Search Results (67)

Background/Objectives: Respiratory syncytial virus (RSV) causes a significant hospitalization burden in infants. The objective of this study was to evaluate the cost-effectiveness of introducing clesrovimab, a recently approved long-acting monoclonal antibody, in all US infants born during or entering their first RSV season. Methods: A decision analytical model simulated the clinical and economic impact of clesrovimab in a yearly birth cohort, compared with three alternative interventions: nirsevimab, palivizumab, and the RSVpreF maternal vaccine. Model inputs were obtained from the published literature. Efficacy estimates for clesrovimab were derived from post hoc analyses of randomized control trial data, which were conducted to align endpoints from different studies (nirsevimab and RSVpreF). Medically attended lower respiratory infection (MALRI), quality-adjusted life years (QALYs, 3% discounting), and costs (in 2024 USD) were evaluated from a societal perspective. Both deterministic and probabilistic sensitivity analyses were performed. Results: Clesrovimab resulted in fewer (38,252) RSV-related MALRI outcomes and was cost-saving compared to nirsevimab, with significant reductions in total costs (USD 98 million saved). When compared with palivizumab, clesrovimab and nirsevimab were estimated to cost USD 38,655 and USD 79,912 per QALY, respectively. Results were sensitive to changes in intervention costs, efficacy, and QALY loss due to RSV infection. Conclusions: Clesrovimab may significantly reduce the burden of RSV among US infants in their first RSV season and may save costs compared to nirsevimab. Full article

Background/Objectives: Bordetella bronchiseptica is a Gram-negative bacterium that, either acting alone or in concert with other bacterial or viral pathogens, is a major cause of the canine infectious respiratory disease (CIRD) complex in dogs. Most currently available vaccines are given intranasally or orally and, whilst providing satisfactory reduction in disease severity, can be difficult to use especially in aggressive or anxious dogs. Whilst a small number of injectable B. bronchiseptica vaccines have been developed, little is known about their characteristics with regard to the age at first vaccination, the onset of immunity, duration of immunity, induction of antibody responses, concurrent use with the core vaccines used in most dogs, efficacy in the face of maternally derived antibodies (MDAs) or existing immunity and safety in pregnant animals. Here we describe the development of a safe and efficacious injectable B. bronchiseptica vaccine that utilises a novel process to purify fimbriae. Methods: The fimbrial antigen was formulated with a vitamin E-based oil-in-water adjuvant known to be safe in dogs (Nobivac^® Respira Bb). To evaluate dose response, thirty-nine naïve 5–6-week-old Beagle puppies were allocated to four groups and vaccinated subcutaneously with Nobivac^® Respira Bb at 69 U, 25 U, and 7 U (with a booster at two weeks). All groups were challenged with B. bronchiseptica two weeks after the booster. To evaluate the onset of immunity at 5–6 weeks of age, twenty-one naïve Beagle dogs were split into two groups: group 1 received Nobivac Respira Bb (88 U/dose) plus Nobivac DHPPi and Nobivac L4; group 2 received DHPPi and L4 only. Both groups were challenged with B. bronchiseptica two weeks after the second vaccination. Safety in pregnancy was evaluated by vaccinating pregnant dams and monitoring whelping outcomes and puppy health. Protection in puppies with maternally derived antibodies (MDAs) was studied in 28 pups (11 MDA-negative and 17 MDA-positive from vaccinated and unvaccinated dams). Pups were vaccinated at 5–6 weeks; one group remained unvaccinated to monitor MDA kinetics. All puppies were challenged with B. bronchiseptica at 19 weeks, after MDAs became undetectable. Serology was monitored throughout; daily clinical observations and nasal swabs post-challenge assessed protection and bacterial shedding. Results: Nobivac Respira Bb (MSD Animal Health), was safe for use in 5–6-week-old puppies alongside other Nobivac core canine vaccines without vaccine interference. The vaccine has an onset of immunity of two weeks and significantly reduces both the clinical signs of B. bronchiseptica-induced disease and bacterial excretion into the environment. Furthermore, the vaccine is equally efficacious in puppies with maternally derived antibodies derived from vaccinated dams and can be used safely in pregnant bitches. Conclusions: This vaccine represents a convenient, safe and efficacious alternative to vaccines delivered via the oral or intranasal routes and is a positive addition to the range of vaccines targeted at reducing disease induced by B. bronchiseptica. Full article

