Passive Antibody Research Articles

Neonatal Immunization Strategies: Balancing Safety, Efficacy, and Long-Term Immune Programming

Neonatal immunization is a critical public health strategy designed to protect infants from infectious diseases during the vulnerable early stages of life. However, the neonatal immune system exhibits unique characteristics that present challenges in vaccine design, efficacy, and safety. Factors such as maternal antibody interference, immature antigen-presenting cell function, and limited adaptive immune responses necessitate innovative approaches to optimize immunization strategies. This review explores current neonatal vaccination practices, emphasizing the role of adjuvants, novel vaccine platforms, and immune-modulating strategies in enhancing vaccine efficacy. Advances in systems immunology, controlled antigen exposure, and tailored adjuvant formulations have shown promise in overcoming immune limitations while ensuring safety. Additionally, maternal immunization, passive antibody transfer, and neonatal immune programming are discussed as key strategies to bridge early-life susceptibility. Recent developments in nanotechnology and mRNA vaccine platforms also offer potential breakthroughs in neonatal vaccine efficacy. Future research should prioritize refining immunization schedules, developing vaccines specifically tailored to neonatal immune responses, and investigating long-term immune programming effects. A comprehensive understanding of neonatal immunology and innovative vaccine development will be essential for optimizing protection and improving long-term health outcomes. Keywords: Neonatal immunization, vaccine efficacy, maternal antibody interference, adjuvants, immune programming

Incidence and Timing of Epstein-Barr Virus Whole Blood DNAemia in Epstein-Barr Virus-Mismatched Adult and Pediatric Solid Organ Transplant Recipients.

Epstein-Barr virus (EBV) viral load (VL) monitoring is recommended post-transplant for EBV-mismatched (donor EBV seropositive/recipient EBV seronegative) solid organ transplant (SOT) recipients as a component of post-transplant lymphoproliferative disorder (PTLD) prevention, but the optimal frequency and timing of EBV VL monitoring remains unknown. In this retrospective cohort study, we investigated the incidence and timing of whole blood EBV DNAemia in EBV-mismatched adult and pediatric SOT recipients, who had EBV VL monitoring as part of a pre-emptive approach to PTLD prevention to optimize monitoring algorithms. We explored associations between donor-acquired EBV DNAemia (DA-EBV), defined as EBV DNAemia within 1year post-transplant, and donor and recipient characteristics, and determined the proportion who developed PTLD. We analyzed 257 D+/R- recipients (kidney n = 64, heart n = 75, liver n = 93, lung n = 25); 126/257 (49.0%) developed DA-EBV at a median of 83days (Q1-Q3: 50-130days) post-transplant. Incidence of DA-EBV varied by organ and was highest in liver (62.4%) and lowest in heart recipients (28.0%). PTLD was diagnosed in 38/257 (14.8%) EBV-mismatched recipients, 25/162 (15.4%) children, and 13/95 (13.7%) adults. DA-EBV was uncommon in recipients less than 6months old (3/29, 10.3%) and among recipients less than 12months with donors less than 12months (2/29, 6.9%); possible mechanisms of protection other than recipient passive maternal antibody and false-positive donor serostatus are discussed. Monitoring for DA-EBV should be focused on months 2-6 post-transplant. Less frequent whole blood EBV VL monitoring is likely a safe option in recipients less than 6months old and recipients 6-12months old with donors less than 12months old.

