Immunogenicity and Vaccine Shedding After 1 or 2 Doses of rVSVΔG-ZEBOV-GP Ebola Vaccine (ERVEBO®): Results From a Phase 2, Randomized, Placebo-controlled Trial in Children and Adults.

BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine (ERVEBO®) is a single-dose, live-attenuated, recombinant vesicular stomatitis virus vaccine indicated for the prevention of Ebola virus disease (EVD) caused by Zaire ebolavirus in individuals 12 months of age and older. METHODS: The Partnership for Research on Ebola VACcination (PREVAC) is a multicenter, phase 2, randomized, double-blind, placebo-controlled trial of 3 vaccine strategies in healthy children (ages 1-17) and adults, with projected 5 years of follow-up (NCT02876328). Using validated assays (GP-ELISA and PRNT), we measured antibody responses after 1-dose rVSVΔG-ZEBOV-GP, 2-dose rVSVΔG-ZEBOV-GP (given on Day 0 and Day 56), or placebo. Furthermore, we quantified vaccine virus shedding in a subset of children's saliva using RT-PCR. RESULTS: In total, 819 children and 783 adults were randomized to receive rVSVΔG-ZEBOV-GP (1 or 2 doses) or placebo. A single dose of rVSVΔG-ZEBOV-GP increased antibody responses by Day 28 that were sustained through Month 12. A second dose of rVSVΔG-ZEBOV-GP given on Day 56 transiently boosted antibody concentrations. In vaccinated children, GP-ELISA titers were superior to placebo and non-inferior to vaccinated adults. Vaccine virus shedding was observed in 31.7% of children, peaking by Day 7, with no shedding observed after Day 28 post-dose 1 or any time post-dose 2. CONCLUSIONS: A single dose of rVSVΔG-ZEBOV-GP induced robust antibody responses in children that was non-inferior to the responses induced in vaccinated adults. Vaccine virus shedding in children was time-limited and only observed after the first dose. Overall, these data support the use of rVSVΔG-ZEBOV-GP for the prevention of EVD in at-risk children. Clinical Trials Registration. The study is registered at ClinicalTrials.gov (NCT02876328), the Pan African Clinical Trials Registry (PACTR201712002760250), and the European Clinical Trials Register (EudraCT number: 2017-001798-18).

Effects of Enrichment Type, Presentation and Social Status on Enrichment Use and Behavior of Sows-Part 2: Free Access Stall Feeding.

Continuing with previous research by our group in an ESF system, four types of enrichment treatments were assessed in gestating sows housed in Free Access Stalls: (1) Constant: constant provision of wood on chain; (2) Rotate: rotation of rope, straw and wood; (3) Stimulus: rotation of enrichments with an acoustic cue; and (4) Control: no enrichment. Treatments had a 12 day-duration. Four groups (28 ± 2 sows) were studied from weeks 6 to 14 of gestation. Groups received all treatments in random order. Three dominant and 3 subordinates per pen were selected using a feed competition test. Digital photos were collected at 10 min intervals for 8 h on days 1, 8, 10 and 12 to record interactions with enrichment. Skin lesions were assessed on days 1 and 12, and salivary cortisol was assessed in weeks 6, 10 and 14 of gestation. More enrichment use was observed in Rotate and Stimulus treatments compared to Constant, and more sows contacted enrichment when straw was provided in the Rotate and Stimulus treatments. There was no difference in the amount of enrichment use by dominants and subordinates, no cortisol concentration elevation in subordinate sows nor any difference in lesion scores. In conclusion, social status had little impact and feeding system is important to reduce stress and aggression.

Safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, administered concomitantly with influenza vaccine in healthy adults aged ≥50 years: a randomized phase 3 trial (PNEU-FLU).

Streptococcus pneumoniae and influenza viruses are associated with significant morbidity and mortality in older adults. Concomitant vaccination against these agents reduces hospitalization and mortality rates. This phase 3 trial evaluated safety, tolerability, and immunogenicity of concomitant and non-concomitant administration of V114, a 15-valent pneumococcal conjugate vaccine containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F, and quadrivalent inactivated influenza vaccine (QIV), in healthy adults aged ≥50 years. Participants (N = 1,200) were randomized 1:1 to receive either V114 administered concomitantly with QIV (concomitant group) or QIV plus placebo (non-concomitant group) on Day 1, followed by placebo (concomitant group) or V114 (non-concomitant group) 30 days later. Randomization was stratified by age and history of pneumococcal polysaccharide vaccine receipt. Overall, 426 (71.0%) and 438 (73.5%) participants in the concomitant and non-concomitant groups experienced solicited injection-site adverse events (AEs); 278 (46.3%) and 300 (50.3%) reported solicited systemic AEs. Most solicited AEs were mild or moderate in severity and of short duration. Non-inferiority for pneumococcal- and influenza-specific antibody responses (lower bound 95% confidence interval of opsonophagocytic activity [OPA] and hemagglutination inhibition geometric mean titers [GMTs] ratios ≥0.5) was demonstrated for concomitant versus non-concomitant administration for all 15 pneumococcal serotypes and all four influenza strains. Consistent with previous studies, a trend was observed toward lower pneumococcal OPA GMTs in the concomitant versus the non-concomitant group. V114 administered concomitantly with QIV is generally well tolerated and immunologically non-inferior to non-concomitant administration, supporting coadministration of both vaccines.

Design of a phase III efficacy, immunogenicity, and safety study of 9-valent human papillomavirus vaccine in prevention of oral persistent infection in men.

