Passive Immunization Research Articles

Assessment of the immunity gap of two vaccination programs against Gumboro disease in Luong Phuong chicken

Maternal-derived antibody (MDA) is the priority protection against environmental Infectious Bursal Disease Virus (IBDV) in the first weeks. The passive immunity decreases, but the active immunity is not enough to protect chicks, so shortening the high-risk period is crucial to IBD control. The objective of this study was to evaluate the immunity gap between 2 vaccination programs against infectious bursal disease (IBD) in Luong Phuong chickens. A total of 34,600 chicks were administered by subcutaneous injection of IBD vaccine at 0.1 mL/dose at the hatchery. At 12 days old, 18,000 chicks were vaccinated with the M.B strain vaccine and 16,600 chicks were vaccinated with the 228E strain vaccine by drinking water. The IBD and Newcastle disease (ND) antibody evaluations were based on the Enzyme-linked immunosorbent assay (ELISA) technique. Parameters were recorded until slaughter including body weight, average daily gain, feed conversion rate, and mortality. The IBD MDA at 1 day old was medium and uniform (3809 and 45.3%), which could protect against IBD virus from 1 to 2 weeks old. At 28 days old, the IBD antibody titer of the MB vaccine was higher than that of the 228E vaccine, various proportions of samples in the M.B group exceeding 1,000 titers (40% vs. 0%), and it was a statistically significant difference (1,133 vs. 161) (P < 0.01). Besides, the M.B vaccine created a faster and stronger immune response than the 228E vaccine, shortening the immune gap and protecting chicks earlier. The humoral immune response to the ND vaccine was good, with no difference between 2 groups, which proved that the M.B virus did not cause immunosuppression. The production parameters of chickens between the 2 groups were the same. In summary, the M.B vaccine made a short immune gap and did not cause immunodeficiency in chickens.

Quantifying the impact of frequent diseases and syndromes on calf health using the opinions of producers and veterinarians: Towards dairy calf disability weights.

The first objective of this study was to quantify the impact and disability weight (DW) of frequent diseases or syndromes of pre-weaned dairy calves using the perceptions of producers and veterinarians. The second objective was to compare the opinions of producers and veterinarians regarding the impact and DW of dairy calves' frequent diseases and syndromes. A survey was conducted to obtain demographic information and opinions of 39 dairy producers and 52 veterinarians on the impact of frequent disease and syndromes on calf health. Most of the producers (97.4%, 38/39) were clients of the ambulatory clinic at the Faculté de médecine vétérinaire de l'Université de Montréal (FMV, UdeM) in Saint-Hyacinthe, Québec, Canada. They were actively engaged in calf research projects. Québec veterinarians were contacted via email through their association. Additionally, veterinarians from the bovine ambulatory clinic and the bovine veterinary hospital at the FMV, UdeM, were contacted directly via email. A visual analog scale, represented by a horizontal line ranging from 0 (no impact) to 10 (maximum impact (i.e., death or euthanasia)), was used to estimate the impact of 9 frequent diseases or syndromes (diarrhea, dystocia, inadequate transfer of passive immunity, fracture, wound or abscess, arthritis, respiratory disease, umbilical infection, and congenital defect) on calf health following previously reported methods (using the most probable, and range of the perceived impact for each participant and disease). The DW values were obtained by converting the impact values to a probability density in a scale from 0 to 1 using betaPERT method. Average impacts and DW were quantified for each frequent disease and syndrome. Average impact differed statistically across different diseases and syndromes. The highest average impacts were obtained for the presence of a fracture (6.49/10), arthritis (6.22/10), and congenital defects (6.03/10), while the lowest impact was observed for the presence of a wound or abscess (3.42/10). The opinions of producers and veterinarians were similar for most of the selected diseases and syndromes; however, statistical differences were observed for arthritis (producers = 5.13 vs veterinarians = 6.88), umbilical infection (producers = 3.65 vs veterinarians = 4.74), and dystocia (producers = 3.87 vs veterinarians = 4.58). A strong correlation coefficient (0.72) was observed between the observed ranks of diseases and syndromes of producers and veterinarians. In conclusion, we quantified how frequent diseases and syndromes affect calf health. Producers and veterinarians mostly agreed on their impact. Estimating DW is a crucial first step in creating a health measure for dairy calves. Similar to humans, this metric will be important for health comparative analysis for producers, veterinarians, and industry.

