Passive Immunization Research Articles

Role of Antibodies and Their Specificities in Atherosclerotic Cardiovascular Disease.

Atherosclerosis is a lipid-driven chronic inflammatory disease that is modulated by innate and adaptive immunity including humoral immunity. Importantly, antibody alterations achieved by genetic means or active and passive immunization strategies in preclinical studies can improve or aggravate atherosclerosis. Additionally, a wide range of epidemiological data demonstrate not only an association between the total levels of different antibody isotypes but also levels of antibodies targeting specific antigens with atherosclerotic cardiovascular disease. Here, we discuss the potential role of atherogenic dyslipidemia on the antibody repertoire and review potential antibody-mediated effector mechanisms involved in atherosclerosis development highlighting the major atherosclerosis-associated antigens that trigger antibody responses.

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 24hours after calving, blood collections, body condition score assessments, and animals weighing were performed. Blood samples from calves were performed 24hours 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.

Passive immunoprophylaxis with Ccombodies against Vibrio parahaemolyticus in Pacific white shrimp (Penaeus vannamei)

The Vibrio parahaemolyticus strain causing acute hepatopancreatic necrosis disease (AHPND) in shrimp secretes toxins A and B (PirAVp/PirBVp). These toxins have been implicated in pathogenesis and are targets for developing anti-AHPND therapeutics or prophylactics that include passive immunization. We have previously reported that Ccombodies (recombinant hagfish variable lymphocyte receptor B antibodies; VLRB) targeting PirBVp conferred protection against V. parahaemolyticus in shrimp when administered as a feed supplement. In this study, we screened a phage-displayed library of engineered VLRBs for PirAVp-targeting Ccombodies that were mass-produced in a bacterial expression system. We then introduced these Ccombodies into the diet of Pacific white shrimp (Penaeus vannamei) over a seven-day period. Subsequently, the shrimp were exposed to a challenge with V. parahaemolyticus. Mortality rates were then observed and recorded over the following seven days. Administering shrimp feed supplemented with Ccombodies at a high dose (100 mg per 100 g feed) reduced mortality in recipient animals (2.96-5.19%) statistically similar to mock-challenged control (1.48%), but significantly different from the Ccombody-deficient control (74.81%). This suggests that the Ccombodies provided strong protection against the bacterium. Feeding shrimp with a median dose (10 mg/100 g feed) gave statistically comparable low mortality (5.93-6.67%) as the high dose. Reducing the Ccombody dose to 1 mg/100 g feed showed variable effects. Ccombody A2 showed mortality (11.85%) significantly lower than that of the Ccombody-deficient group (74.81%), suggesting that it can effectively protect against the bacterial challenge at a low dose. Our results demonstrate the ability of the phage-displayed VLRB library to generate antigen-specific Ccombodies rapidly and simply, with the expression of high protein levels in bacteria. The protective effect provided by these Ccombodies aligns with our earlier results, strongly supporting the use of VLRB antibodies as a substitute for IgY in passive immunoprophylaxis against AHPND in shrimp.

Analysis of colostral antibodies to herpesvirus 1 and 5 in Murrah buffalo calves

Familiar agriculture is predominant in the production of milk buffaloes in São Paulo southwest, Brazil. The production of buffaloes’ milk is sold almost exclusively to cheese production inside and out São Paulo State. This search was done in a proprerty located in Alambari, São Paulo, specialized in the production of Murrah buffaloes, with 21 animals, born between March and May in the year 2017. Blood was collected at 24 to 48 h from the birth, every 15 days and at the completetion of weaning (91 days of age). The samples were collected in vaccum tubes of 10 mL with coagulum activator, by a puncture of the jugular vein. With the application of the virus neutralization tests, we could see 90.47% reagent animals for BoHV-5 and or BoHV-1 in the first two days of life. The geometric medium titles (GMT) of antibodies reduced significantly from the time 0 (1.4563) to the time 6 (05721) (P=0.0001), showing adequate transference of passive immunity through the ingestion of colostrum by buffalo calves, with the persistence of antibodies until 3 months old. Considering that most buffalo calves were reagents after sucking the colostrum, it is possible to conclude that there is a great occurrence of BoHV-5 and or BoHV-1 once there is a crossed reaction among these and the cattle with no historic of vaccination for the agents.

