No vaccine interference between bovine coronavirus and bovine herpesvirus-1 in a randomized trial when coadministrating two intranasal modified-live viral vaccines to neonatal calves.

OBJECTIVE: Compare immune responses induced by 2 commercial intranasal (IN) modified-live viral (MLV) vaccines given individually or coadministered and evaluate prevention of infection and lung pathology following bovine herpesvirus-1 (BHV-1) challenge. ANIMALS: 36 male Holstein calves (ages, 5 to 12 days). METHODS: In a randomized complete block design, each calf received an IN injection of either vaccine diluent (Placebo), an MLV vaccine containing bovine herpesvirus-1 (BHV-1; N3), bovine coronavirus vaccine (BC), or both N3 and BC (BC + N3) with a booster 4 weeks later. Nasal secretions and blood were collected weekly. Three weeks after the booster, the calves were challenged with BHV-1, sampled for virus shedding, and euthanized 10 days later to quantify lung pathology. The study period was September 7, 2020, to April 6, 2021. RESULTS: Calves were seropositive for BHV-1 and BC before vaccination. No significant difference in BC-specific serum immunoglobin G and nasal immunoglobin A antibody responses in the BC versus BC + N3 group or BHV-1-specific serum immunoglobin G and nasal immunoglobin A antibody responses in the N3 versus BC + N3 group. Cytokine responses to BHV-1 and BC did not differ among groups. BHV-1 shedding after challenge was significantly reduced in N3 groups versus Placebo and BC. There was a significant reduction in lung pathology in the N3 + BC group versus Placebo. CLINICAL RELEVANCE: This study provides evidence an MLV vaccine containing BHV-1 and an MLV BC vaccine can be coadministered to neonatal calves without significantly altering immune responses to the 2 viruses or compromising the prevention of BHV-1 respiratory disease. Calves receiving the BC + N3 vaccine had a significant reduction in lung pathology after BHV-1 aerosol challenge.

How density dependence, genetic erosion and the extinction vortex impact evolutionary rescue.

Following severe environmental change that reduces mean population fitness below replacement, populations must adapt to avoid eventual extinction, a process called evolutionary rescue. Models of evolutionary rescue demonstrate that initial size, genetic variation and degree of maladaptation influence population fates. However, many models feature populations that grow without negative density dependence or with constant genetic diversity despite precipitous population decline, assumptions likely to be violated in conservation settings. We examined the simultaneous influences of density-dependent growth and erosion of genetic diversity on populations adapting to novel environmental change using stochastic, individual-based simulations. Density dependence decreased the probability of rescue and increased the probability of extinction, especially in large and initially well-adapted populations that previously have been predicted to be at low risk. Increased extinction occurred shortly following environmental change, as populations under density dependence experienced more rapid decline and reached smaller sizes. Populations that experienced evolutionary rescue lost genetic diversity through drift and adaptation, particularly under density dependence. Populations that declined to extinction entered an extinction vortex, where small size increased drift, loss of genetic diversity and the fixation of maladaptive alleles, hindered adaptation and kept populations at small densities where they were vulnerable to extinction via demographic stochasticity.

Fires slow population declines of a long-lived prairie plant through multiple vital rates.

In grasslands worldwide, modified fire cycles are accelerating herbaceous species extinctions. Fire may avert population declines by increasing survival, reproduction, or both. Survival and growth after fires may be promoted by removal of competitors or biomass and increasing resource availability. Fire-stimulated reproduction may also contribute to population growth through bolstered recruitment. We quantified these influences of fire on population dynamics in Echinacea angustifolia, a perennial forb in North American tallgrass prairie. We first used four datasets, 7-21 years long, to estimate fire's influences on survival, flowering, and recruitment. We then used matrix projection models to estimate growth rates across several burn frequencies in five populations, each with one to four burns over 15 years. Finally, we estimated the contribution of fire-induced changes in each vital rate to changes in population growth. Population growth rates generally increased with burning. The demographic process underpinning these increases depended on juvenile survival. In populations with high juvenile survival, fire-induced increases in seedling recruitment and juvenile survival enhanced population growth. However, in populations with low juvenile survival, small changes in adult survival drove growth rate changes. Regardless of burn frequencies, our models suggest populations are declining and that recruitment and juvenile survival critically influence population response to fire. However, crucially, increased seedling recruitment only increases population growth rates when enough new recruits reach reproductive maturity. The importance of recruitment and juvenile survival is especially relevant for small populations in fragmented habitats subject to mate-limiting Allee effects and inbreeding depression, which reduce recruitment and survival, respectively.

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.

Inhibition of priming for bovine respiratory syncytial virus-specific protective immune responses following parenteral vaccination of passively immune calves.

The effect of maternal antibodies (MatAb) on immunological priming by neonatal parenteral vaccination for bovine respiratory syncytial virus (BRSV) was addressed for the first time in experimental infection in 34 Holstein calves. Both vaccinated and control calves developed moderate to severe respiratory disease characteristic of acute BRSV infection. There were no differences in clinical signs, BRSV shed, arterial oxygen concentrations, or mortality between vaccinated and control calves after BRSV challenge approximately 11 wk after vaccination. There were no anamnestic antibody or cytokine responses in the vaccinates after challenge. Lung lesions were extensive in both groups, and although there was a statistically significant (P = 0.05) difference between groups, this difference was considered not biologically significant. These data indicate that stimulation of protective immune responses was inhibited by maternal antibodies when a combination modified-live BRSV vaccine was administered parenterally to young passively immune calves. Alternate routes of administration or different vaccine formulations should be used to successfully immunize young calves with good passive antibody transfer.

