Passive Immunization Research Articles

Possible applications of poultry immunoglobulins focusing on mycotoxin environmental loads and human influence

In addition to their role, immunoglobulins can be used in animal and human diagnostic (immunoassay-based) measurements, prophylaxis and (immuno)therapy. For these purposes, today's "alternative" that is advantageous from an animal ethical point of view is the bird immunoglobulin Y isolated from egg yolk. Its development and production are cost-effective, the complexity is low, and due to its advantageous properties, it can be used in assays or even more so in medical therapies (primarily passive immunization). It is widely used (against pathogens or their toxins) in treatments of intestinal or metabolic diseases and inflammations. Its application in human diagnostics is limited, some markers are measured using immunoglobulin Y as assay component. In this study, a possible application, which is less common today, is presented. The problem of environmental impacts is becoming significant. Due to human activities, industrialization, environmental changes increase the appearance of natural environmental pollutants, including the effects of mycotoxins produced by molds locally and/or globally, which (mainly through nutrition) affect humans. Such agents often appear together, several mycotoxins affect the individual. As a result of their persistence, mycotoxins absorbed in the intestinal tract and accumulated in organs, can already reach levels that can cause physiological and/or behavioral effects. Although the examination of sources (contaminated foods) is regulated by law, the extent of accumulation has not been or cannot be examined and is often insufficiently taken into account. Due to the nature of the technique, the anti-mycotoxin avian immunoglobulin Y could be used both for detection of (deposited) mycotoxin(s) and/or even for immunotherapy (e.g., mycotoxin neutralization). Demonstrating the endocrine-disrupting mycotoxins using the example of zearalenone (with an explanation of its reproductive and immunological effects), we present generation of zearalenone (and mycotoxin-specific) avian immunoglobulin developments, advocate its use in human detection, urging the development of measurements that are suitable for detecting (multiple) accumulation. Orv Hetil. 2023; 164(39): 1527-1536.

Broadly neutralizing antibodies consistently trap HIV-1 in fresh cervicovaginal mucus from select individuals.

In addition to direct neutralization and other classical effector functions, IgG possesses a little recognized and thus under-utilized effector function at mucosal surfaces: Fc-mucin bonds enable IgG to trap viruses in mucus. Due to the paucity of envelope glycoproteins that limits the number of IgG that can bind HIV, it remains poorly understood whether IgG-mucin interactions can effectively immobilize HIV in human cervicovaginal mucus (CVM). Here, we obtained 54 fresh, undiluted CVM specimens from 17 different women, and employed high-resolution multiple particle tracking to quantify the mobility of fluorescent HIV virus-like-particles in CVM treated with various HIV-specific IgG. We observed consistent and effective trapping of HIV by broadly neutralizing antibodies (VRC01, PGT121, and 2F5) in a subset of women. While trapping efficacy was not affected by the menstrual cycle, it was positively correlated with appreciable L. Crispatus populations in the microbiome, and negatively correlated with appreciable L. Iners or G. Vaginalis populations. Our work demonstrates for the first time that IgG-mucin crosslinking is capable of reinforcing the mucosal barrier against HIV, and motivates further investigation of passive immunization against vaginal transmission of STIs. STATEMENT OF SIGNIFICANCE: HIV transmission in women primarily occurs vaginally, yet the 3-way interactions between mucins and HIV virions mediated by HIV-binding antibodies in cervicovaginal mucus (CVM) is not well understood. While IgG-Fc possess weak affinity to mucins that trap virus/IgG complexes in mucus, the effectiveness against HIV remains unclear, due to the low number of virion-bound IgG. Here, we discovered that IgG can trap HIV consistently in CVM from select individuals regardless of their birth control status or menstrual cycle phase. IgG-mediated trapping of HIV was moderately associated with microbiome composition. These results suggest that IgG-mucin interactions could potentially reduce HIV transmission and highlight the importance of mucosal secretions in antibody-mediated prevention of HIV and other sexually transmitted infections.

Evaluation of glutaraldehyde coagulation test and colostrum BRIX refractometer compared with SNAP foal IgG test in neonatal foals.