The endemicity of H9N2 avian influenza viruses (AIVs), particularly the Y280 lineage, poses persistent challenges to the poultry industry due to the limitations of inactivated vaccines, such as interference by maternally derived antibodies (MDAs) and incomplete suppression of viral replication. This study evaluated the immunogenicity and protective efficacy of a novel recombinant turkey herpesvirus vaccine expressing the hemagglutinin gene of H9N2/Y280 (rHVT-H9/Y280) in commercial Hy-Line Brown layers with high-MDA backgrounds. In a comparative challenge study, the rHVT-H9/Y280 vaccine induced complete protection against a homologous Y280 strain challenge at 4 weeks of age, whereas commercial inactivated vaccines failed to completely block replication, showing virus isolation rates of 16.7–25%. Long-term serological monitoring demonstrated that the rHVT-H9/Y280 vaccine elicited a robust humoral response characterized by persistent maintenance of high HI titers (>8.0 log₂) up to 39 weeks post-vaccination. These findings confirm that rHVT-H9/Y280 effectively overcomes MDA interference and provides protection by inhibition of viral replication in layer chickens, making it a promising candidate for the effective control of H9N2 AIV in endemic regions. Full article

Background: Non-typhoidal Salmonella (NTS) is a major foodborne pathogen, with poultry products, especially eggs, being the primary source of human infections. Current serovar-specific poultry vaccines effectively reduce targeted Salmonella serovars but may inadvertently promote the emergence of untargeted serovars within poultry flocks. Therefore, novel vaccine candidates providing broad cross-serovar protection are needed to improve overall effectiveness of Salmonella control programs. Objectives: This study evaluated the immunogenicity of the novel subunit vaccine candidate InvG and assessed its ability to reduce Salmonella colonization in vaccinated laying hens and their progeny through maternally derived antibodies transferred via egg yolk. Methodology: Three experiments were performed. Experiment I evaluated the immunogenicity of purified recombinant InvG by (a) measuring anti-InvG antibodies using an enzyme-linked immunosorbent assay (ELISA) and (b) completing transcriptomic profiling of immune responses in vaccinated chickens. Vaccinated chickens were subsequently challenged with Salmonella Enteritidis to assess the efficacy of anti InvG antibodies in reducing intestinal colonization of Salmonella. Experiment II involved immunizing hens with InvG, to evaluate passive transfer of antibodies via egg yolk and the protective efficacy of maternally derived antibodies against Salmonella challenge. Passive transfer was assessed by measuring IgY antibodies in hen serum, egg yolk, and progeny serum, as well as secretory IgA (sIgA) antibodies in progeny intestinal washings using ELISA. Protective efficacy was evaluated by orally challenging one-day-old chicks with three different Salmonella serovars. Experiment III assessed the persistence of anti-InvG antibodies in the serum of vaccinated hens and their transfer into eggs following two doses of InvG. Results: InvG vaccination induced robust IgY antibody responses in hens, with efficient maternal antibody transfer to progeny via egg yolk. A statistically significant reduction in Salmonella colonization was observed in both vaccinated hens and their progeny. Conclusions: These findings demonstrate that InvG represents a promising subunit vaccine candidate for Salmonella control in poultry and warrants further investigation towards development as a broadly protective commercial poultry vaccine against Salmonella. Full article

