solely on BVD vaccination using a modified-live vaccine did not protect calves in this herd from persistent infection with type lb BVDV. These results demonstrate that control programs that rely only on vaccination to control BVDV without testing for the presence of PI animals are not adequate to control BVD.

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 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.

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.

Control and eradication of porcine reproductive and respiratory syndrome virus type 2 using a modified-live type 2 vaccine in combination with a load, close, homogenise model: an area elimination study

BackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) causes significant animal and economic losses worldwide. The infection is difficult to control and PRRSV elimination at local level requires coordinated intervention among multiple farms. This case study describes a successful elimination of PRRSV from all 12 herds on the Horne Peninsula, Denmark, using a combination of load, close, homogenise (LCH) using PRRSV type 2 modified-live vaccine, optimised pig flow, and’10 Golden Rules’ (10GR) for biosecurity management. To the authors’ knowledge, this is the first successful European PRRSV area elimination project documented in detail. The PRRSV type 2 modified-live vaccine was used as part of the LCH method in breeding herds. Complete or partial depopulation was performed in some infected herds. A simplified biosecurity protocol (10GR) based on the McREBEL™ system of pig flow management, was employed in all herds and at all times throughout the study.ResultsAt study commencement, all herds were infected with PRRSV, and most were actively shedding virus. In just over 18 months, all 12 herds on the Horne Peninsula were confirmed to be PRRSV negative by polymerase chain reaction testing and negative for antibodies against PRRSV by enzyme–linked immunosorbent assay testing. All herds were subsequently obtained ‘Specific Pathogen Free’ status for PRRSV.ConclusionsThis study provides compelling evidence suggesting that an area elimination plan combining LCH with PRRSV type 2 vaccination, optimised pig flow, and 10GR for biosecurity management can effectively eliminate PRRSV from a geographic area. Additionally this study confirms the value of a previously unpublished, simplified alternative to the McREBEL system for controlling PRRSV.

Interleukin-1 receptor antagonist: an early immunomodulatory cytokine induced by porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) infection poorly induces pro-inflammatory cytokines (IL-1, IL-6 and TNF-α) and type I IFN production during the early phase of infection. Our microarray analysis indicated strong upregulation of the IL1RA gene in type 2 PRRSV -infected monocyte-derived dendritic cells. Interleukin-1 receptor antagonist (IL-1Ra) is an early inhibitory cytokine that suppresses pro-inflammatory cytokines and T-lymphocyte responses. To investigate the induction of IL-1Ra by PRRSV, monocyte-derived dendritic cells were cultured with type 2 PRRSV or other swine viruses. PRRSV increased both IL1RA gene expression and IL-1Ra protein production in the culture. The enhanced production of IL-1Ra was further confirmed in PRRSV-cultured PBMC and PRRSV-exposed pigs by flow cytometry. Myeloid cell population appeared to be the major IL-1Ra producer both in vitro and in vivo. In contrast to the type 2 PRRSV, the highly pathogenic (HP)- PRRSV did not upregulate IL1RA gene expression in vitro. To determine the kinetics of PRRSV-induced IL1RA gene expression in relation to other pro-inflammatory cytokine genes, PRRSV-negative pigs were vaccinated with a commercially available type 2 modified-live PRRS vaccine or intranasally inoculated with HP-PRRSV. In modified-live PRRS vaccine pigs, upregulation of IL1RA, but not IL1B and IFNA, gene expression was observed from 2 days post- vaccination. Consistent with the in vitro findings, upregulation of IL1RA gene expression was not observed in the HP-PRRSV-infected pigs throughout the experiment. This study identified IL-1Ra as an early immunomodulatory mediator that could be involved in the immunopathogenesis of PRRSV infections.

Faecal shedding of canine parvovirus after modified-live vaccination in healthy adult dogs