Prompt diagnosis of passive transfer failure in the neonatal period is important for early treatment. To compare the diagnostic performance of serum glutaraldehyde coagulation test (GCT) and colostrum BRIX% for failure to transfer passive immunity (FTPI) diagnosis with the results of SNAP foal test and to evaluate the results of serum GCT and colostrum BRIX% measurements in foals with diarrhoea in the 0-1 month period. In vitro experiments. Excess serum and colostrum (n: 298) from samples collected from newborn foals and their dams for clinical purposes were used. Foals were classified as FTPI positive (IgG < 8 g/L) or negative (IgG ≥ 8 g/L) using the SNAP foal test. We compared the sensitivity and specificity of serum GCT and colostrum BRIX % for diagnosing FTPI in all foals and in the sub-group of foals which developed diarrhoea within the first month of life was noted. The relationships between the results of the serum GCT and colostrum BRIX% and diarrhoea in foals with and without FTPI were evaluated. Serum GCT and colostrum BRIX % were statistically significantly different (p < 0.05) between the foals without FTPI and with FTPI classified according to the SNAP test. Using a cut-off value for serum GCT of >10, sensitivity was 100% (95% CI 92.9%-100%) and specificity 100% (98.3%-100%) while with a cut-off value of ≤24, with colostrum BRIX% of ≤24 sensitivity was 92% (80.9%-97.8%), and specificity was 98% (95.3-99.3). In the sub-group of foals without FTPI using a colostrum BRIX% cut-off value of ≤26 the sensitivity for prediction of diarrhoea in the 0-1 month period was only 72.4% (52.8-87.3, p < 0.001) with specificity 54.3% (47.6-61.1) but the test performance was not robust (ROC AUC 0.61). The number of repeated measurements in the evaluation of serum GCT, and colostrum BRIX% was low. More clinical problems could be examined. The serum GCT, and colostrum BRIX%, both economical and practical to use in the field, gave results comparable with the SNAP foal IgG test. The ability to accurately predict diarrhoea in the first month of life with these tests was limited.

Применение желточных антител птиц в медико-биологических исследованиях

Passive immunization, proposed by E. Behring, is still a sought-after treatment option using mammalian antibodies. This principle was developed by F. Klemperer in 1893, showing that antibodies that could inactivate the pathogen appeared in the egg yolks of chickens immunized with tetanus toxin. At this time, E. Behring, S. Kitasato, and other investigators studied the inactivating properties of mammalian sera, and an article by F. Klemperer on the transfer of active antibodies from chicken blood to egg yolk remained unattended. Only after the publication of the 3Rs principles by W.M.S. Russell and R.L. Burch in 1959, it was realized that the extraction of egg yolks from immunized birds was fully consistent with the principles of bioethics because the procedure was physiological and non-invasive. Researchers in many countries began to study the yolk immunoglobulins of birds of different species and use them in the diagnosis, therapy and prevention of human and animal diseases. The following species of birds are used for production of IgY-antibodies: chicken, quail, duck, goose, ostrich. Extraction of immunoglobulins from egg yolks of birds is not a difficult task. Many options for the isolation and purification of yolk immunoglobulins from different avian species have been described in the literature. IgY technology has attracted a lot of interest among researchers, especially in the last 10 years. In addition, advances in laboratory techniques and the application of other technologies in the field have resulted in IgY technology becoming more mature for industrial production of specific antibodies and commercialization of the process. Companies are emerging in many countries producing transovarian (yolk) antibodies against pathogens that cause dental caries, peptic ulcer, celiac disease and other diseases. IgY-technologies are a relatively new direction in immunology, based on the passive immunization technology of E. Behring, but it is not sufficiently appreciated in Russia. The replacement of mammalian IgG with avian transovarial IgY allows to develop commercially significant amounts of specific antibodies that do not cause side effects, expands the possibilities of passive immunization methods for the treatment of lesions caused by viruses, bacteria and toxins. This review describes the properties of IgY from different avian species and examples of their application in therapy and disease prevention.