During their early life, puppies are protected against infectious agents with the presence of maternal derived antibodies (MDA). Vaccination is recommended to start as soon as the levels of MDA begin to wane to ensure that the puppy’s immune system can respond effectively to the vaccines and develop active immunity against diseases. Two studies were designed to assess the efficacy of the Canigen^TM DHPPi vaccine in puppies from 6 weeks of age. The studies comprised two parts: the efficacy assessment of the Canine Parainfluenza Virus (CPiV) vaccine component against a virulent challenge with CPiV (Experiment A) and an immunogenicity assessment of Canine Distemper Virus (CDV), Canine Adenovirus (CAV-2), and Canine Parvovirus (CPV-2) vaccine components (Experiment B). In Experiment A, twelve puppies were immunized with two injections of Canigen^TM DHPPi (at minimum titer) two weeks apart and twelve control puppies received the vaccine diluent. All animals were challenged with a virulent, heterologous CPiV strain two weeks after the second vaccination. Vaccinated puppies exhibited a significant reduction in nasal viral shedding compared to the control group. Clinical signs of respiratory disease were mild and transient in both groups. In Experiment B, six puppies were immunized with two injections of Canigen^TM DHPPi (at minimum titer) two weeks apart. A follow-up of the seroneutralizing antibodies titers against the CDV, CAV-2 and CPV-2 vaccine components was performed in order to assess the efficacy on the serological response basis. After the first vaccine injection, all the puppies seroconverted and presented seroneutralizing antibody titers reaching a protective thresholds against CDV (≥10^0.82), CAV-2 and CAV-1 (≥10^0.82), CPV-2 and CPV-2c (≥10^1.8). After the second vaccine injection, a more robust immune response was observed and the seroneutralizing antibody titers remained high until 4 weeks post vaccination for those three vaccine components. In both experiments (A and B), all vaccinated animals remained in good health, with no adverse reactions recorded during the vaccination phase. As a conclusion, the efficacy of the Canigen^TM DHPPi vaccine was demonstrated when administered in dogs from 6 weeks of age. These results fully support the interest of an early vaccination in such young puppies followed by the recommended vaccination scheme. Full article

Antimicrobial resistance (AMR) is an increasing concern in food animal production. In swine herds, viral infections often lead to secondary bacterial disease and higher antimicrobial use (AMU). This study describes how U.S. swine veterinarians view the role of viral vaccines in reducing this reliance on antimicrobials. We conducted a national survey of swine practitioners and follow-up semi-structured interviews with a subset of respondents. Across participants, porcine reproductive and respiratory syndrome (PRRS), swine influenza (SIV), and rotaviral enteritis were most often named as viral diseases in urgent need of improved vaccines. These diseases cause substantial economic losses and frequently trigger AMU in commercial herds. Veterinarians reported several recurring challenges with current vaccines, including limited cross-protection against field strains, interference from maternally derived antibodies, and short duration of protection. Despite these limitations, most respondents supported vaccination as a key tool to curb AMU and indicated they would accept higher prices for clearly improved products. These findings reveal both a clear need and specific opportunities for future vaccine development to provide broader and more reliable protection, reduce AMU, and help slow the development of AMR. Full article

Kittens are born with some maternally derived antibodies (MDA) that, together with maternal gut microbiota, bring some form of early defense against pathogens. However, this protection declines and the rapid changes and challenges the kitten typically encounters can adversely affect their health. Nutrition can modulate the immune system and gut microbiota, offering a boost to protection following weaning. This controlled, randomized, double-blinded study tests a dietary supplement containing nucleotides, oligosaccharides, vitamin E and β-carotene in 50 domestic short-haired kittens. Control kittens were fed standard, dry kitten diet whilst test kittens received the same diet with supplement for 52 weeks. Kittens received routine vaccinations and blood samples were collected throughout the study for standard hematology, serum antibodies and cytokine expression. Rectal fecal samples were analyzed for gut microbiota via 16S rRNA gene sequencing. Supplemented kittens showed significantly improved antibody response to Chlamydia vaccine at various timepoints versus controls, with no consistent effects of supplementation on responses to other vaccines. Several cytokines were significantly influenced by the supplement, which also significantly altered gut microbiota diversity. In conclusion, a dietary supplement was shown to promote immune response and gut microbiota changes in kittens and may help to support a healthy transition into adulthood. Full article