Since little is known about the persistence and faecal shedding of canine parvovirus (CPV) in dogs after modified-live vaccination, diagnostic tests for CPV can be difficult to interpret in the post-vaccination period. The primary aim of this study was to determine the incidence, duration and extent of CPV vaccine virus shedding in adult dogs and to investigate related factors, including the presence of protective antibodies, increase in anti-CPV antibody titres and development of any gastrointestinal side-effects. A secondary objective was to assess prevalence of CPV field virus shedding in clinically healthy dogs due to subclinical infections. One hundred adult, healthy privately owned dogs were vaccinated with a commercial CPV-2 modified-live vaccine (MLV). Faeces were tested for the presence of CPV DNA on days 0 (prior to vaccination), 3, 7, 14, 21 and 28 by quantitative real-time PCR. Pre- and post-vaccination serum titres were determined by haemagglutination inhibition on days 0, 7 and 28.Transient excretion of CPV DNA was detected in 2.0% of dogs before vaccination. About one quarter of dogs (23.0%) shed CPV DNA during the post-vaccination period, but field and vaccine virus differentiation by VP2 gene sequencing was only successful in few samples. Faecal CPV excretion occurred despite protective serum antibody titres. Post-vaccination CPV shedding was not related to adequate antibody response after vaccination or to the occurrence of gastrointestinal side-effects. Despite individual differences, CPV DNA was detectable for up to 28 days after vaccination, although the faecal CPV DNA load in these clinically healthy dogs was very low.

Current concepts in dairy cattle vaccinology

Vaccination is an important component for the prevention and control of disease in the dairy herd. Modified-live vaccines (MLV) have been used because of the good antibody response, longer duration of immunity, fewer doses needed per animal, and lower cost. N on-adjuvanted MLV vaccines fail to booster well-vaccinated animals, as active vaccine-induced immunity neutralizes vaccine virus preventing the MLV from replicating and preventing a booster immune response. Improved adjuvants have increased the scope and duration of inactivated virus immunity. Prepartum vaccination aimed at colostrum development is critical. Inactivated viral vaccines aimed at reproductive disease have greatly improved and should be considered to be given in the dry period to provide maximum conception rate during the fresh period. The periparturient period (the last 3 weeks prior to calving and the first 3 weeks following calving) are poor times to initiate an immune response-hormonal, dietary and metabolic factors limit immune responsiveness. Post-partum is also a difficult time to vaccinate, as lactation energy demand supersedes immunity. Each vaccine program needs to be designed based on animal flow, actual "disease" threats, and labor on the farm.

Evaluation of a 20 year old porcine reproductive and respiratory syndrome (PRRS) modified live vaccine (Ingelvac® PRRS MLV) against two recent type 2 PRRS virus isolates in South Korea

Type 2 porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) was first isolated in Korea in 1994. The commercial PRRS modified live vaccine (Ingelvac® PRRS MLV, Boehringer Ingelheim Vetmedica Inc., St. Joseph, Missouri, USA) based on type 2 PRRSV, was first licensed for use in 3- to 18-week-old pigs in Korea in 1996. The objective of the present study was to evaluate the efficacy of this 20year old commercial PRRS modified live vaccine (MLV) against two recent PRRSV isolates. Two genetically distant type 2 PRRSV strains (SNUVR150004 for lineage 1 and SNUVR150324 for lineage 5), isolated in 2015, were used as challenge virus. Regardless of the challenge virus, vaccination of pigs effectively reduced the level of viremia, the lung lesions, and of the PRRSV antigen within the lung lesions. The induction of virus-specific interferon-γ secreting cells by the PRRS vaccine produced a protective immune response, leading to the reduction of PRRSV viremia. There were no significant differences in efficacy against the two recently isolated viruses by the PRRS MLV based on virological results, immunological responses, and pathological outcomes. This study demonstrates that the PRRS MLV used in this study is still effective against recently isolated heterologous type 2 PRRSV strains even after 20 years of use in over 35 million pigs

Bovine herpesvirus-1: Genetic diversity of field strains from cattle with respiratory disease, genital, fetal disease and systemic neonatal disease and their relationship to vaccine strains

Bovine herpesvirus-1 (BoHV-1) causes disease in cattle with varied clinical forms. In the U.S. there are two BoHV1 subtypes, BoHV-1.1 and BoHV-1.2b. Control programs in North America incorporate modified live (MLV) or killed (KV) viral vaccines. However, BoHV-1 strains continue to be isolated from diseased animals or fetuses after vaccination. It is possible to differentiate BoHV-1 wild-type from MLV vaccine strains by determining their single nucleotide polymorphism (SNP) patterns through either whole-genome sequencing or PCR sequencing of genomic regions containing vaccine-defining SNPs. To determine the BoHV-1 subtype in clinical isolates and their relationship to MLV strains, 8 isolates from varied clinical disease at three different laboratories in the U.S. were sequenced and phylogenetically analyzed. Five samples were isolated within the past 5 years from New York and 3 were archived samples recovered 35 years prior from Oklahoma and Louisiana. Based on phylogenetic analysis, four of the cases appeared to be due to an MLV vaccine: 3 cases of aborted fetuses and one neonate with systemic BoHV-1 disease. One aborted fetus was from a herd with no reported history of MLV vaccination in two years. The remaining four isolates did not group with any MLV vaccines: two were associated with bovine respiratory disease, one with vulvovaginitis, and a fourth was determined to be a BoHV-1.2b respiratory isolate. Recovery of BoHV-1.1 that is very closely related to an MLV vaccine virus from a herd not receiving vaccines in an extended period prior to its isolation suggests that MLV viruses may remain latent or circulate within herds for long periods.