Developing a human monoclonal antibody combination CRM25 to prevent rabies after exposure

Immunization against rabies post-exposure prophylaxis (PEP) requires passive immunization with either monoclonal antibody (mAb) or blood-derived rabies immunoglobin (RIG). Currently, replacing traditional RIG with emerging mAb or mAb combinations is highly recommended due to the limited supply and potential safety risks of RIG. Here, we developed a mAb combination named CRM25 by combining two human mAbs, RM02 and RM05, at a 1:1 mass ratio. RM02 and RM05 were non-competing and non-overlapping mAbs targeting epitopes I and III, respectively. K226 and G229 were found to be the critical amino acid sites for RM02 neutralization, but the mutant I338T displayed decreased susceptibility to RM05 neutralization. Notably, CRM25 was capable of cross-neutralizing rabies virus (RABV) strains containing K226M or I338T mutations. CRM25 additionally showed an inhibitory effect on the infection of all tested common RABVs and non-RABV phylogroup I lyssaviruses. CRM25 not only exhibited neutralizing activity but also exhibited antiviral effects via Fc-mediated effector functions. Importantly, CRM25 was comparable to human RIG in terms of its capacity to protect Syrian golden hamsters from lethal RABV challenges. These findings promote more thorough research on CRM25′s antiviral properties in cells and in vivo to enhance its clinical applicability and suggest that it may be a viable candidate medication for rabies PEP.

Respiratory syncytial virus (RSV) prevention: Perception and willingness of expectant parents in the Netherlands

BackgroundRespiratory syncytial virus (RSV) is a leading cause of infant respiratory disease. Recent approval of preventive measures like a long-acting monoclonal antibody and a maternal vaccine signals a potential shift in early-life RSV infection control. However, success hinges on acceptance. MethodsWe conducted a cross-sectional survey among pregnant women and partners in the Netherlands, recruited via healthcare professionals, social media platforms, and the 9-Months Fair. The survey assessed willingness and motivation for maternal RSV vaccination and neonatal RSV immunization, including strategy preferences and informational needs. ResultsIn total 1001 pregnant women (mean age: 31.1 years) and their partners (mean age: 33.2 years) completed the survey. On average, they were 24 weeks pregnant at the time, and 54.6 % had no other children yet. The majority was Dutch-born (95.2 % of women); with 68.3 % of women having completed higher education and with overall strong pro-vaccination attitudes (93.9 % of partners intended to vaccinate their expected newborn). The overall acceptability to vaccination and immunization was high, with 87 % of respondents indicating they would (likely) accept both strategies. A positive attitude towards both methods was associated with previous experience with severity of RSV, intention to vaccinate the newborn and parental vaccination status during childhood and current pregnancy. When the choice was given, the majority of participants, in particular those with children and the intention to breastfeed, favoured maternal vaccination over passive immunization of infants (75.3 % of the pregnant and 71.6 % of the partners). A majority of the respondents cited optimal protection for the child and knowledge of RSV as important factors for accepting RSV prophylaxis. ConclusionsWhile most participants would accept both strategies for RSV protection of their infant, a majority, especially those with other children, favoured maternal vaccination, due to concerns about infant safety and awareness of RSV severity.

Respiratory Syncytial Virus: A WAidid Consensus Document on New Preventive Options

Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections, particularly affecting young infants, older adults, and individuals with comorbidities. Methods: This document, developed as a consensus by an international group of experts affiliated with the World Association of Infectious Diseases and Immunological Disorders (WAidid), focuses on recent advancements in RSV prevention, highlighting the introduction of monoclonal antibodies (mAbs) and vaccines. Results: Historically, RSV treatment options were limited to supportive care and the monoclonal antibody palivizumab, which required multiple doses. Recent innovations have led to the development of long-acting mAbs, such as nirsevimab, which provide season-long protection with a single dose. Nirsevimab has shown high efficacy in preventing severe RSV-related lower respiratory tract infections (LRTIs) in infants, reducing hospitalizations and ICU admissions. Additionally, new vaccines, such as RSVpreF and RSVpreF3, target older adults and have demonstrated significant efficacy in preventing LRTIs in clinical trials. Maternal vaccination strategies also show promise in providing passive immunity to newborns, protecting them during the most vulnerable early months of life. This document further discusses the global burden of RSV, its economic impact, and the challenges of implementing these preventative strategies in different healthcare settings. Conclusions: The evidence supports the integration of both passive (mAbs) and active (vaccines) immunization approaches as effective tools to mitigate the public health impact of RSV. The combined use of these interventions could substantially reduce RSV-related morbidity and mortality across various age groups and populations, emphasizing the importance of widespread immunization efforts.

New Development of Vaccine Technology in Tumor Therapy

Abstract. Cancer vaccines are a crucial component of tumors immunotherapy, offering the advantage of minimizing adverse reactions to induce tumor regression. They also enable the establishment of lasting anti-tumor memory. Recent years have seen significant breakthroughs in cancer vaccines, including the customization of personalized vaccines and the transition from passive immunization to active treatment. Currently, most cancer vaccine future goals focus on improving cost and efficiency such as combining immunology and bioinformatics to predict more accurate vaccine epitopes. This paper focuses on three innovative technologies in therapeutic cancer vaccines: cell vaccine, peptide cancer vaccine and nucleic acid cancer vaccine. This paper summarizes new selection of antigen-presenting cells for autologous tumor cell vaccine and allogeneic tumor cell vaccine, new research on adjuvants of peptide cancer vaccines and new nucleic acid cancer vaccine delivery platform. In addition, the combination of therapeutic vaccines is briefly discussed. These new technologies offer cancer patients new treatment options and hope.

A Passion for Small Things and Staying Primed: My Career in Virology and Immunology.

A love of science and animals, perseverance, and happenstance propelled my career in veterinary virology and immunology. I have focused on deadly enteric and respiratory viral infections in neonatal livestock and humans with an aim to understand their prevalence, pathogenesis, interspecies transmission, and immunity and develop vaccines. Research on animal coronaviruses (CoVs), including their broad interspecies transmission, provided a foundation to understand emerging zoonotic fatal human respiratory CoVs [severe acute respiratory syndrome, Middle East respiratory syndrome, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)] and reverse zoonosis of SARS-CoV-2 to animals. A highlight of my early research was the discovery of the gut-mammary gland-sIgA axis, documenting a common mucosal immune system. The latter remains pivotal to designing maternal vaccines for passive immunity in neonates. Our discovery and innovative cell propagation of fastidious human and animal rotaviruses and caliciviruses and their infectivity in germ-free animals has provided cell-adapted and animal disease models for ongoing virologic and immunologic investigations and vaccines. Nevertheless, besides the research discoveries, my lasting legacy remains the outstanding mentees who have enriched my science and my life.

Retraction: Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease.

Retraction: Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease.

A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions.

To eliminate vertical HIV transmission and achieve therapy-free viral suppression among children living with HIV, novel strategies beyond antiretroviral therapy (ART) are necessary. Our group previously identified a triple broadly neutralizing antibody (bNAb) combination comprising of 3BNC117, PGDM1400 and PGT151 that mediates robust in vitro neutralization and non-neutralizing effector functions against a cross-clade panel of simian human immunodeficiency viruses (SHIVs). In this study, we evaluated the safety, pharmacokinetics, and antiviral potency of this bNAb combination in infant rhesus macaques (RMs). We demonstrate that subcutaneous infusion of the triple bNAb regimen was well tolerated in pediatric monkeys and resulted in durable systemic and mucosal distribution. Plasma obtained from passively-immunized RMs demonstrated potent HIV-neutralizing and Fc-mediated antiviral effector functions. Finally, using the predicted serum neutralization 80% inhibitory dilution titer (PT80) biomarker threshold of >200, which was recently identified as a surrogate endpoint for evaluation of the preventative efficacy of bNAbs against mucosal viral acquisition in human clinical trials, we demonstrated that our regimen has PT80>200 against a large panel of plasma and breast milk-derived HIV strains and cross-clade SHIV variants. This data will guide the development of combination bNAbs for eliminating vertical HIV transmission and for achieving ART-free viral suppression among children living with HIV.