Preeclampsia (PE) is a serious gestational complication that affects the lives of the mother and the child. Women with PE showed higher levels of pro-inflammatory cytokines secreted by leukocytes compared with women with normal pregnancies. The differences are most noticeable in the percentage of CD16+ monocytes, although the mechanism underlying this increase remains unclear. The CD16 receptor is critical for antibody-dependent cellular cytotoxicity, and by binding to antibodies on the surface of target cells, it activates their death. In this study, we examined the effect of soluble placental factors on the expression of CD16 monocytes and the potential role the soluble form of human leukocyte antigen (HLA) has on CD16 monocyte expression. At the first stage of our study, we collected samples of placental villi fragments from 58 pregnant women (38 women with PE and 20 with a healthy pregnancy). Then we studied the effect of placental villus-conditioned culture medium on CD16 expression by monocytes derived from the same women. It was shown that the content of CD16+ monocytes increased significantly in women with PE within 3 h and to a lesser extent in women with a healthy pregnancy (p = 0.009). Also, the addition of the recombinant histocompatibility HLA-B to the placental villus-conditioned culture medium blocks the induction of CD16 expression on monocytes. At the second stage of our study, we typed HLA class I and class II alleles in the umbilical cord blood samples and the venous blood samples taken from 38 women with PE and 40 women with a normal pregnancy. It was found that certain HLA class II alleles predominate in women with preeclampsia. The DRB1*01:01:01G allele showed the greatest difference (p < 0.001). Analyzing five alleles simultaneously makes it possible to predict the PE with AUC = 0.76. Evaluation of unique children’s alleles also showed that class II alleles have greater differences among them than class I alleles. The DQB1*06:03:01G allele had the greatest differences with p = 0.03 (the number was higher in the control group). Performing an analysis of four alleles of children simultaneously allowed us to predict PE with an AUC of 0.64. This work suggests that the activation of CD16+ monocyte expression occurs due to the interaction of soluble placental antigens with monocytes. The most likely way to activate CD16 expression on monocytes is by HLA class II (both maternal and fetal) interaction with CD4 receptors on the surface of monocytes, whereas HLA class I is capable of blocking this process. Evaluation of maternal HLA alleles may be a significant marker for predicting PE. Full article

Background/Objectives: Maternally derived antibody (MDA) levels of porcine circovirus 2 (PCV2) may eventually interfere with humoral response and vaccination efficacy. This study aimed to evaluate the efficacy of a ready-to-use PCV2d and Mycoplasma hyopneumoniae combined vaccine in piglets with different PCV2 MDA levels at vaccination in an experimental inoculation with a heterologous viral genotype. Methods: Forty-eight piglets were allocated into vaccinated (V) and non-vaccinated (NV) groups with high (H) and low (L) PCV2 MDA subgroups (H-V, H-NV, L-V, L-NV). At 3 weeks of age, the piglets received either one dose of vaccine or placebo. Five weeks later, all animals were intranasally challenged with a PCV2b inoculum. Body weight was registered at different time points. Blood samples, peripheral blood mononuclear cells and tracheobronchial lymph nodes (TBLN) were collected and used to assess viraemia, viral load, humoral and cellular responses and histological lesions. Results: The V group showed higher PCV2 antibody levels from challenge onwards, along with a lower percentage of viraemic pigs and reduced viral load in serum at 2 and 3 weeks post-challenge (wpc) and in TBLN tissues compared to the NV group. The H-V group had the highest antibody levels post-challenge, showed no detectable viraemia and had a lower overall amount of virus in tissues. The NV group (especially H-NV) exhibited increased levels of IFN-γ, IFN-α and TNF-α post-challenge. Conclusions: The tested vaccine elicited humoral and cellular immune responses and reduced viral presence in serum and tissues, demonstrating efficacy in a PCV2 subclinical infection model despite high MDA levels at the time of vaccination. Understanding both humoral and cellular immune responses according to different MDA levels can help design more effective vaccination strategies against PCV2. Full article

Antibody titer testing can be useful in controlling successful puppy immunization and can reduce unnecessary vaccinations in adult dogs. We evaluated three commercially available point-of-care tests (POCTs) for detecting antibodies against canine parvovirus (CPV-2), canine distemper virus (CDV) and canine adenovirus (CAV-1 and/or -2), comparing them to the reference virus neutralization (VN) assay. Sera from 200 client-owned dogs (13 healthy, 63 chronically diseased, 124 acute) and 60 specific pathogen-free (SPF) dogs, including 20 sera with maternally derived antibodies (MDA), were tested. All three POCTs demonstrated high sensitivity (79.0–100%) and specificity (97.8–100%) for CPV-2. In contrast, specificity for CDV and CAV was lower with POCT-1 (43.5% and 55.3%) and POCT-2 (42.4% and 79.2%), despite high sensitivity (CDV in both POCTs 98.7%; CAV POCT-1: 99.4%, POCT-2: 90.8%). POCT-3, by comparison, showed high specificity (CDV: 94.1%; CAV: 84.4%) but very low sensitivity (CDV: 17.4%; CAV: 33.1%). Only POCT-1 for CPV-2 detected MDA reliably, whereas the other two POCTs, and POCT-1 for CDV and CAV, did not. When compared to VN, the agreement in vaccination recommendations was 82% for POCT-1 and POCT-2, and 62% for POCT-3. In conclusion, all three POCTs reliably detected antibodies against CPV-2, including MDA with POCT-1. However, the lower specificity for CDV and CAV antibody detection in POCT-1 and POCT-2 raises concerns about misclassifying unprotected dogs as immune, while false-negatives with POCT-3 could lead to unnecessary vaccinations. Further optimization of all three POCTs for CDV and CAV is recommended. Full article