Passive protection of chicken egg yolk immunoglobulin (IgY) against Streptococcus agalactiae infection in Nile tilapia (Oreochromis niloticus)

IgY is an immunoglobulin primarily found in the serum and egg yolk of birds, amphibians, and reptiles. Recent years, IgY is considered to have a good application prospect in the immunodiagnostics and passive immunotherapy of aquatic diseases. In this study, we prepared a specific IgY against Streptococcus agalactiae in tilapia after immunizing the hens for 4 times. The result of ELISA detection showed that the IgY titers in water-soluble fraction (WSF) after 6 weeks of immunization reached 1:51200 and last for 4 weeks. Western blot (WB) analysis data showed that the specific IgY could recognize the target band, the specific IgY showed a concentration-dependent inhibitory effect on the growth of S. agalactiae, altered cell wall structure and aggluted of S. agalactiae. The quantitative reverse transcription PCR (qRT-PCR) analysis data suggested that the specific IgY downregulated the expression of pro-inflammatory factors (IL-8, TNF-α), upregulated the anti-inflammatory factors (IL-10, TGF-β). In addition, the histopathological results showed that the specific IgY significantly decreased the pathological manifestations, dramatically improved the survival rates of tilapia in injection, feeding, and immersion experiments. Collectively, our findings demonstrated that the broad potential of specific IgY for the prevention and treatment of S. agalactiae infection in tilapia.

A Monoclonal Antibody with a High Affinity for Ricin Isoforms D and E Provides Strong Protection against Ricin Poisoning.

Ricin is a highly potent toxin that has been used in various attempts at bioterrorism worldwide. Although a vaccine for preventing ricin poisoning (RiVax™) is in clinical development, there are currently no commercially available prophylaxis or treatments for ricin intoxication. Numerous studies have highlighted the potential of passive immunotherapy using anti-ricin monoclonal antibodies (mAbs) and have shown promising results in preclinical models. In this article, we describe the neutralizing and protective efficacy of a new generation of high-affinity anti-ricin mAbs, which bind and neutralize very efficiently both ricin isoforms D and E in vitro through cytotoxicity cell assays. In vivo, protection assay revealed that one of these mAbs (RicE5) conferred over 90% survival in a murine model challenged intranasally with a 5 LD50 of ricin and treated by intravenous administration of the mAbs 6 h post-intoxication. Notably, a 35% survival rate was observed even when treatment was administered 24 h post-exposure. Moreover, all surviving mice exhibited long-term immunity to high ricin doses. These findings offer promising results for the clinical development of a therapeutic candidate against ricin intoxication and may also pave the way for novel vaccination strategies against ricin or other toxins.

Management of RSV Bronchiolitis in Outpatient Setting

AbstractSeasonal respiratory syncytial virus (RSV) lower respiratory infections (RSV-LRI) and bronchiolitis in children remain a high burden to medical facilities. Studies evaluating the practical approach in outpatient settings are scarce. We conducted a survey to provide an insight into management in pediatric offices in Germany. Invitations for participation in an online survey were sent to 623 providers of pediatric primary care via email. Recipients were randomly chosen from national databanks based on zip codes. The response rate was 16,2%, n=92 (14,7%) questionnaires were fully answered and analyzed. 93,5% (n=86) are board certified pediatricians. In outpatient setting, every second patient with suspected or confirmed RSV-LRI is presented three times or more. 40,7% of our participants refer less than 10% of all patients to hospital, 83,7% refer less than one third (<30%). 33,7% of all participants never perform virological testing in suspected cases of RSV-LRI. More than 50% of all participants prescribe bronchodilators, hypertonic saline inhalation is prescribed by 17,4%. Antibiotics are prescribed in less than 10% of all cases of RSV-LRI. About 3/4 ask for a clearer, more conclusive guideline regarding prophylaxis. The diagnostic approach varies significantly. Although not recommended in international guidelines, bronchodilators are still frequently used. Considering emerging options for passive immunization, broader inclusion criteria into immunization regimes are requested by the participants. More conclusive guidelines and recommendations could further improve the management of outpatient RSV-LRI in children.