Detection and differentiation of wild-type and a vaccine strain of Streptococcus equi ssp. equi using pyrosequencing

Streptococcus equi subspecies equi (S. equi), the causative agent of strangles, is an important equine pathogen. Strangles is a highly contagious disease and a commercial modified live vaccine (MLV) is used for protection, which although effective, may also result in clinical signs of the disease. A rapid means to differentiate between the MLV and wild-type infection is crucial for quarantine release and limiting the disease spread. This study describes the use of a pyrosequencing assay targeting a single nucleotide deletion upstream of the SzPSe gene to distinguish between the wild-type and vaccine strains. A set of 96 characterized clinical specimens and isolates were tested using the assay. The assay was successful in differentiating between wild-type S. equi and the vaccine strains and in discriminating S. equi from other Streptococci. The vaccine strain was identified in 61.7% (29/47) of the strangles cases in horses with a history of MLV vaccination.

Modified-live PRRSV subtype 1 vaccine UNISTRAIN® PRRS provides a partial clinical and virological protection upon challenge with East European subtype 3 PRRSV strain Lena.

BackgroundWestern European porcine reproductive and respiratory syndrome virus (PRRSV) strains cause limited and mild clinical signs whereas more virulent strains are circulating in Eastern Europe. The emergence of such highly virulent strains in Western Europe might result in severe clinical problems and a financial disaster. In this context, the efficacy of the commercial modified-live PRRSV subtype 1 vaccine UNISTRAIN® PRRS was tested upon challenge with the East European subtype 3 PRRSV strain Lena.ResultsThe mean duration of fever was shortened and the number of fever days was significantly lower in vaccinated pigs than in control pigs. Moreover, a lower number of vaccinated animals showed fever, respiratory disorders and conjunctivitis. The mean virus titers in the nasal secretions post challenge (AUC) were significantly lower in the vaccinated group than in the control group. The duration of viremia was slightly shorter (not significantly different) in the vaccinated group as compared to the control group.ConclusionsVaccination of pigs with the modified-live vaccine UNISTRAIN® PRRS provides a partial clinical and virological protection against the PRRSV subtype 3 strain Lena.

An experimental study with a vaccine strain of porcine reproductive and respiratory syndrome virus to determine effects on viremia assessed by reverse transcriptase-polymerase chain reaction in pigs fed rations medicated with tilmicosin or non-medicated

Objectives: To determine if feed medicated with tilmicosin affects viremia (assessed using reverse transcriptase-polymerase chain reaction [RT-PCR]) in pigs exposed to a vaccine strain of porcine reproductive and respiratory syndrome virus (PRRSV), clinical signs associated with vaccination (body temperature), and average daily gain. Materials and methods: Purebred Yorkshire pigs (N = 192) were each assigned to one of five treatment groups. Groups 1a and 1b remained PRRSV-negative (controls), while Groups 2, 3, and 4 were injected with a modified-live (MLV) PRRSV vaccine. Groups 1b and 2 were fed non-medicated feed. Rations contained tilmicosin at 400 mg per kg for Group 1a and Group 4 and 200 mg per kg for Group 3. Blood samples were collected to measure serum tilmicosin concentrations and assess PRRSV viremia. Bronchoalveolar lavage was performed and macrophages assessed for PRRSV viremia and tilmicosin concentrations. Results: Groups 1a and 1b remained PRRSV-negative. Number of PRRSV copies per mL in serum was highest in inoculated pigs at 10 days post inoculation, but did not differ among the three inoculated groups. Average daily gain (ADG) was higher in groups fed rations containing 400 mg per kg tilmicosin than in groups on non-medicated rations. Clinical signs of disease were absent in all pigs. Implications: Viremia associated with an MLV vaccine strain of PRRSV does not differ between pigs fed rations containing 200 or 400 mg per kg of tilmicosin. In the absence of clinical disease, pigs consuming tilmicosin-medicated feed have higher ADG than pigs consuming non-medicated feed.