Evaluation of an immunochromatographic point-of-care test for the detection of failure of transfer of passive immunity in calves

BackgroundAs calves are born without circulating immunoglobulin G (IgG) they depend on transfer of passive immunity via colostrum within the first hours of life. If calves are not sufficiently supplied with high qualitative colostrum they suffer from Failure of Transfer of Passive Immunity (FTPI). The objectives of this study were to evaluate a calf-side point-of-care test to detect calves with FTPI and to evaluate the cut-offs for a positive test result. Two hundred fifty calves from 11 dairy farms (born between September 2021 and September 2022) were included, whereof 23 were excluded due to incomplete data. Twelve to 16 h post partum the farmers carried out a point-of-care test (FASTest® IgG bovine, Megacor, Austria) using a whole blood sample. Between the 3rd and the 6th day of age, all calves were physically examined and blood samples were collected to carry out further point-of-care tests using whole blood supernatant and plasma and for measuring the Brix values in serum and plasma. Brix values in serum were used as reference for the evaluation of the point-of-care test between the 3rd and the 6th day of age, as radial immunodiffusion assays could not be conducted simultaneously.ResultsBrix values were not normally distributed (median at 8.6% and 9.3% in serum and plasma). In this study, the cut-off values for the point-of-care tests using whole blood supernatant and plasma were at 8.3% Brix in serum. FASTest® IgG bovine shows high sensitivities of 90% and 84% and specificities of 70% and 72% for whole blood supernatant and plasma.ConclusionsOf the 227 investigated calves, 39.7% showed Brix values of < 8.4% (cut-off for FTPI) which indicates an urgent need to improve colostrum management. The results of the study suggest that the FASTest® IgG bovine is a suitable on-farm method to assess FTPI in whole blood supernatant and plasma of calves between the 3rd and the 6th day of age. However, the results also show that FASTest® IgG bovine is not adequate to test for FTPI using whole blood at 12 to 16 h post partum.

A Bioreactor-Based Yellow Fever Virus-like Particle Production Process with Integrated Process Analytical Technology Based on Transient Transfection.

Yellow Fever (YF) is a severe disease that, while preventable through vaccination, lacks rapid intervention options for those already infected. There is an urgent need for passive immunization techniques using YF-virus-like particles (YF-VLPs). To address this, we successfully established a bioreactor-based production process for YF-VLPs, leveraging transient transfection and integrating Process Analytical Technology. A cornerstone of this approach was the optimization of plasmid DNA (pDNA) production to a yield of 11 mg/L using design of experiments. Glucose, NaCl, yeast extract, and a phosphate buffer showed significant influence on specific pDNA yield. The preliminary work for VLP-production in bioreactor showed adjustments to the HEK cell density, the polyplex formation duration, and medium exchanges effectively elevated transfection efficiencies. The additive Pluronic F-68 was neutral in its effects, and anti-clumping agents (ACA) adversely affected the transfection process. Finally, we established the stirred-tank bioreactor process with integrated dielectric spectroscopy, which gave real-time insight in relevant process steps, e.g., cell growth, polyplex uptake, and harvest time. We confirmed the presence and integrity of YF-VLP via Western blot, imaging flow cytometry measurement, and transmission electron microscopy. The YF-VLP production process can serve as a platform to produce VLPs as passive immunizing agents against other neglected tropical diseases.

Passive immunization with anti-FimA egg yolk antibodies (IgYs) mitigate Acinetobacter baumannii pneumonia in mice

Acinetobacter baumannii is a formidable pathogen, characterized by high mortality rates and pan-drug-resistant strains. Current commercial antibiotics lack efficacy against drug-resistant variants, necessitating the search for alternative treatments. This study investigates the potential of egg yolk immunoglobulin (IgY) as a cost-effective biomolecule for passive protection against A. baumannii pneumonia. FimA (ABAYE2132), a key virulence factor involved in biofilm development and lung cell adherence, emerges as a promising antigen for triggering protective IgY production. Recombinant FimA was expressed, purified, and used for intramuscular immunization of laying White Leghorn hens. IgY antibodies were subsequently extracted from egg yolks, with their reactivity assessed through indirect ELISA. Neutropenic mice received intranasal administration of IgYs one hour prior to the challenge with a clinical A. baumannii isolate (10 ×LD50). The specific anti-FimA IgYs detected recombinant FimA and provided 100% protection against bacterial infection, while non-specific IgYs prolonged survival for up to 72 h. In contrast, control mice succumbed to infection within 24 h. Analysis of bacterial loads in lungs and spleens after 16 h reveals the following order: control > non-specific IgY > anti-FimA IgY. These findings highlight FimA as a suitable antigen for the development of protective IgYs against A. baumannii.