PSIV-24 Evaluation of different colostrum feeding volumes on serum immunoglobulin G concentration and metabolic profiles of calves in high altitude area

Abstract Qinghai-Tibet Plateau is the highest plateau in the world, reputed as “the roof of the world” and “the world’s third pole”. Its ecological environment is characterized by low atmospheric oxygen pressure, cold, and limited feed supplies. This study aimed to investigate the serum immunoglobulin G (IgG) concentration and metabolic profiles of calves in high altitude area (3,650 m) fed different volumes of colostrum [8, 12, or 15% of birth body weight (BW)] using untargeted metabolomics strategies. Neonatal Holstein hybrid heifer calves (n = 44) were randomly divided into 1 of the 3 colostrum feeding amounts: 8% of birth BW (Low volume, L), 12% of birth BW (Middle volume, M), and 15% of birth BW (High volume, H) in colostrum. To safeguard the efficiency of colostrum intake, the colostrum was fed to calves within 0.5 h and 6 h after birth. The serum samples at 24 h after birth were collected for IgG concentration determination by indirect enzyme-linked immunosorbent assay (ELISA) and for LC-MS/MS metabonomic analysis. As the volumes of colostrum increased, there was a linearly increased in the serum IgG concentration (P < 0.01). Differential metabolites were selected according to the following 3 conditions: minimum fold change (FC) > 2, P-value < 0.01 in single-dimensional statistical analysis, and variable importance in projection (VIP) > 1 in the OPLS-DA model. Multivariate statistical analyses were performed to visualize differences among groups. Based on the screening criteria, a total of 3 differential metabolites (22 alpha-Hydroxy-campesterol, N-Myristoyl Histidine, and Calcitetrol) were detected between L and M, of which all differential metabolites were down-regulated. Six differential metabolites were detected between M and H, of which PC[P-18:1(11Z)/18:1(12Z)-2OH(9,10)] was up-regulated and 5 differential metabolites including 1-arachidonoyl-2-hydroxy-sn-glycero-3-phosphate, propanoyl phosphate, ascorbic acid 6-palmitate, 20-hydroxyecdysone, and 6’’’-deamino-6’’’-hydroxyparomomycin II were down-regulated. There were 28 differed metabolites (including leucyl-tryptophan, calcitetrol, 3’’-Oxoribostamycin) between L and H, of which 9 differential metabolites were up-regulated and 19 differential metabolites were down-regulated (Figure 1). Based on KEGG metabolic enrichment pathway analysis and pathway topology analysis, porphyrin metabolism was identified as the most impacted pathway between L and H (Figure 2). In conclusion, increasing colostrum volumes significantly increased serum IgG concentrations at 24 h after birth, favoring the success of the transfer of passive immunity. Alterations in serum metabolome of calves in the Qinghai-Tibet Plateau fed different volumes of colostrum were successfully revealed by untargeted metabolomics. The role of the identified differential metabolites and enriched pathway in the transfer of passive immunity in calves at high altitude deserves further investigation. Keywords: calf, colostrum volumes, high altitude area

108 Early colostrum uptake by the newborn requires prepartum initiation of lactogenesis in ungulate species - Sponsored by EAAP