Fc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variants

Passive antibody therapies, typically administered via parenteral routes, have played a crucial role in the initial response to the COVID-19 pandemic. However, the ongoing evolution of SARS-CoV-2 has revealed significant limitations of this approach, primarily due to mutational escape and the inadequate delivery of antibodies to the upper respiratory tract. To overcome these challenges, we propose a novel prophylactic strategy involving the intranasal delivery of an antibody in combination with an Fc-binding nanodisc. This nanodisc, engineered to specifically bind to the Fc regions of IgG antibodies, served two key functions: extending the antibody's half-life in the larynx and trachea, and enhancing its neutralization efficacy. Notably, Sotrovimab, an FDA-approved monoclonal antibody that has experienced a significant decline in neutralizing potency due to viral evolution, exhibited robust antiviral activity when complexed with the nanodisc against all tested Omicron variants. Furthermore, the Fc-binding nanodisc significantly boosted the antiviral efficacy of the soluble angiotensin-converting enzyme 2 (sACE2) Fc fusion protein, which possesses broad but modest antiviral activity. In ACE2 transgenic mice, the Fc-binding nanodisc protected better than sACE2-Fc alone with two more log reduction in lung viral titer. Therefore, the intranasal Fc-binding nanodisc offers a promising and powerful approach to counteract the diminished antiviral activity of neutralizing antibodies caused by mutational escape, effectively restoring antiviral efficacy against various evolving SARS-CoV-2 variants.

Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.

The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines.

Randomized controlled trial comparing the immunogenicity of experimental Salmonella Dublin siderophore receptor vaccines in calves.

To describe immune responses following administration of experimental Salmonella Dublin siderophore receptor protein (SRP) vaccines in Holstein heifer calves with adequate passive antibody transfer. Calves were randomly assigned to receive placebo, vaccination with S Dublin SRP in adjuvant A, or vaccination with S Dublin SRP in adjuvant B at 7 ± 3 days of age and 3 weeks later. Before each vaccination, 4 and 8 days after the second vaccination (postvaccination), and 61 to 91 days postvaccination, S Dublin antibody titers were measured. Blood mononuclear cells isolated from blood collected 4 and 8 days postvaccination were stimulated with S Dublin SRP antigen (1 or 5 µg/mL) or positive or negative controls, then analyzed to quantify S Dublin SRP-responsive cells. Cultures of blood mononuclear cells were similarly stimulated to quantify interferon-γ (IFN-γ)-producing and IL-17-producing cells. The trial spanned September 4, 2022, through January 15, 2023. 78 calves were enrolled. Vaccinates had significantly higher IFN-γ-producing cells and IFN-γ and IL-17 concentrations at 4 and 8 days postvaccination, except IFN-γ concentration at day 4 after stimulation with 1 µg/mL. Vaccinates also had higher S Dublin titers at 8 and 61 to 90 days postvaccination. No differences in health events were noted. Vaccination can induce S Dublin SRP-specific humoral and cellular immune responses in Holstein heifer calves. Vaccination with SRP vaccines resulted in immune responses that may help mitigate S Dublin infection. Further research is needed to determine whether vaccination will be protective against S Dublin challenge.

Vaccine and therapeutic agents against the respiratory syncytial virus: resolved and unresolved issue.

Respiratory syncytial virus (RSV) is a predominant pathogen responsible for respiratory tract infections among infants, the elderly, and immunocompromised individuals. In recent years, significant progress has been made in innovative vaccines and therapeutic agents targeting RSV. Nevertheless, numerous challenges and bottlenecks persist in the prevention and treatment of RSV infections. This review will provide an overview of the resolved and unresolved issues surrounding the development of vaccines and therapeutic agents against RSV. As of September 2024, three RSV vaccines against acute lower respiratory infections (ALRI) have been approved globally. Additionally, there have been notable progress in the realm of passive immunoprophylactic antibodies, with the monoclonal antibody nirsevimab receiving regulatory approval for the prevention of RSV infections in infants. Furthermore, a variety of RSV therapeutic agents are currently under clinical investigation, with the potential to yield breakthrough advancements in the foreseeable future. This review delineates the advancements and challenges faced in vaccines and therapeutic agents targeting RSV. It aims to provide insights that will guide the development of effective preventive and control measures for RSV.

A novel small molecule phagocytosis inhibitor, KB-208, ameliorates ITP in mouse models with similar efficacy as IVIG.