Absence of blood donors’ anti-SARS-CoV-2 antibodies in pre-storage leukoreduced red blood cell units indicates no role of passive immunity for blood recipients

Transfer of vaccine antibodies (Ab) from donors to recipients after transfusion of packed red blood cells (RBC) is supposed, thus affecting the recipients’ response to vaccinations. In this prospective study, SARS-CoV-2 IgG level in donors’ serum and RBC supernatant samples was assessed. Among 346 subjects, 280 were referred for hyperimmune plasma donation and 30 for whole blood donations. All units underwent pre-storage filtration, and residual plasma volume was 18±18 mL. The mean total IgG and IgM levels were 171.43 ± 48.79 and 11.43 ± 10.69 mg/dL respectively, with significant reduction after plasma depletion and filtration (IgG 5.86 ± 5.2 and IgM 1.43 ± 3.78, p < 0.05). Anti-COVID-19 Ab were identified in serum of 28/30 (93.5%) blood donors but were absent in all blood units. The mean value of anti-SARS-CoV-2 IgG level in donors’ serum samples and in RBC units was 8.80 S/C (range 0.01–23.4) and 0.11 (range 0.01–0.37) S/C, respectively (p<0.05). This study shows deplasmation and leukodepletion of RBC units ensured removal of IgG content and no red blood cell unit was reactive for anti-COVID-19 antibodies even from donors with high serum titre. These findings demonstrate that deplasmated and leukodepleted RBCs are not to be considered blood products containing substantial amounts of immune globulin, and differently from other blood derived-products containing Ab, transfusions with deplasmated and leukodepleted RBCs do not require delayed vaccinations and a revision of current recommendations is requested.

Investigation of brix refractometry for estimating bovine colostrum immunoglobulin G concentration.

Many dairy operations uses a Brix refractometer to assess the quality of first-milking colostrum. This study investigated whether a digital Brix refractometer could be used in a model to predict colostrum IgG concentration and whether more than one %Brix threshold could be used for different colostrum IgG concentrations. Colostrum from 182 animals was tested using a digital Brix refractometer and by single radial immunodiffusion. Statistical analysis, using simple linear regression to relate %Brix results with corresponding colostral IgG concentration, and receiver operating characteristic (ROC) analysis were used to identify %Brix cutoffs that had no false positive results. Colostral IgG concentrations from digital Brix refractometry had a R2 value of 0.818 and a S-value of 21.7 g/L. The large S-value shows that a digital Brix refractometer should not be used in a model to predict colostrum IgG concentration. However, %Brix scores of 19.0, 22.0, 25.0 and 30.0 percent can be used to estimate minimum colostral IgG concentrations of 25, 50, 75 and 100 g/L. These four cutoffs can be used to strategically feed smaller volumes of colostrum to newborn calves. Smaller volumes may reduce unwanted side effects and shorten the time interval in which calves refuse to nurse, while still delivering an adequate mass of IgG to have successful transfer of passive immunity.

Evaluation of the differences in proteomics of high-quality bovine colostrum and low-quality bovine colostrum.