Abstract Due to anatomical characteristics of ungulate placenta types, immunoglobulins (IG) cannot be transferred via the placenta from the maternal to the fetal circulation during pregnancy. Therefore, passive immunization of the newborn ungulate immediately after birth is crucial for its survival. Colostrum, the first milk produced contains immunoglobulins (IG) as well as greater concentrations of several nutrients and bioactive components to provide specific immunity for the first weeks of life as well as an activation of the digestive tract and metabolism through colostral hormones, growth factors, vitamins, and special nutrients such as oligosaccharides. The uptake of colostrum by newborn calves, piglets, or foals within the first few hours after birth requires the availability of colostrum in a sufficiently liquid form. The formation of pre-colostrum starts days or even weeks before parturition, which allows concentrations of IG and other factors far beyond the concentrations in maternal blood circulation. Pre-colostrum components are partially secreted into the alveolar lumen and partially stored in the lactocytes of the mammary gland. These secretions are characterized by increased viscosity and density, which are difficult to harvest by the newborn. Through lactogenesis the secretion of milk components such as lactose is initiated, which causes a considerable water influx into the mammary secretion through an osmotic gradient between maternal blood and mammary secretion. The typical high concentrations of gestagens, mostly progesterone, inhibit the initiation of lactogenesis during pregnancy. A declining gestagen activity is the key signal to initiate a lactogenic prolactin increase and hence milk secretion. Mechanisms and timing of gestagen withdrawal differ considerably among mammalian species. Most species initiate both parturition and lactation through luteolysis (cattle, goat, pig, cat, dog, rabbit, mouse rat). In some species the placenta takes over the main portion of gestagen production (human, sheep, horse). In human, IG are transferred to the fetus during pregnancy, and the start of colostrum secretion only several days after parturition is no problem. In sheep and horses, gestagen secretion during late pregnancy is provided by the placenta. Both of these species are ungulates, and a delayed start of lactogenesis would be critical for the survival of the newborn. Therefore, the placental steroid secretion is subject to characteristic changes in both species towards the end of pregnancy to allow a timely availability of colostrum immediately after birth. At the end of pregnancy, the placenta of sheep produces estrogens at the expense of progesterone, and in horses the less potent dihydroprogesterone is produced instead of progesterone. A considerable variation in the resulting colostrum composition is likely due to the existing wide range of the interval between the commencement of lactogenesis and parturition or due to local regulatory effects at the level of individual glands.

247 Interaction between colostrum and milk replacer supply on growth, development and fecal consistency of dairy surplus calves

Abstract This study examined the interactions between early life nutrition strategies and their impact on growth, development, and fecal consistency in surplus bull calves. Holstein-Friesian bull calves [n = 120; body weight (BW) = 43.1±3.56 kg] were enrolled. In the first 12 h after birth, calves were fed either 2 L (100 g of IgG) or 6L (300 g of IgG) of colostrum replacer (CR) to obtain either failure (F) or successful (S) transfer of passive immunity, respectively. Upon arrival at the facility, serum IgG concentrations were measured; therefore, F and S calves were identified accordingly and randomly assigned to one of two milk replacer (MR) feeding schemes: Moderate (Mod; ~8 L) or Low (Low; ~4 L). In total, there were 4 treatments resulting from the 2 × 2 factorial design: F-Mod, F-Low, S-Mod, S-Low (n = 30/treatment). Calves were individually housed and fed twice daily until d 42, gradually weaned until d 56, and had free access to straw and water during the study. On d 22, a calf pelleted starter was offered. To evaluate organ and gastroinstetinal tract development, 10 calves/treatment were euthanized at 84 d of age. Other measurements include weekly BW, daily intakes, and daily fecal score until d 21. Data were analyzed by PROC MIXED in SAS accounting for the fixed effects of block, CR, MR, and time, and their interaction. Time entered the model as a repeated statement, and initial BW was used as a covariable when appropriate. Initial BW was not different across treatments, whereas serum IgG was greater in S calves (S = 1,962.9 vs. F = 941.0 mg IgG/dL). During the study, BW was influenced by both CR (P = 0.001) and MR (P < 0.001), where S and Mod calves consistently exhibited greater BW when compared with F and Low calves, respectively. At d 84, Mod calves (F-Mod and S-Mod) were on average 18 kg heavier than Low calves. Similarly, Mod calves exhibited greater fresh tissue weights in the liver, pancreas, spleen, and both the small and large intestines (P < 0.05). Starter intake was influenced by MR (P < 0.001), with Low calves having the greatest intake before and during weaning. However, post-weaning starter intake was greater (P = 0.010) in Mod calves. Fecal consistency was influenced by CR (P = 0.001) and MR (P < 0.001), with S and Low calves having improved fecal consistency. Although no interactions were observed between CR and MR, these findings underscore the importance of considering both colostrum and MR levels in calf nutrition management to optimize growth and improve animal welfare during the early stages of life.