Novel Approaches to Allergen Immunotherapy for Respiratory Allergies.

Allergen immunotherapy (AIT) remains the cornerstone for managing respiratory allergies, offering long-term symptom relief, disease modification, and prevention of disease progression. While novel approaches like intralymphatic and epicutaneous immunotherapy and the combination of allergens with adjuvants show promise, traditional methods remain effective and safe. Hypoallergenic T-cell peptide vaccines and recombinant allergens require further research to confirm their clinical benefits. Passive immunotherapy, while demonstrating effectiveness in specific cases, needs exploration of its long-term efficacy and broader applicability. Combining AIT with biologics may enhance safety and treatment outcomes. Despite emerging innovations, allergen-specific immunotherapy with natural allergen extracts remains the primary disease-modifying treatment, offering long-term symptom relief and prevention of disease progression. Continued research is essential to refine and optimize allergen immunotherapy strategies, providing patients with more effective and personalized treatment options.

Landscape of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirusgenus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.

Monoclonal antibodies against the spike protein alter the endogenous humoral response to SARS-CoV-2 vaccination and infection.

Increased use of antiviral monoclonal antibodies (mAbs) for treatment and prophylaxis necessitates better understanding of their impact on endogenous immunity to vaccines and viruses. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presented an opportunity to study immunity in individuals who received antiviral mAbs and were subsequently immunized with vaccines encoding the mAb-targeted viral spike antigen. Here, we describe the impact of administration of an antibody combination, casirivimab plus imdevimab (CAS+IMD), on immune responses to subsequent SARS-CoV-2 vaccination in humans, nonhuman primates, and mice. The presence of CAS+IMD at the time of vaccination led to a specific diminishment of vaccine-elicited pseudovirus neutralizing antibody titers without overall dampening of spike protein-directed immune responses, including antibody, B cell, and T cell responses. The impact on pseudovirus neutralizing titers extended to other therapeutic anti-spike protein antibodies when used as either monotherapy or combination therapy. The specific reduction in pseudovirus neutralizing titers was the result of epitope masking, a phenomenon where specific epitopes are bound by high-affinity antibodies and blocked from B cell recognition. Encouragingly, this reduction in pseudovirus neutralizing titers was reversible with additional booster vaccination. Moreover, by assessing the antiviral immune response in SARS-CoV-2-infected individuals treated therapeutically with CAS+IMD, we demonstrated alteration of antiviral humoral immunity in those who had received mAb therapy, but only in those individuals who had yet to start mounting their natural immune response at the time of mAb treatment. Together, these data demonstrate that antiviral mAbs can alter endogenous humoral immunity during vaccination or infection.

Linking Antibodies Against Apolipoprotein A-1 to Metabolic Dysfunction-Associated Steatohepatitis in Mice.

Metabolic dysfunction-associated fatty liver disease (MASLD) is a common liver and health issue associated with heightened cardiovascular disease (CVD) risk, with Cytokeratin 18 (CK-18) as a marker of liver injury across the MASLD to cirrhosis spectrum. Autoantibodies against apolipoprotein A-1 (AAA-1s) predict increased CVD risk, promoting atherosclerosis and liver steatosis in apoE-/- mice, though their impact on liver inflammation and fibrosis remains unclear. This study examined AAA-1s' impact on low-grade inflammation, liver steatosis, and fibrosis using a MASLD mouse model exposed to AAA-1s passive immunization (PI). Ten-week-old male C57BL/6J mice under a high-fat diet underwent PI with AAA-1s or control antibodies for ten days. Compared to controls, AAA-1-immunized mice showed higher plasma CK-18 (5.3 vs. 2.1 pg/mL, p = 0.031), IL-6 (13 vs. 6.9 pg/mL, p = 0.035), IL-10 (27.3 vs. 9.8 pg/mL, p = 0.007), TNF-α (32.1 vs. 24.2 pg/mL, p = 0.032), and liver steatosis (93.4% vs. 73.8%, p = 0.007). Transcriptomic analyses revealed hepatic upregulation of pro-fibrotic mRNAs in AAA-1-recipient mice, though histological changes were absent. In conclusion, short-term AAA-1 PI exacerbated liver steatosis, inflammation, and pro-fibrotic gene expression, suggesting that AAA-1s may play a role in MASLD progression. Further research with prolonged AAA-1 exposure is warranted to clarify their potential role in liver fibrosis and associated complications.