Although there are studies on colostrum and milk proteomics of different species in the literature, there is no published report about different quality bovine colostrums' proteomics. The aim of this study was to compare the proteome content of high- and low-quality bovine colostrums for the first time. Colostrum samples were collected from 32 Holstein cows from the same farm that had just calved. Brix% levels of colostrums were measured, and then, those with a Brix% value of ≥27% were classified as high-quality and those with a Brix% value of <22% as low-quality. Three samples from high-quality and low-quality colostrums were selected and proteomic analyses were performed by pooling separately. Totally 95 proteins were identified in the colostrums, and 19 of them showed significant changes between high- and low-quality colostrums. Expressions in colostrum of glycosylation-dependent cell adhesion molecule-1, cofilin-1, alpha-S2-casein, alpha-lactalbumin, alpha-1B-glycoprotein, actin_cytoplasmic-1, nucleobindin-1, cathelicidin-4, inter-alpha-trypsin inhibitor heavy chain H4, chitinase-3-like protein 1 and monocyte differentiation antigen CD14 were lower, whereas tetranectin, secreted frizzled-related protein-1 (SFRP1), perilipin-2, coatomer subunit epsilon (COPE), butyrophilin subfamily 1 member A1, polyubiquitin-B, lactadherin and albumin levels were higher in high-quality colostrum than low-quality colostrum. Moreover, SFRP1, COPE and cathelicidin-4 proteins were identified for the first time in bovine colostrum. In high-quality colostrum, the most prominently down-regulated proteins were cathelicidin-4 (26.01-fold) and cofilin-1 (17.42-fold), and the most prominently up-regulated proteins were COPE (3.37-fold) and tetranectin (3.07-fold). It was detected that the proteome contents of high- and low-quality bovine colostrums were different from each other. As new functions are added to the protein databases regarding these proteins detected in colostrums, the interactions of proteins with each other and with other molecules will be detailed and the effects of high-quality colostrums on passive transfer immunity and calf health will be understood in full detail.

The effect of maternal supply of rumen-protected protein to Holstein Friesian cows during the dry period on the transfer of passive immunity and colostral microbial composition

The objective of this study was to analyze if maternal supply of rumen-protected protein during the dry period can affect the IgG concentration and microbial composition of colostrum and the IgG absorption and fecal microbial composition in the calf. Seventy-four multiparous Holstein Friesian (HF) dairy cows were stratified per parity and randomly assigned to one of 2 different dry period diets, a diet with a low crude protein (CP) level (LP) and a diet with a high CP level (HP) by addition of rumen-undegraded protein (RUP; formaldehyde-treated soybean meal, Mervobest, Nuscience, Drongen, Belgium). Colostrum was collected within 1 h after calving and IgG concentration was quantified by radial immunodiffusion analysis. Forty-nine calves (23 female and 26 male) were enrolled in the trial with a 2 × 2 factorial design, with prenatal and postnatal treatment as the 2 independent variables. This led to 4 experimental groups: LPLP, LPHP, HPLP, and HPHP, in which the first 2 letters refer to the prenatal treatment (diet of the dam) and the last 2 refer to the postnatal treatment (diet of the colostrum-producing cow). Calves received 3× 2 L of colostrum within 2, 6, and 24 h after birth. Meconium and feces were collected solely from female calves (n = 18) by digital palpation of the rectum, immediately after birth and before colostrum administration and at d 3 of age. Microbial DNA was extracted from meconium (n = 9), feces (n = 15), and colostrum (n = 49). Amplicon sequencing of the bacterial V3-V4 region of the 16S rRNA gene was performed for characterization of the bacterial communities. Colostrum IgG concentration was higher in cows that were supplemented with RUP, especially in cows entering their second lactation (LSM ± SEM 61.3 ± 2.3 vs. 55.2 ± 2.8 g of IgG/L). Calves born out of LP cows that received colostrum from HP cows (LPHP) had a lower serum IgG level compared with HPHP and LPLP calves (LSM ± SEM 14.2 ± 1.3 vs. 18.8 ± 1.2 and 20.9 ± 1.3 g of IgG/L in HPHP and LPLP, respectively). The most abundant phyla in colostrum were Proteobacteria (48.2%), Firmicutes (24.8%), Bacteroidetes (9.5%), and Actinobacteria (5.0%). The most abundant phyla in calf meconium and feces were Firmicutes (42.5 and 47.5%), Proteobacteria (21.7% and 33.7%), Bacteroidetes (16.8% and 15.7%), and Actinobacteria (2.9% and 3.1%). There was no difference in the overall microbial communities between colostrum from HP and LP cows. However, 2 genera (both members of the family Lachnospiraceae) were more abundant in colostrum from HP cows compared with LP cows. The microbial composition of meconium, feces and colostrum differed from each other. Fecal samples were more similar to each other and are characterized by a lower intersample diversity compared with colostrum and meconium samples. To conclude, increasing the CP level by addition of RUP in the dry period diet affected the colostrum IgG concentration and the transfer of passive immunity, but did not change the overall microbial composition of colostrum nor of meconium and feces in the calf.

