Concentration and heritability of immunoglobulin G and natural antibody immunoglobulin M in dairy and beef colostrum along with serum total protein in their calves

Immunoglobulin (Ig) G and natural antibody (NAb) IgM are passively transferred to the neonatal calf through bovine colostrum. Maternal IgG provides pathogen- or vaccine-specific protection and comprises about 85 percent of colostral Ig. Natural antibody IgM is less abundant but provides broad and non-specific reactivity, potentially contributing to protection against the dissemination of pathogens in the blood (septicemia) in a calf’s first days of life. In the dairy and beef industries, failure of passive transfer (FPT) of colostral Ig (serum total protein (STP) <5.2 g/dL) is still a common concern. The objectives of this study were to, i) compare colostral IgG concentrations and NAb-IgM titers between dairy and beef cows; ii) assess the effect of beef breed on colostral IgG; iii) compare passive transfer of colostral Ig in dairy and beef calves; and iv) estimate the heritability of colostral IgG and NAb-IgM. Colostrum was collected from Holstein dairy (n=282) and crossbred beef (n=168) cows at the University of Guelph dairy and beef research centres. Colostral IgG was quantified by radial immunodiffusion and NAb-IgM was quantified by an enzyme-linked immunosorbent assay. In dairy (n=308) and beef (n=169) calves, STP was estimated by digital refractometry. Beef cows had significantly greater colostral IgG (146.5 ± 9.5 SEM g/L) than dairy cows (92.4 ± 5.2 g/L, p <0.01). Beef cows with a higher proportion of Angus ancestry had significantly lower colostral IgG (125.5 ± 5.8 g/L) than cows grouped as “Other” (142.5 ± 4.9 g/L, p= 0.02). Using the FPT cut-off, 13% of dairy and 16% of beef calves had FPT; still, beef calves had a significantly larger proportion with excellent passive transfer (STP ≥6.2 g/dL, p <0.01). The heritability of colostral IgG was 0.04 (± 0.14) in dairy and 0.14 (± 0.32) in beef. Colostral NAb-IgM titers in dairy (12.12 ± 0.22, log2 (reciprocal of titer)) and beef cows (12.03 ± 0.19) did not differ significantly (p=0.71). The range of NAb-IgM titers was 9.18 to 14.60, equivalent to a 42-fold range in antibody concentration. The heritability of colostral NAb was 0.24 (± 0.16) in dairy and 0.11 (± 0.19) in beef cows. This study is the first to compare colostral NAb-IgM between dairy and beef cows. Based on the range in NAb-IgM titers and the heritability, selective breeding may improve colostrum quality and protection for neonatal calves in the early days of life.

Supplementing Mannan Oligosaccharide Reduces the Passive Transfer of Immunoglobulin G and Improves Antioxidative Capacity, Immunity, and Intestinal Microbiota in Neonatal Goats

Successful establishment of passive immunity (PIT) and regulation of intestinal microbiota are crucial for ruminants to maintain body health and reduce the risk of disease during the neonatal period. Thus, the objective of this study was to investigate the effects of mannan oligosaccharide (MOS) supplementation on passive transfer of immunoglobulin G (IgG), serum inflammatory cytokines and antioxidant levels as well as bacteria composition in the ileal digesta. A total of 14 healthy neonatal Ganxi black goats with similar birth weight (BW: 2.35 ± 0.55 kg) were selected and allocated into two groups, only fed colostrum and milk replacer (CON, n = 7) and supplemented MOS (0.06% of birth BW) in the colostrum and milk replacer (MOS, n = 7). The results indicated that MOS supplementation significantly reduced (p < 0.05) serum IgG level at 3 and 6 h after colostrum feeding. Serum GLP-1 level of goats in the MOS group was significantly lower (p = 0.001) than that in the CON group. Goats in the MOS group had higher serum CAT and lower MDA level than those in the CON group (p < 0.05). Serum anti-inflammatory cytokine level of interleukin 4 (IL-4) was increased (p < 0.05), while pro-inflammatory cytokine IL-6 level was reduced (p < 0.05) in the MOS group when compared with the CON group. In addition, MOS supplementation remarkably increased (p < 0.05) the level of secretory IgA (sIgA) in the ileal digesta. Principal coordinate analysis of 16S rRNA sequence based on Brinary jaccard, Bray curtis, and weighted UniFrac distance of ileal microbiota showed a distinct microbial differentiation between the CON and MOS groups (p < 0.05). The relative abundance of Firmicutes in the MOS group was higher than that in the CON group, while the abundance of Verrucomicrobia was lower in the MOS group than that in the CON group at the phylum level (p < 0.05). The relative abundance of Proteobacteria tended to decrease (p = 0.078) in the MOS group at the phylum level. The results of LEfSe analysis showed that MOS group was characterized by a higher relative abundance of Lactobacillus, while the CON group was represented by a higher relative abundance of Akkermansia and Ruminiclostridium_5. Our findings demonstrated that MOS supplementation during the neonatal period increases antioxidant capacity and reduces the inflammatory response, and promotes IgA secretion and Lactobacillus colonization in the ileum. Thus, MOS induced positive effects are more pronounced in neonatal goats that might be an effective approach to maintain intestinal health and improve the surviving rate of neonatal ruminants.

Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus

SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated low dose intraveneous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.

Protective effects of combining monoclonal antibodies and vaccines against the Plasmodium falciparum circumsporozoite protein

Combinations of monoclonal antibodies (mAbs) against different epitopes on the same antigen synergistically neutralize many viruses. However, there are limited studies assessing whether combining human mAbs against distinct regions of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) enhances in vivo protection against malaria compared to each mAb alone or whether passive transfer of PfCSP mAbs would improve protection following vaccination against PfCSP. Here, we isolated a panel of human mAbs against the subdominant C-terminal domain of PfCSP (C-CSP) from a volunteer immunized with radiation-attenuated Pf sporozoites. These C-CSP-specific mAbs had limited binding to sporozoites in vitro that was increased by combination with neutralizing human “repeat” mAbs against the NPDP/NVDP/NANP tetrapeptides in the central repeat region of PfCSP. Nevertheless, passive transfer of repeat- and C-CSP-specific mAb combinations did not provide enhanced protection against in vivo sporozoite challenge compared to repeat mAbs alone. Furthermore, combining potent repeat-specific mAbs (CIS43, L9, and 317) that respectively target the three tetrapeptides (NPDP/NVDP/NANP) did not provide additional protection against in vivo sporozoite challenge. However, administration of either CIS43, L9, or 317 (but not C-CSP-specific mAbs) to mice that had been immunized with R21, a PfCSP-based virus-like particle vaccine that induces polyclonal antibodies against the repeat region and C-CSP, provided enhanced protection against sporozoite challenge when compared to vaccine or mAbs alone. Collectively, this study shows that while combining mAbs against the repeat and C-terminal regions of PfCSP provide no additional protection in vivo, repeat mAbs do provide increased protection when combined with vaccine-induced polyclonal antibodies. These data should inform the implementation of PfCSP human mAbs alone or following vaccination to prevent malaria infection.

A mosquito AgTRIO monoclonal antibody reduces early Plasmodium infection of mice

Malaria begins when an infected mosquito injects saliva containing Plasmodium sporozoites into the skin of a vertebrate host. Passive immunization of mice with mosquito AgTRIO antisera offers significant protection against Plasmodium infection of mice. Furthermore, passive transfer of both AgTRIO antisera and an anti-circumsporozoite protein monoclonal antibody provides synergistic protection. In this study, we generated monoclonal antibodies against AgTRIO to delineate the regions of AgTRIO associated with protective immunity. Monoclonal antibody 13F-1 markedly reduced Plasmodium infection in mice and recognized a region, VDDLMAKFN, in the carboxyl terminus of AgTRIO. 13F-1 is an IgG2a isotype monoclonal antibody and the Fc region is required for protection. These data will aid in the generation of future malaria vaccines that may include both pathogen and vector antigens.

To bnAb or Not to bnAb: Defining Broadly Neutralising Antibodies Against HIV-1

Since their discovery, antibodies capable of broad neutralisation have been at the forefront of HIV-1 research and are of particular interest due to in vivo passive transfer studies demonstrating their potential to provide protection. Currently an exact definition of what is required for a monoclonal antibody to be classed as a broadly neutralising antibody (bnAb) has not yet been established. This has led to hundreds of antibodies with varying neutralisation breadth being studied and has given insight into antibody maturation pathways and epitopes targeted. However, even with this knowledge, immunisation studies and vaccination trials to date have had limited success in eliciting antibodies with neutralisation breadth. For this reason there is a growing need to identify factors specifically associated with bnAb development, yet to do this a set of criteria is necessary to distinguish bnAbs from non-bnAbs. This review aims to define what it means to be a HIV-1 bnAb by comparing neutralisation breadth, genetic features and epitopes of bnAbs, and in the process highlights the challenges of comparing the array of antibodies that have been isolated over the years.

A live yeast supplementation to gestating ewes improves bioactive molecules composition in colostrum with no impact on its bacterial composition and beneficially affects immune status of the offspring

Colostrum quality is of paramount importance in the management of optimal ruminant growth and infectious disease prevention in early life. Live yeast supplementation effect during the last month of gestation was evaluated on ewes colostrum composition. Two groups of ewes (n=14) carrying twin lambs were constituted and twins were separated into groups (mothered or artificially-fed) 12h after birth. Nutrient, oligosaccharides (OS), IgG and lactoferrin concentrations were measured over 72h after lambing, and bacterial community was described in colostrum collected at parturition (T0). Immune passive transfer was evaluated through IgG measurement in lamb serum. In both groups, colostral nutrient, OS concentrations and IgG concentrations in colostrum and lamb serum decreased over time, (p < 0.01) except for lactose, which slightly increased (p < 0.001) and lactoferrin which remained stable. Bacterial population was stable over time with high relative abundances of Aerococcaceae, Corynebacteriaceae, Moraxellaceae and Staphylococcaceae in T0-colostrum. No effect of supplementation was observed in nutrient and lactoferrin concentrations. In supplemented ewes, colostral IgG level was higher at T0 and a higher level of serum IgG was observed in lambs born from supplemented mothers and artificially-fed, while no effect of supplementation was observed in the mothered lambs groups. Using a metabolomic approach, we showed that supplementation affected OS composition with significantly higher levels of colostral Neu-5Gc compounds up to 5h after birth. No effect of supplementation was observed on bacterial composition. Our data suggest that live yeast supplementation offsets the negative impact of early separation and incomplete colostrum feeding in neonate lambs.