Macromineral, micromineral and metal concentration of bovine colostrum samples from Salzburg, Austria

BackgroundBesides immunoglobulins which are essential for the calf to prevent Failure of Transfer of Passive Immunity (FTPI) colostrum contains multiple other constituents such microminerals, macrominerals and metals. The concentration of the minerals seems to be higher in colostrum than in normal milk. The aims of this study were to describe macromineral, micromineral and metal concentration of bovine colostrum samples from Salzburg, Austria and to see if there are differences in the concentrations between different cow feeding strategies and farm locations. MethodsTherefore, 1050 individual colostrum samples were collected from 72 dairy farms from different districts of Salzburg. All colostrum samples were analysed for macromineral (K, Mg, Na), micromineral (Co, Cu, Fe, I, Mg, Se, Zn) andmetal (As, Ba, Cd, Li, Mo, Ni, Pb, Sr, Tl, U) concentrations by inductive coupled plasma mass spectrometry. ResultsThe mean K, Mg and Na levels were 1218.71 mg l-1, 245.44 mg l-1 and 358.62 mg l-1, respectively. The micromineral concentrations of I, Se, Co and Zn were significantly higher in colostrum from dairy cows feeding a Total-Mixed-Ration during the lactation period in comparison to cows receiving microminerals by hand feeding, transponder feeding or via a licking bucket or licking stone. The metal analysis showed that in three farms, most of the colostrum samples showed Pb levels above the limit of 5 µg l-1. ImplicationsHerd-level factors need to be addressed to elevate micromineral concentrations and to reduce metal concentrations in colostrum from dairy cows from Salzburg, Austria. ConclusionThe results show that the macrominerals K, Mg and Na are within the range of published concentrations. For the microminerals, Co, Cu, Fe, I, Mg, Se and Zn the concentrations were significantly different depending on the mineral feeding strategies during the lactation and dry period. Metal concentrations of As, Ba, Cd, Li, Mo, Ni, Pb, Sr, Tl and U differed between the districts of Salzburg.

BK polyomavirus serotype-specific antibody responses in blood donors and kidney transplant recipients with and without new-onset BK polyomavirus-DNAemia: A Swiss Transplant Cohort Study

BK polyomavirus (BKPyV) causes premature renal failure in 10% to 30% of kidney transplant recipients (KTRs). Current guidelines recommend screening for new-onset BKPyV-DNAemia/nephropathy and reducing immunosuppression to regain BKPyV-specific immune control. Because BKPyV encompasses 4 major genotype (gt)-encoded serotypes (st1,-2,-3,-4), st-specific antibodies may inform the risk and course of BKPyV-DNAemia/nephropathy. Using BKPyV st-virus-like particle (VLP) enzyme-linked immunosorbent assay, we analyzed plasma from 399 blood donors (BDs) and 428 KTRs (134 KTR-cases with BKPyV-DNAemia, 294 KTR-controls). BDs were anti-BKPyV-VLP immunoglobulin G–seropositive in 85% compared to 93% of KTRs at the timepoint at transplantation (T0) (P < .001). Anti-st1 was predominant in both groups followed by anti-st4, anti-st2, and anti-st3. Antibody levels and quadruple sero-reactivity at T0 were higher in KTR-controls than in KTR-cases (P = .026) or in BDs (P < .001). In KTR-cases, anti-st increased posttransplant (P < .0001) and independently of ongoing or cleared BKPyV-DNAemia. However, anti-st levels were significantly higher at T0 in KTR-cases able to clear at timepoint 6-month posttransplant or timepoint 12-month posttransplant. In 34 KTR-cases with deep genome sequencing, BKPyV-gtI was predominant, and anti-st1 and st1-neutralizing antibodies were significantly lower at T0 than in KTR-controls. Thus, BKPyV st-specific antibody levels at transplantation might reflect gt/st-BKPyV-specific immunity clearing or preventing BKPyV-DNAemia in KTR-cases or KTR-controls, respectively. Accordingly, active or passive immunization may be the most efficient pretransplant or early posttransplant.