The characteristic feature of immune cytopenias involves the process of extravascular phagocytosis, wherein macrophages in the spleen and/or liver engage in the destruction of blood cells that have been opsonized by auto- or alloantibodies. Therefore, new treatments that prevent phagocytosis will be advantageous, especially for short-term usage along with alternative options. KB-208, a small molecule drug, previously shown to be efficacious for the in vitro inhibition of phagocytosis was synthesized. A passive antibody mouse model of immune thrombocytopenia (ITP) was used. Three different mouse strains (BALB/c, C57BL/6, CD1) were used to determine the efficacy of KB-208 compared with IVIG to ameliorate the ITP. Toxicity was investigated after 60-day chronic administration of KB-208 by a biochemistry panel, gross necroscopy and histopathology. KB-208 showed similar efficacy to ameliorate the thrombocytopenia compared with IVIG in all three mouse strains. This small molecule drug was effective at 1 mg/kg in ameliorating ITP, in comparison with IVIG at 1000-2500 mg/kg. KB-208 did not affect other blood parameters or elevate serum biochemistry markers of toxicity nor were any abnormal histopathological findings found. KB-208 is similar to IVIG for the amelioration of ITP in multiple mouse strains. Chronic administration of KB-208 for 60 days did not demonstrate in vivo toxicity. These findings indicate that KB-208 is efficacious, without significant in vivo toxicities in mice, and is a potential small molecule candidate for further evaluation to be used in the treatment of ITP and possibly all immune cytopenias where phagocytosis is responsible for the pathophysiology.

Protective antibody concentrations in primary immunodeficiency following infusion with 5% or 10% intravenous immunoglobulin.

Background: Inadequate production of immunoglobulin G (IgG) antibodies renders patients with primary immunodeficiency susceptible to infection by numerous pathogens, some of which can lead to severe asthma exacerbation and possible death. These patients who are immunocompromised are often reliant on intravenous immunoglobulin (IVIG) therapies, which provide passive antibodies against various respiratory pathogens, including measles virus and encapsulated bacteria. Objective: We conducted a subanalysis of data from a multicenter, multinational, phase III, open-label bioequivalence study to compare protective concentrations of IgG antibodies provided by a 5% and a 10% IVIG product in patients with primary immunodeficiency. Methods: Patients on stable 21- or 28-day regimens of previous IVIG products were assigned to receive study treatment (adults: 5% IVIG and 10% IVIG; children: 10% IVIG) at doses of 300-800 mg/kg per infusion. Trough concentrations of total IgG, IgG subclasses, measles-neutralizing antibodies, and IgG against Haemophilus influenzae type b and Streptococcus pneumoniae serotypes were evaluated. Results: A total of 48 patients (33 adults ages 16-55 years; 15 children ages 2-15 years) were enrolled and received treatment. No statistically significant differences in trough concentrations of total IgG, IgG subclasses, measles-neutralizing antibodies, or IgG directed at encapsulated bacteria were observed between the 5% and 10% formulations in analyses by age (adult or pediatric) or infusion schedule (every 21 or 28 days). All evaluated patients had trough IgG concentrations above accepted thresholds for protection against disease. Conclusion: These findings support the conclusion that, at dose levels and infusion schedules prescribed in clinical practice, this 5% and 10% IVIG product provided consistent, predictable, and bioequivalent IgG concentrations for adult and pediatric patients with primary immunodeficiency disease. Both formulations delivered trough antibody concentrations of total IgG, measles-neutralizing antibodies, and antibodies against encapsulated bacteria that are above thresholds accepted as protective.Clinical trial NCT01963143, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link>.

Passive Anti-amyloid Beta Monoclonal Antibodies: Lessons Learned over Past 20 Years.