111 Factors affecting transfer of passive immunity in beef calves

Abstract Data from 9 calving experiments were used to investigate relationships of dam, calf, and colostrum factors with passive transfer in beef calves. Serum was collected at 48.33 ± 1.25 (SD) h of age for 313 calves, and single rear quarter colostrum yields were determined pre-suckling for dams of 117 calves. Serum and colostrum IgG concentrations were determined by ELISA. Relationship of serum IgG with colostrum variables was determined using Pearson correlation coefficients. Serum IgG was positively correlated (P ≤ 0.002) with colostrum IgG (r = 0.47) and protein (r = 0.45) concentrations and colostrum total IgG (r = 0.28) but tended to be negatively correlated (r = -0.17, P = 0.06) with colostrum yield. Based on passive transfer thresholds in the literature, 3 calves (0.96%) had < 8 mg/mL serum IgG, 16 calves (5.1%) < 16 mg/mL, and 43 calves (13.7%) had < 24 mg/mL. For this analysis, calves with serum IgG < 24 mg/mL at 48 h were considered to have failure of passive transfer (FPT). Continuous variables (dam BW and calf size, 48-h serum chemistry panel, and time to stand) were compared for FPT versus non-FPT calves using a mixed model with FPT class (fixed effect) and experiment (random effect). Calves with FPT had less (P ≤ 0.03) circulating triglycerides, glucose, calcium, magnesium, total protein, globulin, and gamma-glutamyl transferase but greater (P ≤ 0.001) circulating non-esterified fatty acids, sodium, chloride, and total bilirubin than non-FPT. Effects of categorical variables on calf 48-h serum IgG were determined using separate mixed models with variable (fixed) and experiment (random). Primiparous dams gave birth to calves that had less (P = 0.05) serum IgG at 48 h than multiparous dams. Calves born to moderate dams (BCS = 5) had less (P = 0.007) serum IgG than those born to fleshy dams (BCS ≥ 6) and tended to have less (P = 0.08) serum IgG than calves born to thin dams (BCS < 5). Calf sex, calving season, calving difficulty score, and vigor score at 10 min did not affect (P ≥ 0.19) serum IgG. Relationships of calf 48-h serum IgG with continuous variables was also determined using Pearson correlation coefficients, and only r ≥ 0.20 or ≤ -0.20 are reported. Serum IgG was positively correlated (P ≤ 0.005) with 48-h serum total protein (r = 0.75), globulin (r = 0.76), gamma-glutamyl transferase (r = 0.32), and potassium (r = 0.20). Serum IgG was negatively correlated (P < 0.001) with gestation length (r = -0.22) and 48-h serum albumin (r = -0.43), sodium (r = -0.24), and total bilirubin (r = -0.27). Overall, beef calves in this dataset generally had successful passive transfer that was associated with several dam, calf, and colostrum factors.

Vaccines and monoclonal antibodies to prevent healthcare-associated bacterial infections.

SUMMARYHealthcare-associated infections (HAIs) represent a burden for public health with a high prevalence and high death rates associated with them. Pathogens with a high potential for antimicrobial resistance, such as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and Clostridioides difficile, are responsible for most HAIs. Despite the implementation of infection prevention and control intervention, globally, HAIs prevalence is stable and they are mainly due to endogenous pathogens. It is undeniable that complementary to infection prevention and control measures, prophylactic approaches by active or passive immunization are needed. Specific groups at-risk (elderly people, chronic condition as immunocompromised) and also healthcare workers are key targets. Medical procedures and specific interventions are known to be at risk of HAIs, in addition to hospital environmental exposure. Vaccines or monoclonal antibodies can be seen as attractive preventive approaches for HAIs. In this review, we present an overview of the vaccines and monoclonal antibodies in clinical development for prevention of the major bacterial HAIs pathogens. Based on the current state of knowledge, we look at the challenges and future perspectives to improve prevention by these means.

Efficacy evaluation of a bivalent subunit vaccine against epidemic PEDV heterologous strains with low cross-protection.