One year duration of immunity of the modified live bovine viral diarrhea virus type 1 and type 2 and bovine herpesvirus-1 fractions of Vista® Once SQ vaccine

Three studies were performed to determine the duration of immunity of the bovine viral diarrhea virus type 1 and type 2 (BVDV-1 and BVDV-2) and bovine herpesvirus-1 (BHV-1) fractions of a commercially prepared modified-live vaccine. Vista® Once SQ (Vista®) vaccine contains five modified-live viruses, BVDV-1, BVDV-2, BHV-1, bovine respiratory syncytial virus, and bovine parainfluenza 3 virus, and two modified-live bacteria, Pasteurella multocida and Mannheimia haemolytica. For all three studies, calves were administered a single dose of vaccine or placebo vaccine subcutaneously, and were challenged with one of the three virulent viruses at least one year following vaccination. Calves were evaluated daily following challenge for clinical signs of disease associated with viral infection, nasal swab samples were evaluated for virus shedding, and serum was tested for neutralizing antibodies. Following the BVDV-1 and BVDV-2 challenges, whole blood was evaluated for white blood cell counts, and for the BVDV-2 study, whole blood was also evaluated for platelet counts. Calves vaccinated with BVDV type 1a, were protected from challenge with BVDV type 1b, and had significant reductions in clinical disease, fever, leukopenia, and virus shedding compared to control calves. Vaccinated calves in the BVDV-2 study were protected from clinical disease, mortality, fever, leukopenia, thrombocytopenia, and virus shedding compared to controls. Vaccinated calves in the BHV-1 study were protected from clinical disease and fever, and had significantly reduced duration of nasal virus shedding. These three studies demonstrated that a single administration of the Vista® vaccine to healthy calves induces protective immunity against BVDV-1, BVDV-2 and BHV-1 that lasts at least one year following vaccination.

Utility of two modified-live virus canine distemper vaccines in wild-caught fishers (Martes pennanti)

Background: Canine distemper virus (CDV) infects families in the order Carnivora. As a preventive measure, vaccinations against CDV are frequently given to mustelids in captive environments.Objectives: Our objectives were to compare the utility between two modified-live virus canine distemper vaccines (MLV CDV's), Fervac-D® (no longer manufactured) and Galaxy-D® (now manufactured by MSD Animal Health as part of a multivalent vaccine), in developing an immune response in wild-caught fishers.Animals and methods: The Pennsylvania Fisher Reintroduction Project (PFRP) used 14 wild-caught fishers during one year of the project to evaluate the utility of vaccinations against CDV as part of any reintroduction project. Fishers were injected subcutaneously in the nape of the neck with their designated vaccine.Results: Fervac-D® did not effectively stimulate development of a serologic antibody response, whereas Galaxy-D® had adequate seroconversion or rise of titer levels to suggest that the general use of MLV CDV may be suitable in fishers pending further studies.Conclusion: We recommend that future studies be conducted, evaluating the use of currently produced vaccines in fishers. Future research should also focus on the length of days required between administration of primary and booster vaccines to achieve sufficient immune response.Clinical importance: If only primary doses are required, then hard-release reintroduction projects for fishers could be recommended. If primary and booster vaccines are required then soft-release reintroduction projects should be recommended that include captive management periods, allowing for appropriate vaccination intervals needed to maximize the probability of protection against CDV.

Prevalence of antibodies to canine parvovirus and reaction to vaccination in client-owned, healthy dogs

The purpose of this population-based cohort study was to assess current prevalence of antibodies to canine parvovirus (CPV) in adult, healthy dogs, including risk factors associated with lack of antibodies,...

High definition viral vaccine strain identity and stability testing using full-genome population data – The next generation of vaccine quality control