Evaluation of materno-fetal antibody transfer in patients with antiphospholipid syndrome

Introduction: Antiphospholipid syndrome (APS) is characterized by thrombotic events and recurrent pregnancy losses and is considered the most common acquired thrombophilia.Objective: To carry out a narrative review of the transplacental passage and antibodies in patients with APS.Methods: A narrative literature review.Results: When it is not associated with any connective tissue disease, it is said to be primary, and when in association with systemic lupus erythematosus, it is said to be secondary. Gestational morbidity is frequent, and it is crucial to evaluate the passage of these antibodies transplacentally since there are animal models of the syndrome with passive transfer of these antibodies. The transplacental passage of specific antibodies has already been determined in studies, which demonstrated low levels of these antibodies in the maternal serum, but an efficient transplacental passage for the newborn.Conclusions: There are few studies on this maternal-infant passage in patients with APS reviewed here.

280 Descriptive Characteristics of Preweaned Heifer Raising Practices on China Dairy Farms: Colostrum Quality, Passive Transfer Status and Growth Performance

Few data are available on the descriptive characteristics of colostrum quality, passive transfer status and growth performance within a national population in China. This study included 110 dairy operations in 23 provinces, and data were obtained from management software, report system and questionnaires from 2015 to 2019. Data were analyzed using SAS (version 9.0, SAS Institute Inc., Cary, NC, USA). The results showed that colostrum quality was measured in 96.4% of farms and colostrum was pasteurized in 91.8% of farms. 83.6% of colostrum was excellent (Brix &gt; 22%). Colostrum could be fed to calves within 1 hour after birth in 86.4% of farms. Besides, calves that experienced failure of passive transfer (serum total protein &lt; 5.2 g/dl) decreased from 2015 to 2019 and accounted for 0.75% of calves in 2019. Most farms (48.8%) feed 400 kg - 600 kg milk during the preweaning period and whole milk was the main type of liquid diet accounting for 70.6% of farms. Meanwhile, 22.0% of farms chose to feed forage before weaning, and 90.1% of these farms fed oat hay. The average birth weight of calves was 37.8 kg and the average daily gain of preweaning calves was 848.3 g/d. For preweaning calves, the proportion of single housing was more than 60%, whereas postweaning calves were mainly raised in groups. The morbidity of preweaning calves in China decreased annually, from 43.3% in 2015 to 25.4% in 2019. Digestive diseases and respiratory diseases were two main diseases, and accounted for 46.0% and 38.4%, respectively. This study provides an overview on dairy calves raising practices in China.

PSIII-13 The Effect of the inclusion of liquid brewers yeast during gestation on colostrum quality and passive transfer of immunity in lambs

Fourteen Suffolk/Suffolk x Hampshire pregnant ewes were utilized to evaluate the effects of liquid brewers yeast on colostrum quality and the transfer of passive immunity in their offspring. Parainfluenza type 3 (PI3) vaccination was used elicit an immune response. Ewes were vaccinated with PI3 at 33 and 18 d prior to expected lambing day. Ewes were randomly assigned to one of two treatments: late gestation diet (CON) or late gestation diet supplemented with liquid brewers yeast at an average rate of 60 g DM/d (LBY). Ewes were fed treatment diets from 45 d prior to expected lambing to 3 d post lambing. Blood was collected from ewes’ via jugular venipuncture prior to vaccination and within 6 hours postpartum. Blood was collected also from the jugular vein of lambs (n = 22) at 3 d of age. Ewe and lamb blood serum was tested for Bovine Parainfluenza 3 Virus and data on anti-PI3 antibody titers was evaluated. Colostrum was collected within 4 hours postpartum and analyzed for colostral IgG concentrations using a refractometer in % Brix. A PROC GLM model was performed in SAS 9.4, where the model for ewe colostrum quality and lamb anti-PI3 titers analyses included the main effect of treatment diet. All vaccinated ewes were positive for PI3 antibodies (&gt;64 titer) immediately prior to and post lambing. All lambs tested positive for antibody titers for PI3 with no differences between treatment (197.3 for CON and 160.8 for LBY; P = 0.43). The colostral IgG concentrations did not differ between CON (30.4% Brix) and LBY (24.6% Brix) ewes(P = 0.21). These results indicate that, although there were numerical differences, the addition of LBY to the ewes’ diet during late gestation did not significantly improve colostrum quality or passive transfer of immunity in lambs.