Anticipating HIV viral escape - resistance to active and passive immunization.

Active and passive immunization strategies are challenged by the extraordinary diversity of HIV, and the need for high titers of neutralizing antibodies to confer protective immunity. This review summarises recent studies and the barrier that these interventions will need to overcome to prevent viral resistance. Studies from the antibody mediated prevention trial identified a measure of protective titers, finding that higher titers than anticipated will be needed to prevent infection. This benchmark has advanced our ability to predict combinations of broadly neutralizing antibodies (bNAbs) that will provide optimal coverage. To limit escape, these combinations should ensure that the majority of viruses are bound by a minimum of two antibodies. The characterization of currently circulating viruses has revealed increased resistance to some bNAbs over time, highlighting the need for continued surveillance, especially in under-studied populations and subtypes. Active vaccination will face similar challenges in combating diversity, although despite successes in germline targeting, this approach is not yet able to elicit bNAbs. Cumulatively these studies highlight the need to target multiple antibody epitopes for maximum coverage, but also to restrict escape pathways. Successful immunization strategies should anticipate viral escape and devise strategies to counteract this.

Commercialization of Colostrum Milk for the Benefit of Human Health in Gunupur City, Odisha

Colostrum milk is the first milk produce after the parturition or the baby birth. It is a necessary food for a new born baby for increase its immune system to protect against pathogen and boost the physiological performance, growth and mental development. Colostrum milk contains polysaturated fatty acids, growth factor, hormones, oligosaccharide, lactoferrin, a greater number of leukocytes (WBC cells) and high concentration of immunoglobulins. Colostrum milk provides passive immunity to the new born. People in the Gunupur block are establishing dairy farms and producing milk on a large scale. So, if we establish a factory of Colostrum milk then, we can easily collect the colostrum milk from the dairymen and supply the products by suitable transport medium to other states of India. The colostrum milk is highly proteinaceous product which is highly beneficial to the patients and build a new born babies’ immune system. My goal is to use government funding to commercialize colostrum milk in the Gunupur block and distribute it to nearby government hospitals and underprivileged citizens.

Association Between Low Anti-spike Antibody Levels After the Third Dose of SARS-CoV-2 Vaccination and Hospitalization due to Symptomatic Breakthrough Infection in Kidney Transplant Recipients.

Whether anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels post-third coronavirus disease (COVID-19) vaccination correlate with worse outcomes due to breakthrough infection is unclear. We evaluated the association between anti-SARS-CoV-2 antibody levels and symptomatic breakthrough infection or hospitalization during the Omicron surge in kidney transplant recipients. In total, 287 kidney transplant recipients expected to receive a third vaccination were enrolled between November 2021 and February 2022. The Abbott SARS-CoV-2 IgG II Quant test (Abbott, Chicago, IL, USA) was performed within three weeks before and four weeks after the third vaccination. The incidence of symptomatic breakthrough infection and hospitalization from two weeks to four months post-third vaccination was recorded. After the third vaccination, the seropositive rate and median antibody titer of the 287 patients increased from 57.1% to 82.2% and from 71.7 (interquartile range [IQR] 7.2-402.8) to 1,612.1 (IQR 153.9-5,489.1) AU/mL, respectively. Sixty-four (22.3%) patients had symptomatic breakthrough infections, of whom 12 required hospitalization. Lower anti-receptor-binding domain (RBD) IgG levels (<400 AU/mL) post-third vaccination were a risk factor for symptomatic breakthrough infection (hazard ratio [HR]=3.46, P<0.001). Anti-RBD IgG levels <200 AU/mL were a critical risk factor for hospitalization (HR=36.4, P=0.007). Low anti-spike IgG levels after third vaccination in kidney transplant recipients were associated with symptomatic breakthrough infection and, particularly, with hospitalization during the Omicron surge. These data can be used to identify patients requiring additional protective measures, such as passive immunization using monoclonal antibodies.