BackgroundVaccines are the most effective prophylactic public health tools. With the help of vaccines, prevention of infectious disease spread and, in concert with other measures, even eradication has become possible. Until now, licensing and quality control require the determination of consensus genome sequences of replication competent infectious agents contained in vaccines. Recent improvements in sequencing technologies now enable the sequencing of complete genomes and the genetic analysis of populations with high reliability and resolution. The latter is particularly important for RNA viruses, which consist of fluctuating heterogeneous populations rather than genetically stable entities. This information now has to be integrated into the existing regulatory framework, challenging both licensing authorities and vaccine producers to develop new quality control criteria. MethodsCommercially available modified-live oral rabies vaccines and their precursor strains were deep-sequenced to assess strain identity and relations between strains based on population diversity. Strain relations were inferred based on the Manhattan distances calculated between the compositions of the viral populations of the strains. ResultsWe provide a novel approach to assess viral strain relations with high resolution and reliability by deep sequencing with subsequent analysis of the overall genetic diversity within the viral populations. A comparison of our novel approach of inferring strain relations based on population data with consensus sequence analysis clearly shows that consensus sequence analysis of diverse viral populations can be misleading. Therefore, for quality control of viral vaccines deep sequencing analysis is to be preferred over consensus sequence analysis. ConclusionsThe presented methodology allows for routine integration of deep sequencing data in vaccine quality control and licensing for highly reliable assessment of strain identity and stability.

Designing effective calf vaccination programs

Vaccination is an important component for the prevention and control of bovine bacterial and viral diseases. Modified-live vaccines (MLV) have been used because of the good antibody response, longer duration of immunity, fewer doses needed per animal, and lower cost. The selective pressure from an animal’s immune response may lead to new viruses that persist and cause problems in the herd. An interesting vaccine will be the live Pasteurella multicida and Mannheimia hemolytica vaccines. Non-adjuvanted MLV vaccines also fail to booster well vaccinated animals as active vaccine-induced immunity neutralizes vaccine virus preventing the MLV from replicating and preventing a booster immune response. Improved adjuvants have increased the scope and duration of inactivated virus immunity. Inactivated vaccines generate cell-mediated response and can enhance the immune response in well-vaccinated animals. This whole process from vaccination to achieving mature immune response takes at least 3 weeks. This fully developed mature primary response can then be boosted to get a true anamnestic secondary response. There is no "single vaccination program” that will work on most farms or ranches. Each vaccine program needs to be designed based on the actual threats and needs of the farm, and not based on a company’s or neighbors suggested program.

Effect of injectable trace minerals (zinc, manganese, selenium, and copper) on the humoral and cell-mediated immune responses to vaccine antigens following administration of a modified-live viral vaccine in dairy calves

The benefits of administering injectable trace minerals (ITM; Zn, Mn, Cu, and Se) on animal health and performance have been previously assessed in dairy and beef cattle. Previous studies demonstrated that ITM improved humoral immune response to bovine herpesvirus l(BHV-l) following administration of a modified live virus (MLV) vaccine in cattle. The objective of this study was to evaluate the effect of an ITM supplement containing zinc, manganese, selenium, and copper on the humoral and cell mediated immune (CMI) responses to individual vaccine antigens in dairy calves receiving a MLV vaccine containing bovine viral diarrhea virus (BVDV), BHV1, parainfluenza virus 3 (PI3V), and bovine respiratory syncytial virus (BRSV).

Phylodynamic analysis of the canine distemper virus hemagglutinin gene.

BackgroundCanine distemper (CD) is one of the most contagious and lethal viral diseases in dogs. Despite the widespread use of vaccines, the prevalence of the CD virus (CDV) has increased at an alarming rate in recent years. In this phylodynamic study, we investigated the spatiotemporal modes of dispersal, viral demographic trends, and effectiveness of vaccines for CDV. A total of 188 full-length CDV hemagglutinin (H) gene sequences dataset were subjected to recombination analysis, including seven from modified live vaccine (MLV) strains and 12 from Taiwan specimens. After excluding the MLV strains and potential recombinant strains, alignments of 176 of 188 previous CDV strains were further used to analyze phylodynamic characteristics, and evidence of selection, and co-evolution.ResultsThe CDV genotype consisted of MLV-associated genotypes such as America-1 and Rockborn-like strains, which were characterized by long terminal branches and no distinct geographical patterns among lineages. In contrast, wild-type isolates clustered into lineages with a spatiotemporal structure and short terminal branches. Co-circulation and extensive diversification were simultaneously observed. The sequence variation signature was shaped by both geographic diversity and host tropism. Codon 506 was identified as a multi-epistatic interacting in the H protein.ConclusionsThe topological signature revealed in this study suggests different epidemic scenarios. For example, a ladder-like backbone is a hallmark of directional selection, and cladogenesis at long terminal branches indicates the emergence of a surviving lineage. The stable effective viral population of CDV indicate the effectiveness of vaccines currently used to control the virus.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-015-0491-9) contains supplementary material, which is available to authorized users.