Alzheimer's disease (AD) is a neurodegenerative disorder that significantly impairs cognitive and functional abilities, placing a substantial burden on both patients and caregivers. Current symptomatic treatments fail to halt the progression of AD, highlighting the urgent need for more effective disease-modifying therapies (DMTs). DMTs under development are classified as either passive or active on the basis of their mechanisms of eliciting an immune response. While this review will touch on active immunotherapies, we primarily focus on anti-amyloid beta monoclonal antibodies (mAbs), a form of passive immunotherapy, discussing their multifaceted role in AD treatment and the critical factors influencing their therapeutic efficacy. With two mAbs now approved and prescribed in the clinical setting, it is crucial to reflect on the lessons learned from trials of earlier mAbs that have shaped their development and contributed to their current success. These insights can then guide the creation of even more effective mAbs, ultimately enhancing therapeutic outcomes for patients with AD while minimizing adverse events.

Impact of immunoglobulin preparations on anti-HLA antibody specificity analysis.

Donor-specific antibodies (DSAs) targeting human leukocyte antigens (HLAs) substantially reduce the longevity of transplanted organs. Desensitization of DSA-positive renal transplant recipients is achieved through intravenous administration of immunoglobulin (IVIg). However, the presence and detectability of anti-HLA antibodies in IVIg preparations following administration are not fully understood. We aimed to assess whether immunoglobulin preparations contain anti-HLA antibodies that can be detected as passive antibodies when administered into the body. We evaluated 3 immunoglobulin preparations from different pharmaceutical companies, using anti-HLA class I and II antibody specificity tests and immunocomplex capture fluorescence analysis (ICFA). Direct testing for anti-HLA antibodies resulted in high background errors, particularly for Venoglobulin. Diluting Venoglobulin to physiological concentrations revealed the presence of anti-HLA class I antibodies; however, no common alleles were found between the specificity identification test and ICFA.For Glovenin and Venilon, anti-HLA class I and II antibodies were detected; however, variability was observed across different test reagent lots. Moreover, dilution of the globulin formulation revealed a prozone phenomenon. The administration of IVIg complicates the accurate detection of anti-HLA antibodies, underscoring the need for careful interpretation of test results post-IVIg administration.

Assessing hepatitis B virus serologies when transitioning patients from intravenous immune globulin therapy to rituximab for the treatment of autoimmune neuromuscular diseases.

Intravenous immune globulin (IVIG) has been used as early treatment for autoimmune neuromuscular diseases, but due to cost and frequency, may be switched to rituximab. Rituximab and other B-cell-depleting medications require screening of hepatitis B virus (HBV) serologies given the risk of HBV reactivation (HBVr). We aimed to describe the incidence and characteristics of passively transferred antiviral serologies from IVIG and how to differentiate between passive antibody transfer and resolved HBV infection. This was a single-center descriptive study of neurology patients prescribed rituximab and IVIG. Retrospective medical record reviews were performed and patient-specific variables were collected. Twelve patients had reactive anti-HBc results after starting IVIG, but only 9 were confirmed to have reactive anti-HBc from passive transfer. Whether reactive anti-HBc in the remaining three patients was from passive IVIG transfer could not be confirmed. Five patients with reactive anti-HBc results during rituximab screening did not have pre-IVIG anti-HBc results for comparison and were started on antiviral prophylaxis. Reactive anti-HBc serologies changed to nonreactive after IVIG discontinuation 44-321 days after the last IVIG infusion. This study confirms IVIG can passively transfer anti-HBc serologies in a neurologic cohort. Ideally, HBV serologies would be checked before starting IVIG to help later determine if passive transfer occurred. With the increasing use of B-cell-depleting medications for neuromuscular conditions, it is important for providers to be knowledgeable on the interpretation of HBV serologies for patients on IVIG and to ensure implementation of an HBVr prophylaxis management strategy for patients when appropriate.

The role of convalescent plasma and hyperimmune immunoglobulins in the COVID-19 pandemic, including implications for future preparedness.