Vertical transmission and maternal passive immunity post-SARS-CoV-2.

Since 2020, the highly contagious nature and various transmission routes of SARS-CoV-2 have rendered the pandemic interminable. Vertical transmission (VT) through the placenta and breast milk, which is frequent for certain virus types, is thought to exist for SARS-CoV-2 and is hypothesized by many researchers. Conversely, antibodies are produced to counteract the effect of viruses. Since newborns' immunologic system cannot produce proper antibodies, maternal antibodies are usually transferred from mother to infant/fetus to meet the need. This theory leads to the hypothesis of transmission of antibodies through the placenta and breast milk following SARS-CoV-2 infection or vaccination. This paper further discusses these hypotheses, considering consequences of fetus/infant harm versus benefit.

Cancer Immunotherapy Using Bioengineered Micro/Nano Structured Hydrogels.

Hydrogels, a class of materials with a 3Dnetwork structure, are widely used in various applications of therapeutic delivery, particularly cancer therapy. Micro and nanogels as miniaturized structures of the bioengineered hydrogels may provide extensive benefits over the common hydrogels in encapsulation and controlled release of small molecular drugs, macromolecular therapeutics, and even cells. Cancer immunotherapy is rapidly developing, and micro/nanostructured hydrogels have gained wide attention regarding their engineered payload release properties that enhance systemic anticancer immunity. Additionally, they are a great candidate due to their local administration properties with a focus on local immune cell manipulation in favor of active and passive immunotherapies. Although applied locally, such micro/nanostructured can also activate systemic antitumor immune responses by releasing nanovaccines safely and effectively inhibiting tumor metastasis and recurrence. However, such hydrogels are mostly used as locally administered carriers to stimulate the immune cells by releasing tumor lysate, drugs, or nanovaccines. In this review, the latest developments in cancer immunotherapy are summarized using micro/nanostructured hydrogels with a particular emphasis on their function depending on the administration route. Moreover, the potential for clinical translation of these hydrogel-based cancer immunotherapies is also discussed.

Review of the Safety, Efficacy and Tolerability of Palivizumab in the Prevention of Severe Respiratory Syncytial Virus (RSV) Disease.

Respiratory Syncytial Virus (RSV) is a major global cause of childhood morbidity and mortality. Palivizumab, a monoclonal antibody that provides passive immunity against RSV, is currently licensed for prophylactic use in specific "high-risk" populations, including congenital heart disease, bronchopulmonary dysplasia and prematurity. Available research suggests palivizumab use in these high-risk populations can lead to a reduction in RSV-related hospitalization. However, palivizumab has not been demonstrated to reduce mortality, adverse events or length of hospital stay related to RSV. In this article, we review the management of RSV, indications for palivizumab prophylaxis, the safety, cost-effectiveness and efficacy of this preventative medication, and emerging therapeutics that could revolutionize future prevention of this significant pathogen.

Comparison of Anti-Trop2 Extracellular Domain Antibodies Generated Against Peptide and Protein Immunogens for Targeting Trop2-Positive Tumour Cells.

Trophoblast antigen 2 (Trop2) is a transmembrane glycoprotein upregulated in multiple solid tumours. Trop2-based passive immunotherapies are in clinical trials, while Trop2 targeting CAR-T cell-based therapies are also reported. Information about its T- and B-cell epitopes is needed for it to be pursued as an active immunotherapeutic target. This study focused on identification of immunodominant epitopes in the Trop2 extracellular domain (ECD) that can mount an efficient anti-Trop2 antibody response. In silico analysis using various B-cell epitope prediction tools was carried out to identify linear and conformational B-cell epitopes in the ECD of Trop2. Three linear peptide immunogens were shortlisted and synthesized. Along with linear peptides, truncated Trop2 ECD that possesses combination of linear and conformational epitopes was also selected. Recombinant protein immunogen was produced in 293-F suspension culture system and affinity purified. Antisera against different immunogens were characterized by ELISA and Western blotting. Two anti-peptide antisera detected recombinant and ectopically expressed Trop2 protein; however, they were unable to recognize the endogenous Trop2 protein expressed by cancer cells. Antibodies against truncated Trop2 ECD could bind to the endogenous Trop2 expressed on the surface of cancer cells. In addition to their high avidity, these polyclonal anti-sera against truncated Trop2 protein also mediated antibody-dependent cell-mediated cytotoxicity (ADCC). In summary, our comparative analysis demonstrated the utility of truncated Trop2 ECD as a promising candidate to be pursued as an active immunotherapeutic molecule against Trop2-positive cancer cells.