Background/Objectives: Typically, studies aiming to assess the ability of canine parvovirus (CPV) vaccines to immunise puppies with maternally derived antibody (MDA) are undertaken using group-housed puppies. Since live attenuated vaccine virus is invariably shed in the faeces, this can result in repeated oral re-exposure and puppies which failed to respond to the initial vaccination may respond instead to shed vaccine virus in the environment, thus artificially enhancing the efficacy of the vaccine. This problem can be avoided by adopting a pair-housed study design where one vaccinated pup is housed with one unvaccinated sentinel. Using this design, we examine the capability of four commercially available canine parvovirus vaccines to immunise MDA-positive pups. Methods: Thirty-four 6-week-old puppies born to vaccinated dams were divided into four vaccine groups with similar MDA ranges. Within each group puppies were paired based on matching MDA titres, and each pair was housed in separate biocontainment accommodation. In each pair, the pup with the highest MDA was vaccinated and the other left as an unvaccinated sentinel. All vaccinates were given a single dose of one of the vaccines. Vaccinates and sentinels were then bled every 2–4 days and CPV antibody was measured. Daily rectal swabs were also collected from all pups to identify any shed vaccinal CPV. Results: All the pups vaccinated with Nobivac DP PLUS seroconverted, with significantly higher antibody titres compared to the pups in other vaccine groups, all shed vaccine virus, and all bar one of the sentinel pups seroconverted. In the other groups, only vaccinated pups with lower levels of MDA seroconverted and shed vaccine virus but none of the sentinel pups seroconverted. Conclusions: Different canine parvovirus vaccines differ in their ability to replicate in and immunise puppies with MDA, the levels of which may vary widely between individuals. The shedding of vaccinal CPV is an important consideration when designing studies to demonstrate efficacy in MDA-positive puppies. Full article

Background/Objectives: More than 33 billion chickens are industrially raised for meat and egg production globally and vaccinated against Marek’s disease virus (MDV). The antigenically related herpesvirus of turkey (HVT) is used as a live-attenuated vaccine, commonly provided as a recombinant vector to protect chickens against additional unrelated pathogens. Because HVT replicates in a strictly cell-associated fashion to low levels of infectious units, adherent primary chicken or duck embryo fibroblasts are infected, dislodged from the cultivation surface and distributed as cryocultures in liquid nitrogen to the site of application. Although viable cells are complex products, application of infected cells in ovo confers protection even in presence of maternal antibodies. Methods/Results: The aim of our study was to determine whether a continuous cell line in a scalable cultivation format can be used for production of HVT-based vaccines. The AGE1.CR cell line (from Muscovy duck) was found to be highly permissive in adherent cultures. Propagation in suspension, however, initially gave very low yields. The induction of cell-to-cell contacts in carrier-independent suspensions and a metabolic shock improved titers to levels suitable for vaccine production (>10⁵ infectious units/mL after infection with multiplicity of 0.001). Conclusions: Production of HVT is challenging to scale to large volumes and the reliance on embryonated eggs from biosecure facilities is complex. We demonstrate that a cell-associated HVT vector can be propagated in a carrier-independent suspension culture of AGE1.CR cells in chemically defined medium. The fed-batch production is independent of primary cells and animal-derived material and can be scaled to large volumes. Full article