The detection rate of PEDV G2a subtype strains is currently increasing. Although commercial vaccines are available, most vaccines do not exert an ideal protective effect against these strains. Furthermore, there is no definitive research into the cross-protection between G2a and G2b strains, and no bivalent vaccine provides joint protection against both. Therefore, in this study, we investigated the cross-protection between PEDV G2a and G2b strains and designed a candidate bivalent subunit vaccine combining the trimeric S proteins of the G2a and G2b subtypes. We demonstrate that the cross-protection between strains G2a and G2b is poor and that this bivalent subunit vaccine protects piglets from viral attack by inducing both active and passive immunity. This study emphasizes the effectiveness of the PEDV G2a/G2b-S bivalent subunit vaccine and provides a feasible method for the development of efficient PEDV vaccines.

Virus-like particle-based vaccines targeting the Anopheles mosquito salivary protein, TRIO.

Malaria is a highly lethal infectious disease caused by Plasmodium parasites. These parasites are transmitted to vertebrate hosts when mosquitoes of the Anopheles genus probe for a blood meal. Sporozoites, the infectious stage of Plasmodium , transit to the liver within hours of injection into the dermis. Vaccine efforts are hindered by the complexity of the parasite's lifecycle and the speed at which the infection is established in the liver. In an effort to enhance immunity against Plasmodium , we produced a virus-like particle (VLP)-based vaccine displaying an epitope of TRIO, an Anopheles salivary protein which has been shown to enhance mobility and dispersal of sporozoites in the dermis. Previous work demonstrated that passive immunization with TRIO offered protection from liver infection and acted synergistically with a Plasmodium targeted vaccine. Immunization of mice with TRIO VLPs resulted in high-titer and long-lasting antibody responses that did not significantly drop for over 18 months post-immunization. TRIO VLPs were similarly immunogenic when combined with an anti-malaria vaccine targeting the L9 epitope of the Plasmodium falciparum circumsporozoite protein.However, when used in a malaria challenge mouse model, TRIO VLPs only provided modest protection from infection and did not boost the protection provided by L9 VLPs.

FcRider: a recombinant Fc nanoparticle with endogenous adjuvant activities for hybrid immunization.

Active immunization (vaccination) induces long-lasting immunity with memory, which takes weeks to months to develop. Passive immunization (transfer of neutralizing antibodies) provides immediate protection, yet with high cost and effects being comparatively short-lived. No currently approved adjuvants are compatible with formulations to combine active and passive immunizations, not to mention their huge disparities in administration routes and dosage. To solve this, we engineered the Fc fragment of human IgG1 into a hexamer nanoparticle and expressed its afucosylated form in Fut8-/- CHO cells, naming it "FcRider." FcRider is highly soluble with long-term stability, easily produced at high levels equivalent to those of therapeutic antibodies, and is amenable to conventional antibody purification schemes. Most importantly, FcRider possesses endogenous adjuvant activities. Using SWHEL B cell receptor (BCR) transgenic mice, we found that HEL-FcRider induced GL7+ germinal center B cells and HEL-specific IgG. Similarly, immunizing mice with UFO-BG-FcRider, a fusion containing the stabilized human immunodeficiency virus-1 (HIV-1) Env protein as immunogen, promoted somatic hypermutation and generation of long CDR3 of the IgG heavy chains. Intramuscular injection of (Fba+Met6)3-FcRider, a fusion with two peptide epitopes from Candida albicans cell surface, stimulated strong antigen-specific IgG titers. In three different models, we showed that afucosylated FcRider functions as a multivalent immunogen displayer and stimulates antigen-specific B cells without any exogenous adjuvant. As an antibody derivative, afucosylated FcRider could be a novel platform combining vaccines and therapeutic antibodies, integrating active and passive immunizations into single-modality "hybrid immunization" to provide complete and long-lasting protection against infections, and may open new avenues in cancer immunotherapy as well.

Serum IgA antibody level against porcine epidemic diarrhea virus is a potential pre-evaluation indicator of immunization effects in sows during parturition under field conditions