Defining optimal thresholds for digital Brix refractometry to determine IgG concentration in ewe colostrum and lamb serum in Scottish lowland sheep flocks.

This research aimed to define thresholds for ewe colostrum and lamb serum Brix refractometer measurements in lowland Scottish sheep. This would facilitate the use of this convenient, sheep-side test, enabling quick and accurate identification of poor quality colostrum and prevention of failure of transfer of passive immunity (FTPI) in lambs. Secondary aims were to identify risk factors for poor colostrum quality and FTPI in lambs. Serum samples (n=233) were collected from lambs between 24 and 48hrs after birth, from four lowland Scottish meat sheep farms. Pre-suckle colostrum samples (n=112) were also collected from ewes on two of these farms. Farmers provided information on litter size, ewe body condition score, ewe breed and dystocia. Duplicate digital Brix refractometer measurements were compared with immunoglobulin G (IgG) radial immunodiffusion (RID) testing for all colostrum and serum samples. Receiver operating characteristic (ROC) curves were used to redefine thresholds for Brix testing in colostrum and serum. Linear regression models were constructed with colostrum and serum IgG concentration as the outcomes of interest. Colostrum and serum IgG concentrations were highly variable. The prevalence of inadequate colostrum quality (using <50g/L IgG on RID) was 4.5% (95% CI = 1.5 - 10.1) and the prevalence of FTPI (using <15g/L IgG in serum on RID) was 7.73% (95% CI = 4.64-11.93). A ewe's colostrum IgG concentration was significantly and positively associated with the serum IgG concentration of her lamb(s) (p=0.02). ROC analysis defined a Brix threshold for adequate colostrum quality of >22.10% (sensitivity 80% (95%CI=28.4-99.5), specificity 90% (95%CI=82.3-94.8)). ROC analysis defined a Brix threshold for serum of >8.65% for adequate passive transfer of immunity in Scottish lambs (sensitivity 94% (95%CI=72.7-99.8), specificity 82% (95%CI=76.6-87.2)). To optimise passive transfer of immunity in lambs, we suggest that ewe colostrum Brix measurements be defined as 'poor' (<22%); 'fair' (22-26%) and 'good' (>26%); and lamb serum as 'poor' (<8%); 'fair' (8-9%) and 'good' (>9%). It is recommended that these tests are used as for flock screening, using samples from multiple animals.

A male Covid-19 convalescent plasma donor with long existence of SARS-Cov-2 antibodies: a case report

Covid-19 Convalescent Plasma (CCP) was one of alternative therapy for Covid-19 patients. The use of convalescent plasma as an adjunct therapy must consider its efficacy, benefits, and risk, both for the patient and the donor. Convalescent Plasma was produced from purified human plasma. Convalescent Plasma was a passive immunity which provide active antibodies. CCP give immunity to the patient through the transfusion of a survivor’s antibodies. We were reporting a case of male CCP donor with long existence of SARS-Cov-2. This donor performed up to 16 donations, which was an unusual case in CCP donor. The SARS-CoV-2 antibody titer was analyzed using Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics). The SARS-CoV-2 antibody showed high level of total SARS-CoV-2 antibodies, with the Cut off Indexes (COI) anti SARS-Cov-2 antibody were still quite high (132 U/mL). The highest donor antibody COI (204.6 U/mL) was seen in 11th donation at 6 months after recovery, while the lowest antibody COI (130.8 U/mL) was in 15th donation at 7 months after recovering. Evaluation of donor health status were performed after the 16th donation and analyzed as well. In conclusion, 16 CCP donations of 600 mL resulting in 48 units of 200 mL plasma in 8 months was safe for the donor, with the SARS-Cov-2 antibody titer remained high in the whole period.