Background/Objectives: This study aimed to determine the changes in BVDV (bovine viral diarrhea virus), BoHV-1 (bovine herpesvirus-1), and BRSV (bovine respiratory syncytial virus) antibody levels until weaning in calves who ingested colostrum from vaccinated dairy cattle. Additionally, it aimed to measure the antibody levels induced by the vaccine administered before and after socialization after weaning. Methods: Exposure to respiratory viral and bacterial agents was monitored by PCR analysis using nasal swabs at regular intervals from birth to weaning (pre-colostral and after the 2nd, 7th, 15th, 25th, 35th, 45th, 55th, and 65th days). The levels of colostral BVDV, BoHV-1, and BRSV antibodies were monitored using an enzyme-linked immunosorbent assay (ELISA) at the same intervals from birth to weaning (pre-colostral and after the 2nd, 7th, 15th, 25th, 35th, 45th, 55th, and 65th days). Results: The highest level of maternal antibodies in the blood was detected on day 7. BoHV-1, BVDV, and BRSV antibody levels decreased steadily until weaning by 69.14%, 38%, and 53%, respectively. Conclusions: Vaccination strategies should be planned by considering the presence of maternally derived antibodies and minimizing stress that may negatively affect vaccine titers, thus maximizing vaccine efficacy in calves. Full article

Background and Objectives: Canakinumab, a human recombinant monoclonal antibody against interleukin-1ß (IL-1ß), is indicated for the treatment of selected autoinflammatory periodic fever syndromes and rheumatic diseases. Data on its use during pregnancy remain limited and all are primarily derived from case reports. Although animal studies indicate no evidence of reproductive toxicity, the risk to the fetus or mother remains unknown. This study aims to provide more findings about this important topic. Methods: A retrospective analysis was conducted on three patients followed and treated in the National Center for Periodic Fever Syndromes. Although due to the small sample size, no general conclusions regarding the safety of canakinumab during pregnancy can be drawn. Results: Three maternal-exposed pregnancies were assessed, with no paternal exposure. Diagnoses included mevalonate kinase deficiency, familiar Mediterranean fever and TNF-receptor-associated periodic syndrome. All mothers were treated with canakinumab, and two of those continued the canakinumab treatment during the whole course of pregnancy. The diseases remained under full control during pregnancy, enabling conception in two cases where attempts prior to treatment were unsuccessful. The therapy led to disease control, a reduction in inflammation and subsequently successful conception. One patient underwent IVF repeatedly. All pregnancies resulted in three healthy infants, with no reported miscarriages during the canakinumab-exposed pregnancies, no complications during pregnancies and no serious infections in the newborns. The children had normal development, without any developmental delays or chronic illnesses. Conclusions: The current data, including our findings, indicate no harmful effects of canakinumab during pregnancy. However, because of the scarcity of data, the use of canakinumab during pregnancy should be carefully managed, and women who want to become pregnant should continue treatment only after a thorough benefit–risk evaluation. Full article

Background: Maternal-derived antibody (MDA) interferes with immune responses, leading to the failure of H9N2 avian influenza vaccinations in poultry. So far, none of the commercially available H9N2 avian influenza vaccines used in poultry have been able to overcome MDA interference. Methods: To develop a vaccine that can overcome MDA interference, one or multiple copies of the minimum-binding domain (P29) from the complement protein C3d were inserted in between the signal peptide and the head domain of the hemagglutinin (HA) protein on a H9N2 avian influenza virus (A/Chicken/Shanghai/H514/2017, named H514). Results: The HA proteins containing P29 stimulated stronger type I interferences than wild-type HA proteins in vitro. The modified viruses with the HA proteins containing one copy of P29 (rH514-P29.1) and two copies of P29.2 (rH514-P29.2) were successfully rescued using reverse genetics. The inactivated vaccines developed with rH514-P29.1 or rH514-P29.2 induced higher and faster humoral immune responses than the vaccine developed with rH514 in specific pathogen-free (SPF) chickens. To evaluate the vaccines’ efficacy in the presence of MDA and to ensure a uniform level of MDA, passively transferred antibody (PTA) was used as a model to mimic MDA in 1-day-old SPF chickens. Our results showed that the rH514-P29.2 inactivated vaccine induced significantly higher HI titers than the rH514 inactivated vaccine in the presence of PTA. More importantly, it reduced viral shedding after being challenged with H514 in the presence of PTA. Conclusions: Our results suggest that vaccine antigens fused with two copies of P29 can decrease the interference of MDA on immunity in chickens. Overall, our results provide a new strategy for overcoming MDA interference. Full article