BACKGROUND: Seven high-risk human papillomavirus (HPV) types (16/18/31/33/45/52/58) covered by the 9-valent HPV (9vHPV) vaccine cause >90% of HPV-related head and neck cancers (HNCs). An ongoing clinical trial (NCT04199689) was designed to evaluate 9vHPV vaccine efficacy against HPV oral persistent infection, a surrogate endpoint for HPV-related HNCs. METHODS: In this double-blind, placebo-controlled, international trial, men aged 20-45 years (N = 6000) are randomized 1:1 to receive 9vHPV vaccine or placebo on day 1, month 2, and month 6. The primary objective is to demonstrate whether 9vHPV vaccination reduces incidence of HPV16/18/31/33/45/52/58-related 6-month oral persistent infection. Incidence of HPV6/11-related 6-month oral persistent infection will be evaluated as a secondary endpoint. Oral rinse and gargle samples will be collected on day 1, month 7, month 12, and every 6 months thereafter for HPV detection by PCR. Primary analyses will be performed in per-protocol populations. Efficacy in this case-driven study will be analyzed upon accrual of ≥20 primary efficacy endpoint cases. Serum will be collected at day 1 and months 7, 12, 24, 36, and 42; anti-HPV antibody titers will be measured by competitive Luminex immunoassay. Data will be summarized as geometric mean titers and seropositivity rates. Injection-site and systemic adverse events (AEs) will be collected for 15 days post-any vaccination and serious AEs through 6 months after the last vaccination; deaths and vaccine-related serious AEs will be collected throughout the study. DISCUSSION: This trial is expected to generate important data regarding the potential for 9vHPV vaccine to prevent HPV-related head and neck disease.

Effects of Enrichment Type, Presentation and Social Status on Enrichment Use and Behaviour of Sows with Electronic Sow Feeding.

The goal of this study was to identify practical enrichments for sows in partially or fully slatted pen systems. Four treatments were applied: (1) Constant: constant provision of wood on chain; (2) Rotate: rotation of rope, straw and wood enrichments; (3) Stimulus: rotation of enrichments (as in Rotate) with an associative stimulus (bell or whistle); and (4) Control: no enrichment, with each treatment lasting 12 days. Six groups of 20 ± 2 sows were studied from weeks 6 to 14 of gestation in pens with one electronic sow feeder. Each group received all treatments in random order. Six focal animals (3 dominant and 3 subordinate) were selected per pen using a feed competition test. Digital photos were collected at 10 min intervals for 8 h (between 8 a.m. and 4 p.m.) on 4 days/treatment (d 1, 8, 10 and 12) to record interactions with enrichment. Skin lesions were assessed on days 1 and 12, and saliva cortisol samples collected in weeks 6, 10 and 14 of gestation on focal pigs. Sows spent more time in contact with enrichments in Rotate and Stimulus treatments than Constant. Enrichment treatments did not influence lesion scores. Subordinate sows spent more time standing and near enrichments than dominants. Subordinate sows also received more skin lesions and had higher salivary cortisol concentrations than dominants. These results indicate that access to enrichment is valued by sows but can result in greater aggression directed towards subordinates.

Effect of Slat and Gap Width of Slatted Concrete Flooring on Sow Gait Using Kinematics Analysis.

The housing of gestating sows in groups requires sound information about the adapted design of the pen floor. Slatted concrete floors are commonly used for effective drainage of manure but can cause feet injuries and lameness. In the present study, kinematics were used to characterize the gait of 12 gilts and 12 lame sows walking in a corridor on slatted concrete floors with different combinations of slat (85, 105 or 125 mm) and gap (19, 22 or 25 mm) widths. The nine experimental floors were tested with slats in the perpendicular and parallel orientation to the direction of animal walk, according to a duplicated lattice design. Gait parameters were quantified using spatial, temporal and angular kinematics for front and rear limbs. Some parameters were significantly affected by the treatments (p < 0.05), but the effects differed between gilts and lame sows and between slat orientations. Gap width had a significant effect on parameters such as back angle, stride length, foot height, and carpal and tarsal joint angle amplitudes. Slat width significantly affected parameters such as foot height, and carpal and tarsal joint angle amplitudes. Comparisons of the different combinations of slat and gap widths revealed that slats with a width of 105-125 mm and gap width of 19-22 mm had the least effect on the gait characteristics of the gilts and sows.

Season, Transport Duration and Trailer Compartment Effects on Blood Stress Indicators in Pigs: Relationship to Environmental, Behavioral and Other Physiological Factors, and Pork Quality Traits.

The objective of this study was to assess the effects of the season, travel duration and trailer compartment location on blood creatine-kinase (CK), lactate and cortisol concentrations in 384 pigs and assess their relationships with trailer temperature, heart rate and gastrointestinal tract temperature (GTT), behavior, carcass damage scores and meat quality. Blood CK was greater in pigs transported in summer (p = 0.02), after 18 h transportation (p < 0.001) and in pigs located in C4, C5 and C10 (p = 0.002). In winter, the concentration of blood lactate was higher (p = 0.04) in pigs transported for 6 h in C5. Pigs located in C10 showed higher (p = 0.01) concentration of cortisol than those transported for 18h in C4 in summer. The highest correlations were between blood cortisol and GTT (r = 0.53; p < 0.001), and between blood CK and GTT (r = 0.41; p < 0.001), truck temperature (r = 0.42; p < 0.001), and pHu in the longissimus muscle (r = 0.41; p < 0.001). In conclusion, although increased blood cortisol and CK levels appear to indicate a physical stress condition in transported pigs, the weak to moderate correlations with environmental and other animal welfare indicators suggest that blood stress parameters can only be used as a complementary measurement in the assessment of the pigs' response to transport stress.