A Synthetic Oligosaccharide Resembling Francisella tularensis Strain 15 O-Antigen Capsular Polysaccharide as a Lead for Tularemia Diagnostics and Therapeutics.

Francisella tularensis, a category A bioterrorism agent, causes tularemia in many animal species. F. tularensis subspecies tularensis (type A) and holarctica (type B) are mainly responsible for human tularemia. The high mortality rate of 30-60 % caused by F. tularensis subspecies tularensis if left untreated and the aerosol dispersal renders this pathogen a dangerous bioagent. While a live attenuated vaccine strain (LVS) of F. tularensis type B does not provide sufficient protection against all forms of tularemia infections, a significant level of protection against F. tularensis has been observed for both passive and active immunization of mice with isolated O-antigen capsular polysaccharide. Well-defined, synthetic oligosaccharides offer an alternative approach towards the development of glycoconjugate vaccines. To identify diagnostics and therapeutics leads against tularemia, a collection of F. tularensis strain 15 O-antigen capsular polysaccharide epitopes were chemically synthesized. Glycan microarrays containing synthetic glycans were used to analyze the sera of tularemia-infected and non-infected animals and revealed the presence of IgG antibodies against the glycans. Two disaccharide (13 and 18), both bearing a unique formamido moiety, were identified as minimal glycan epitopes for antibody binding. These epitopes are the starting point for the development of diagnostics and therapeutics against tularemia.

A Synthetic Oligosaccharide Resembling Francisella tularensis Strain 15 O‐Antigen Capsular Polysaccharide as a Lead for Tularemia Diagnostics and Therapeutics

AbstractFrancisella tularensis, a category A bioterrorism agent, causes tularemia in many animal species. F. tularensis subspecies tularensis (type A) and holarctica (type B) are mainly responsible for human tularemia. The high mortality rate of 30–60 % caused by F. tularensis subspecies tularensis if left untreated and the aerosol dispersal renders this pathogen a dangerous bioagent. While a live attenuated vaccine strain (LVS) of F. tularensis type B does not provide sufficient protection against all forms of tularemia infections, a significant level of protection against F. tularensis has been observed for both passive and active immunization of mice with isolated O‐antigen capsular polysaccharide. Well‐defined, synthetic oligosaccharides offer an alternative approach towards the development of glycoconjugate vaccines. To identify diagnostics and therapeutics leads against tularemia, a collection of F. tularensis strain 15 O‐antigen capsular polysaccharide epitopes were chemically synthesized. Glycan microarrays containing synthetic glycans were used to analyze the sera of tularemia‐infected and non‐infected animals and revealed the presence of IgG antibodies against the glycans. Two disaccharide (13 and 18), both bearing a unique formamido moiety, were identified as minimal glycan epitopes for antibody binding. These epitopes are the starting point for the development of diagnostics and therapeutics against tularemia.

Effect of Blood Sampling Time After Colostrum Intake on the Concentration of Metabolites Indicative of the Passive Immunity Transfer in Newborn Dairy Calves.

Due to the synepitheliochorial placental structure, bovines show no maternal antibody flow from mother to fetus during pregnancy, resulting in an agammaglobulemic newborn [...].