When Coronavirus Disease-19 (COVID-19) struck the world in December 2019, initiatives started to investigate the efficacy of convalescent plasma, a readily available source of passive antibodies, collected from recovered patients as a therapeutic option. This was based on historical observational data from previous virus outbreaks. A scoping review was conducted on the efficacy and safety of convalescent plasma and hyperimmune immunoglobulins for COVID-19 treatment. This review included the latest Cochrane systematic review update on 30-day mortality and safety. We also covered use in pediatric and immunocompromised patients, as well as the logistic challenges faced in donor recruitment and plasma collection in general. Challenges for low resource countries were specifically highlighted. A major challenge is the high donation frequency required from first-time donors to ensure a safe product, which minimizes the risk of transfusion-transmitted infectious. This is particularly difficult in low- and middle- income countries due to inadequate infrastructure and insufficient blood product supplies. High-certainty evidence indicates that convalescent plasma does not reduce mortality or significantly improve clinical outcomes in patients with moderate to severe COVID-19 infection. However, CCP may provide a viable treatment for patients unable to mount an endogenous immune response to SARS-CoV-2, based on mostly observational studies and subgroup data of published and ongoing randomized trials. Convalescent plasma has been shown to be safe in adults and children with COVID-19 infection. However, the efficacy in pediatric patients remains unclear. Data on efficacy and safety of CCP are still underway in ongoing (randomized) studies and by reporting the challenges, limitations and successes encountered to-date, research gaps were identified to be addressed for the future. This experience serves as a valuable example for future pandemic preparedness, particularly when therapeutic options are limited, and vaccines are either being developed or ineffective due to underlying immunosuppression.

Triple Combinations of AAV9-Vectors Encoding Anti-HIV bNAbs Provide Long-Term In Vivo Expression of Human IgG Effectively Neutralizing Pseudoviruses from HIV-1 Global Panel.

Anti-human immunodeficiency virus (HIV) broadly neutralizing antibodies (bNAbs) offer a promising approach for the treatment of HIV-1. The current paradigm for antibody therapy involves passive antibody transfer, requiring regular delivery of bNAbs in treating chronic diseases such as HIV-1. An alternative strategy is to use AAV-mediated gene transfer to enable in vivo production of desirable anti-HIV-1 antibodies. In this study, we investigated two sets of triple combinations of AAV9-vectors encoding different bNAbs: N6, 10E8, 10-1074 (CombiMab1), and VRC07-523, PGDM1400, 10-1074 (CombiMab2). We used CBAxC57Bl and C57BL/6 mouse models to characterize rAAV-induced antibody expression and to evaluate the neutralization capacity of mouse sera against a global panel of HIV-1 viral strains. rAAV9-mediated IgG expression varied between bNAb clones and mouse strains, with C57BL/6 mice exhibiting higher bNAb titers following rAAV delivery. Although CombiMab2 treatment elicited a higher IgG titer than CombiMab1, both combinations resulted in neutralization of all the viral strains from the global HIV-1 panel. Our data highlight the potential of AAV vectors as a long-term option for HIV-1 therapy.

Convalescent Plasma and Other Antibody Therapies for Infectious Diseases-Lessons Learned from COVID-19 and Future Prospects.

Antiviral passive antibody therapy includes convalescent plasma, hyperimmune globulin, and monoclonal antibodies. Passive antibodies have proven effective in reducing morbidity and mortality for SARS-CoV-2 and other infectious diseases when given early in the disease course with sufficiently high specific total and neutralizing antibody levels. Convalescent plasma can be delivered to patients before vaccination implementation or novel drug production. Carefully designed and executed randomized controlled trials near the pandemic outset are important for regulatory bodies, healthcare workers, guideline committees, the public, and the government. Unfortunately, many otherwise well-designed antibody-based clinical trials in COVID-19 were futile, either because they intervened too late in the disease or provided plasma with insufficient antibodies. The need for early treatment mandates outpatient clinical trials in parallel with inpatient trials. Early outpatient COVID-19 convalescent plasma transfusion with high antibody content within 9days of symptom onset has proven effective in blunting disease progression and reducing hospitalization, thus reducing hospital overcrowding in a pandemic. Convalescent plasma offers the opportunity for hope by enabling community participation in outpatient curative therapy while monoclonal therapies, vaccines, and drugs are being developed. Maintaining the appropriate infrastructure for antibody infusion in both outpatient and inpatient facilities is critical for future pandemic readiness.