BackgroundPorcine Epidemic Diarrhea (PED) is a highly contagious disease caused by Porcine Epidemic Diarrhea Virus (PEDV), resulting in a mortality rate of suckling piglets as high as 100%. Vaccination is the primary strategy for controlling PEDV infection, however, there is currently a lack of reliable methods for assessing the efficacy of vaccination. This study aimed to analyze serum and colostrum samples from 75 parturient sows with a specific vaccination strategy to measure levels of IgG, IgA, and neutralizing antibodies (nAbs) against PEDV, and to investigate the correlation between serum and colostrum antibody levels, as well as to identify potential biomarkers that can be used to evaluate immunization effects under field conditions.ResultsThe findings of correlation analysis between antibody levels of IgA, IgG, and nAbs in serum or colostrum samples revealed that IgG demonstrated the most robust correlation with nAbs exhibiting a correlation coefficient of 0.64 in serum samples. Conversely, IgA exhibited the highest correlation with nAbs, with a correlation coefficient of 0.47 in colostrum samples. Additionally, the correlation analysis of antibody levels between serum and colostrum samples indicated that serum IgA displayed the strongest correlation with colostrum IgA, with a coefficient of 0.63, indicating that serum IgA may serve as a viable alternative indicator for evaluating IgA levels in colostrum samples. To further evaluate the suitability of serum IgA as a substitute marker for colostrum IgA, levels of IgA antibodies in serum samples from sows were examined both pre- and post-parturition. The findings indicated that serum IgA levels were initially low prior to the initial immunization, experienced a notable rise 21 days after immunization, and maintained a significant elevation compared to pre-immunization levels from 21 days pre-parturition to 14 days postpartum, spanning a total of 35 days.ConclusionsSerum anti-PEDV IgA antibody levels may serve as a valuable predictor for immunization effects, allowing for the assessment of colostrum IgA antibody levels up to 21 days in advance. This insight could enable veterinarians to timely adjust or optimize immunization strategies prior to parturition, thereby ensuring adequate passive immunity is conferred to piglets through colostral transfer postpartum.

Molecular dynamics simulation of the brain-isolated single-domain antibody/nanobody from camels through in vivo phage display screening.

During the last decade, there has been a significant rise in the use of therapeutic antibodies or passive immunotherapy for treating various conditions like inflammation and cancer. However, these proteins face challenges reaching the brain and often require specialized delivery methods such as single-domain antibodies (sdAbs). Traditional antibodies struggle to efficiently cross the blood-brain barrier (BBB), hindering their effectiveness. Receptor-mediated transcytosis (RMT) offers a promising pathway for transporting large molecules essential for brain function and treatment across the BBB. SdAbs and peptide ligands with an affinity for RMT receptors are commonly employed to enhance the transport of biotherapeutics compounds across the BBB. This research used a sdAbs phage-displayed library from 13 camelus dromedarius samples to identify sdABs that specifically bind to and are internalized by human BBB endothelial cells (ECs) through in vivo panning. One sdAb, defined as FB24, was isolated, sequenced, translated into an open reading frame (ORF), and subjected to three-dimensional (3D) modeling. Molecular docking and molecular dynamics simulations were carried out by the HADDOCK web server and GROMACS, respectively, to evaluate the interaction between FB24 and EC receptors in silico. The docking results revealed that FB24 exhibited binding activity against potential EC receptors with -1.7 to -2.7 ranged z score and maintained a stable structure. The docked complex of FB24-RAGE (receptor for advanced glycation end products, also known as advanced glycation end product receptor [AGER]) showed 18 hydrogen bonds and 213 non-bonded contacts. It was chosen for further analysis by molecular dynamics simulations by GROMACS. This complex showed a stable condition, and its root mean square deviation (RMSD) was 0.218 nm. The results suggest that FB24 could serve as a suitable carrier vector for transporting therapeutic and diagnostic agents across the BBB to the brain through a non-invasive route.