Linking antibody against apolipoprotein A-1 to metabolic dysfunction-associated steatohepatitis in mice

Abstract Background Metabolic dysfunction-associated fatty liver disease (MASLD) is a common liver condition associated with increased cardiovascular disease (CVD) risk. Cytokeratin 18 (CK-18) is indicative of liver injury and used as a surrogate biomarker covering MASLD to cirrhosis phenotypes. Autoantibodies against apolipoprotein A-1 (AAA-1) are known CVD risk factors inducing MASLD in vitro, but their role in modulating steatohepatitis and fibrosis in vivo is still elusive. We investigated AAA-1's contribution to systemic low-grade inflammation, liver steatosis, and fibrosis using a MASLD mouse model and a validated passive immunization protocol (PIP). Methods 10 weeks-old male C57BL/6J mice were fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) and immunized with AAA-1 (200ug) or control antibodies for ten days. At sacrifice, plasma samples were collected, and CK-18 levels, and proinflammatory cytokines were measured using the Mesoscale Discovery platform. Hematoxylin and Eosin and Sirius Red Fast Green staining were used to reveal liver steatosis and fibrosis, respectively. RNA were extracted from mouse liver samples and mRNA were then analyzed using a commercial fibrosis-specific genes panel (nCounter Human Fibrosis V2 Panel) and the nCounter Analysis System. Results Compared to control IgG recipients, CDAHFD mice injected with AAA-1 exhibited significantly elevated plasma levels of CK-18 (5.3 vs 2.1, p=0.031), IL-6 (13 vs 6.9, p=0.035), IL-10 (27.3 vs 9.8, p=0.007) and TNF-α (32.1 vs 24.2, p=0.032), and liver steatosis (93.4% vs 73.8%, p=0.007). Nanostring technology experiments revealed upregulation of several pro-fibrotic m-RNAs in liver tissue from AAA-1 immunized mice compared to the IgG immunized control group. These included Serum Amyloid A (Fold Change (FC) AAA-1 vs IgG : 2.5, p=0.02) , G-protein coupled receptors 65 (FC: 2.7, p=0.01), Periostin (FC: 2.6, p=0.001), Phospholipid transfer protein (FC: 2.2, p=0.0004), Vascular Cell Adhesion Molecule 1 (FC: 2.5, p=0.02) and Angiopoietin-like 4 (FC: 2.8, p=0.01). Histologically, the amount of liver fibrosis remained unaffected, probably due to the short time of the study. Conclusions Short AAA-1 PIP induced enhanced liver steatosis and inflammation accompanied by an elevation of the expression of several pro-fibrotic genes in CDAHFD mice, suggesting that AAA-1 may contribute to the transition from MASLD to MASH. Knowing whether increased exposure time to AAA-1 could lead to end stage disease (including cirrhosis and HCC), and if this could apply to humans as well warrant further investigations.

Metabolic profile of prepartum dairy cows and its influence on the immediate postpartum period, colostrum quality and passive immunity transference

The objective of this study was to evaluate which biochemical markers in the prepartum period of dairy cows influence the immediate postpartum period, the quality of colostrum, and the passive immunity transference in the calves. The experiment was performed on a commercial dairy farm with 52 pregnant multiparous Holstein cows. Animals that gave birth to twins or males were discarded from the experiment. On days −20 of the expected calving date and 24 hours after calving, blood collections, body condition score assessments, and animals weighing were performed. Blood samples from calves were performed 24 hours after colostrum intake. Calf plasma was used to estimate the passive immunity transfer by % brix and total plasma proteins (TPP). In the principal component analysis, it was shown that postpartum NEFA and BHBA was higher in cows with higher prepartum urinary pH and Ca lower prepartum. The cows with the highest NEFA and BHBA in pre and postpartum were the ones that had the lowest % brix in the colostrum. The % brix of the cow’s colostrum directly influenced the % brix and TPP of the calves. The NEFA in the cows prepartum negatively influenced the markers of immunity, the higher the NEFA, the lower the % brix of the cows’ colostrum, % brix of the calves, and TPP. In multivariate regression analyses it was shown that pre-calving NEFA was the marker that most influenced post-calving cow markers and calf % brix, along with colostrum time and % brix of the colostrum (P= 0.0092; r2= 0.83). Cows with higher values NEFA in the prepartum had lower calcemic in the immediate postpartum period. Prepartum NEFA was the marker that most influenced the cows’ immediate postpartum period, being directly related to Ca serum, and also to the passive immunity transference.