Inhibition de l'amorçage pour les réponses immunitaires protectrices spécifiques pour le virus respiratoire syncytial bovin après la vaccination parentérale des veaux ayant une immunité passive. L'effet des anticorps maternels sur l'amorçage immunologique par une vaccination parentérale néonatale pour le virus respiratoire syncytial bovin (VRS) a été abordé pour la première fois dans une infection expérimentale chez 34 veaux Holstein. Les veaux vaccinés et témoins ont développé une maladie respiratoire de modérée à grave présentant les caractéristiques d'une infection aiguë au VRS. Il n'y avait pas de différences au niveau des signes cliniques, de l'excrétion du VRS, des concentrations d'oxygène artérielle ou de la mortalité entre les veaux vaccinés et témoins après un test de provocation de VRS, environ 11 semaines après le vaccin. Il n'y avait aucune réponse d'anticorps ou de cytokines anamnestiques chez les veaux vaccinés après le test de provocation. Les lésions aux poumons étaient importantes dans les deux groupes et, même s'il y avait une différence statistiquement significative (P = 0,05) entre ces groupes, cette différence n'était pas considérée significative sur le plan biologique. Ces données indiquent que la stimulation des réponses immunitaires protectrices a été inhibée par les anticorps maternels lors de l'administration parentérale d'une combinaison de vaccin à VRS vivant modifié aux jeunes veaux ayant une immunité passive. D'autres voies d'administration ou différentes formulations de vaccins devraient être utilisées pour immuniser avec succès les jeunes veaux ayant un bon transfert passif.(Traduit par Isabelle Vallières).

Effect of calf age and administration route of initial multivalent modified-live virus vaccine on humoral and cell-mediated immune responses following subsequent administration of a booster vaccination at weaning in beef calves.

OBJECTIVE: To compare immune responses following modified-live virus (MLV) vaccination at weaning after intranasal or SC administration of an MLV vaccine to beef calves at 2 or 70 days of age. ANIMALS: 184 calves. PROCEDURES: Calves were allocated to 1 of 5 groups. The IN2 (n = 37) and IN70 (37) groups received an MLV vaccine containing bovine herpesvirus 1 (BHV1), bovine viral diarrhea virus (BVDV) types 1 and 2, bovine respiratory syncytial virus (BRSV), and parainfluenza 3 virus intranasally and a Mannheimia haemolytica and Pasteurella multocida bacterin SC at median ages of 2 and 70 days, respectively. The SC2 (n = 36) and SC70 (37) groups received a 7-way MLV vaccine containing BHV1, BVDV1, BVDV2, BRSV, parainfluenza 3 virus, M haemolytica, and P multocida SC at median ages of 2 and 70 days, respectively; the control group (37) remained unvaccinated until weaning. All calves received the 7-way MLV vaccine SC at median ages of 217 (weaning) and 231 days. Serum neutralizing antibody (SNA) titers against BHV1, BVDV1, and BRSV and intranasal IgA concentrations were determined at median ages of 2, 70, 140, 217, and 262 days. Cell-mediated immunity (CMI) against BHV1, BRSV, BVDV1, and P multocida was determined for 16 calves/group. RESULTS: At median ages of 140 and 217 days, BVDV1 SNA titers were significantly higher for the SC70 group than those for the other groups. Intranasal IgA concentrations and CMI increased over time for all groups. Vaccination at weaning increased SNA titers and CMI in all groups. CONCLUSIONS AND CLINICAL RELEVANCE: SC administration of an MLV vaccine to 70-day-old calves significantly increased BVDV1 antibody titers before weaning.

Reproductive safety of vaccination with Vista 5 L5 SQ near breeding time as determined by the effect on conception rates.

Replacement heifers (N=799; 10 to 13 months of age) were vaccinated with Vista 5 L5 SQ (Intervet; a reconstituted vaccine-bacterin product containing modified-live cultures of infectious bovine rhinotracheitis [IBR] virus, bovine viral diarrhea virus [BVDV; types 1 and 2], parainfluenza-3 virus, and bovine respiratory syncytial virus and inactivated cultures of Leptospira serovars canicola, grippotyphosa, hardjo, icterohaemorrhagiae, and pomona with a proprietary adjuvant) at either 40 plus/minus 5 days (control; n=399) or 3 days (test; n=400) before peak breeding day. By 40 plus/minus 5 days before peak breeding day, heifers in both groups had greater average titers to IBR, BVDV types 1 and 2, and four of the five Leptospira antigens assessed as compared with prevaccination titers on day -90 plus/minus 25 days. Conception rates were not affected by treatment. This study suggests that conception rates will not differ between heifers vaccinated with Vista 5 L5 SQ 3 days before breeding and those vaccinated approximately 40 days before breeding.

Treatment of medium-sized juxtapapillary melanoma with external Co-60 photon therapy.

Twenty-six patients with medium-sized juxtapapillary choroidal melanomas were irradiated using D-shaped Co-60 beams. The overall 5-year actuarial survival was 86% with a trend towards better 5-year local control with 70 vs. 60 Gy (100 vs. 75%). Of patients with pre-treatment > or =20/200 visual acuity, 37% had functional vision at 5 years.