Immunoglobulins as Tools for Passive Immunization in Preventive Healthcare

Immunoglobulins have emerged as an important tool in passive immunization for the prevention and treatment of infectious diseases. Immunoglobulins are the proteins produced by B cells that bind to specific pathogens, neutralize them, and facilitate their removal by the immune system. In preventive healthcare, immunoglobulins are used for primordial, primary, secondary, tertiary, and quaternary prevention of infectious diseases. This work was designed to carry out an extensive literature search to provide useful information on immunoglobulins as the tools of passive immunization in preventive healthcare. Relevant and accurate literatures were sourced from the World Health Organization. Centers for Disease Control and Prevention, National Center for Disease Control, PubMed, Scopus, PLoS One, and NATURE journals: Primordial prevention aims to prevent the emergence and spread of risk factors for infectious diseases. Immunoglobulins can be used to prevent the spread of infectious diseases by targeting the pathogens that cause them. The primary prevention aims to prevent the initial infection of individuals at risk of acquiring infectious diseases. Immunoglobulins can be used as prophylaxis to prevent the onset of infection in high-risk individuals. The secondary prevention aims to reduce the severity and duration of infectious diseases. Immunoglobulins can be used to treat infectious diseases and prevent complications. The tertiary prevention aims to prevent the recurrence and complications of infectious diseases. Immunoglobulins can be used to prevent the recurrence of infections in individuals who have already been infected. Quaternary prevention aims to prevent the overuse, misuse, and abuse of medical interventions. Immunoglobulins can be used to prevent the development of antibiotic resistance by reducing the use of antibiotics. However, the use of immunoglobulins in preventive healthcare is not without challenges. The cost-effectiveness of immunoglobulin therapy, long-term safety, and the potential for cross-infection are some of the challenges that need to be addressed. Further research is needed to optimize the use of immunoglobulins in preventive health-care delivery. Immunoglobulins are valuable tools in passive immunization for the prevention and treatment of infectious diseases in preventive healthcare. Their use can help reduce the burden of infectious diseases and improve public health outcomes. Keywords: Immunoglobulins, passive immunization, preventive healthcare.

Glycan-specific IgM is critical for human immunity to Staphylococcus aureus

Staphylococcus aureus is a major human pathogen, yet the immune factors that protect against infection remain elusive. High titers of opsonic IgG antibodies, achieved in preclinical animal immunization studies, have consistently failed to provide protection in humans. Here, we investigate antibody responses to the conserved S.aureus surface glycan wall teichoic acid (WTA) and detect the presence of WTA-specific IgM and IgG antibodies in the plasma of healthy individuals. Functionally, WTA-specific IgM outperforms IgG in opsonophagocytic killing of S.aureus and protects against disseminated S.aureus bacteremia through passive immunization. In a clinical setting, patients with S.aureus bacteremia have significantly lower WTA-specific IgM but similar IgG levels compared to healthy controls. Importantly, low WTA-IgM levels correlate with disease mortality and impaired bacterial opsonization. Our findings may guide risk stratification of hospitalized patients and inform future design of antibody-based therapies and vaccines against serious S.aureus infection.

Systematic Review of the Efficacy and Safety of RSV-Specific Monoclonal Antibodies and Antivirals in Development.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection amongst all ages, causing a significant global health burden. Preventative and therapeutic options for RSV infection have long been under development, and recently, several widely-publicised vaccines targeting older adult and maternal populations have become available. Promising monoclonal antibody (mAb) and antiviral (AV) therapies are also progressing in clinical trials, with the prophylactic mAb nirsevimab recently approved for clinical use in infant populations. A systematic review on current progress in this area is lacking. We performed a systematic literature search (PubMed, Embase, Web of Science, ClinicalTrials.gov, EudraCT, ANZCTR-searched Nov 29th, 2023) to identify studies on all RSV-specific mAbs and AV therapies that has undergone human clinical trials since year 2000. Data extraction focused on outcomes related to the therapeutic efficacy and safety of the intervention on trial, and all studies were graded against the OCEBM Levels of Evidence Table. Results from 59 studies were extracted, covering efficacy and safety data on six mAbs (motavizumab, motavizumab-YTE, nirsevimab, ALX-0171, suptavumab, clesrovimab) and 12 AV therapies (ALN-RSV01, RSV604, presatovir, MDT-637, lumicitabine, IFN-α1b, rilematovir, enzaplatovir, AK0529, sisunatovir, PC786, EDP-938). Of the mAbs reviewed, nirsevimab and clesrovimab hold considerable promise. The timeline for RSV-specific AV availability is less advanced, although EDP-938 and AK0529 have reported promising phase 2 efficacy and safety data. Moving forward, passive immunisation and treatment options for RSV infection will play a significant role in reducing the health burden of RSV, complementing recent advancements in vaccine development. TRIAL REGISTRATION: PROSPERO registration: CRD42022376633.