Varicella-Zoster Virus Pretransplant Vaccination and Posttransplant Infections Among Pediatric Solid Organ Recipients in the Two-Dose Varicella Era: A Single-Center, Multi-Organ Retrospective Study.

Varicella-zoster virus (VZV) pretransplant immunization rates, exposures, and posttransplant disease are poorly characterized among pediatric solid organ transplant (SOT) recipients in the two-dose varicella vaccine era. A retrospective analysis of the electronic health records among children <18 years old who received SOT from January 1, 2011 through December 31, 2021, was performed at a single center to assess for missed pretransplant varicella vaccination opportunities, characterize VZV exposures, and describe posttransplant disease. Among 525 children, 444 were ≥6 months old (m.o.) at SOT with a documented VZV vaccine status. Eighty-five (19%) did not receive VZV Dose One; 30 out of 85 (35%) could have been immunized. Infants 6-11 m.o. accounted for 14 out of 30 (47%) missed opportunities. Among children ≥12 m.o. with documented Dose Two status (n = 383), 72 had missed vaccination opportunities; 57 out of 72 (79%) were children 1-4 years old. Most children had unclassifiable pre-SOT serostatus as varicella serology was either not obtained/documented (n = 171) or the possibility of passive antibodies was not excluded (n = 137). Of those with classified serology (n = 188), 69 were seroimmune. Forty-seven of 525 (9%) children had recorded VZV exposures; two developed varicella-neither had documented pre-SOT seroimmunity nor had received post-exposure prophylaxis. Nine additional children had medically attended disease: four primary varicella and five zoster. Of the 11 cases, 10 had cutaneous lesions without invasive disease; one had multi-dermatomal zoster with transaminitis. Seven (64%) received treatment exclusively outpatient. VZV exposure and disease still occur. Optimizing immunization among eligible candidates and ensuring patients have a defined VZV serostatus pretransplantation remain goals of care.

Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.

The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n=6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines.

Foals of mares vaccinated for Hendra virus have a suboptimal response to HeV vaccination

Hendra virus (HeV) is lethal to horses and a zoonotic threat to humans in Australia, causing severe neurological and/or respiratory disease with high mortality. An equine vaccine has been available since 2012. Foals acquire antibodies from their dams by ingesting colostrum after parturition, therefore it is assumed that foals of mares vaccinated against HeV will have passive HeV antibodies circulating during the first several months of life until they are actively vaccinated. However, no studies have yet examined passive or active immunity against HeV in foals. Here, we investigated anti-HeV antibody levels in vaccinated mares and their foals. Testing for HeV neutralising antibodies is cumbersome due to the requirement for Biosafety level 4 (BSL-4) containment to conduct virus neutralisation tests (VNT). For this study, a subset of samples was tested for HeV G-specific antibodies by both an authentic VNT with infectious HeV and a microsphere-based immunoassay (MIA), revealing a strong correlation. An indicative neutralising level was then applied to the results of a larger sample set tested using the MIA. Mares had high levels of HeV-specific neutralising antibodies at the time of parturition. Foals acquired high levels of maternal antibodies which then waned to below predictive protective levels in most foals by 6 months old when vaccination commenced. Foals showed a suboptimal response to vaccination, suggesting maternal antibodies may interfere with active vaccination. The correlation analysis between the authentic HeV VNT and HeV MIA will enable further high throughput serological studies to inform optimal vaccination protocols for both broodmares and foals.

Alpha-Synuclein Targeting Monoclonal Antibody Therapy Treatment for Parkinson’s Disease

An investigation was done on plausible antibody treatments for alpha-synuclein, which is an instigator for the dopamine-lacking neurodegenerative disease Parkinson’s to occur in patients due to its aggregation. Trials working towards slowing the pathogenesis of Parkinson’s Disease through monoclonal antibodies for alpha-synuclein were analyzed. Previously, similar therapies were done in other neurodegenerative diseases like Alzheimer’s, allowing for a hopeful hypothesis in Parkinson’s. Active and Passive antibody treatments were compared and discussed: Pranizeumab, Cipanemab, PD01A, and UB-312. Trials often found success in animal models and not the same outcome in humans within the passive studies. In active studies, however, more hopeful results were presented, showing built immunity towards alpha-synuclein and enhancement of motor symptoms. Though some studies led to a dead end, studies use information to complete future phases. Monoclonal antibody treatment for Parkinson’s Disease is a real future in the fight for reducing the pathogenesis of Parkinson’s Disease.

Immune response and protection of neonatal, colostrum-fed calves with modified live, intranasal, tri-valent vaccine using an experimental challenge with virulent bovine respiratory syncytial virus

Bovine respiratory syncytial virus (BRSV) is major viral con­tributor to bovine respiratory disease (BRD). BRD is a major cause of morbidity and mortality in all classes of cattle but par­ticularly young beef and dairy calves. Passive antibodies not only help protect the calf against infection, but may interfere with the immune responses following vaccination. The objective of this study was to evaluate the efficacy and immune response of an intranasal modified live virus (MLV) trivalent vaccine in the presence of well-defined maternal passive immunity.

Acetylcholine Binding Receptor Positivity from Passive Antibody Transfer in a Case of Progressive Muscular Atrophy (P11-11.009).

Not applicable. Extraocular movements are typically preserved in motor neuron disease, at least in the early course and can be a helpful differentiator from myasthenia gravis. Exceedingly rare cases of concomitant myasthenia gravis with motor neuron disease were described. Not applicable. A 54-year-old man presented with progressive shortness of breath over 9-months and bilateral hand weakness over 2-months and was treated with a single round of intra-venous immunoglobulin (IVIG) elsewhere prior to his transfer to our facility. Initial neurological examination revealed respiratory muscle usage, fasciculations, and bilateral intrinsic muscle weakness without hyperreflexia. Of importance, no extraocular movement impairment was noted at the time. A provisional diagnosis of progressive muscular atrophy was made based on the electrodiagnostic testing pending neuroimaging. But a positive acetylcholine receptor binding antibody (AchRB-ab) was noted. Two weeks later at his re-admission, he complained of double vision and noted to have asymmetric ocular abduction paresis, along with worsening respiratory failure necessitating intubation. Repeat electromyography confirmed previous findings, while paraneoplastic/autoimmune-antibodies, spinal fluid analysis, MRI brain and pan-spine were unremarkable. Ocular abduction paresis improved post plasma-exchange but continued needing long-term ventilatory support at three-week follow-up. It should be noted that his acetylcholine receptor antibodies were negative prior to his IVIG and importantly on repeat testing (sent to two independent commercial labs) prior to initiated plasma-exchange. Initially, we entertained the idea of a false-positive AchRB-ab result due to the inability to replicate it. However, the presence of ocular symptoms, coupled with extra-ocular movement impairment that responded to plasma-exchange, led us to suspect symptomatic myasthenia gravis caused by passive antibody transfer from IVIG. While passive antibody transfer post-IVIG has been reported for other antibodies, it has not been described for AchRB-ab. Disclosure: Dr. Roberts has nothing to disclose. Dr. Cohn has nothing to disclose. Dr. Sista has nothing to disclose.