scholarly journals The vaccine-elicited immunoglobulin profile in milk after COVID-19 mRNA-based vaccination is IgG-dominant and lacks secretory antibodies

2021 ◽  
Author(s):  
Alisa Fox ◽  
Caroline Norris ◽  
Fatima Amanat ◽  
Susan Zolla-Pazner ◽  
Rebecca L Powell
Keyword(s):  
Enzymatic Degradation ◽  
High Titer ◽  
Passive Immunity ◽  
Gi Tract ◽  
Vaccine Regimen ◽  
Milk Samples ◽  
Specific Igg ◽  
Highly Correlated ◽  
Endpoint Titer ◽  
Secretory Antibodies

The Pfizer/BioNTech and Moderna mRNA-based COVID-19 vaccines are licensed under emergency use authorization, with millions of doses already administered globally [1]. No COVID-19 vaccines are yet under investigation for use in infants or young children. As such, the passive immunity of the antibodies (Abs) provided through milk from a vaccinated person may be one of the only ways to protect this population until pediatric COVID-19 vaccines are licensed. Our early work (as well as an expanded study being published concurrently with this report) examining the milk Ab response after SARS-CoV-2 infection demonstrated that Spike-specific IgA in milk after infection is dominant and highly correlated with a secretory Ab response [2]. Determining if secretory Abs are elicited in milk is critical, as this Ab class is highly stable and resistant to enzymatic degradation in all mucosae - not only in the infant oral/nasal cavity and gut, but in the airways and GI tract as well [3, 4]. Presently, we describe our analysis of the milk Ab response 14 days after completion of an mRNA-based COVID-19 vaccine regimen among 10 individuals. It was evident that unlike the post-infection milk Ab profile, IgG dominates after COVID-19 vaccination. One hundred percent of post-vaccine milk contained significant levels of Spike-specific IgG, with 8/10 samples exhibiting high IgG endpoint titers. Conversely, 6/10 (60%) of post-vaccine samples were positive for Spike specific IgA, with only 1 (10%) exhibiting high IgA endpoint titer. Furthermore, 5/10 (50%) post-vaccine milk samples contained Spike-specific secretory Ab, none of which were found to be high-titer. As our analyses of the immune response in milk to COVID-19 vaccination continues, it will provide a critical opportunity to address huge knowledge gaps, inform the field as to which COVID-19 vaccine, if any, is likely to provide the best milk Ab response, and highlight the need to design improved vaccines with protection of the breastfeeding infant in mind.

scholarly journals Toxicokinetics of Aflatoxin in Pregnant Mice

2010 ◽  
Vol 29 (4) ◽  
pp. 425-431 ◽  
Author(s):  
Salim A. Bastaki ◽  
Nawal Osman ◽  
Jose Kochiyil ◽  
Mohamed Shafiullah ◽  
Rengasamy Padmanabhan ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Gestational Age ◽  
Aflatoxin B1 ◽  
Serum Levels ◽  
Maternal Blood ◽  
Maternal Exposure ◽  
Serum Concentrations ◽  
Gi Tract ◽  
Pregnant Mice ◽  
Highly Correlated

Our objective was to study the toxicokinetics of aflatoxin (AF) in pregnant mice. Aflatoxin B1 (AFB1) was administered intraperitoneally (IP) to groups of pregnant mice in single doses of 20 mg/kg on gestation day (GD) 13 and orally at the same gestational age. Controls received (IP and oral) a proportionate volume of solvent only. Maternal blood was collected at 15, 30, 45, 60, 90, 120, and 150 minutes posttreatment. Their AFB1 contents were determined. Aflatoxin B1 concentrations following maternal exposure to AFB1 were highly correlated with time after exposure. The serum concentrations were predictable and the highest serum levels were seen immediately at 15 minutes in mice given AFs IP and at 30 minutes in those given it orally. The absorption was 5.0 μg/min and elimination was 3.0 μg/min. The toxicokinetics of AFB1 have been delineated. Aflatoxins are easily and rapidly absorbed both from the gastrointestinal tract (GI) tract and through the peritoneum.

Variation in milk cell counts during lactation of British Friesian cattle

1983 ◽  
Vol 36 (3) ◽  
pp. 335-339 ◽  
Author(s):  
P. D. P. Wood ◽  
J. M. Booth
Keyword(s):  
Cell Count ◽  
Clinical Mastitis ◽  
High Cell ◽  
Milk Samples ◽  
The Third ◽  
Cell Counts ◽  
Lactation Curve ◽  
Lactose Concentration ◽  
Highly Correlated ◽  
Friesian Cattle

ABSTRACTA survey was carried out of 1 640 British Friesian heifers calving predominantly in the autumn of 1979. The monthly samples of 1 055 animals showing no reported evidence of udder infection were used to evaluate the parameters of a lactation curve in milk cell count. The model wasC = 190 n−0.4880exp(0·178n)where C is the monthly cell count in millions per 1 during the nth month of lactation. The cell count varied from 230 × 106 in week 1 and 190 × 106 in week 11 to 400 × 106 in week 44 of lactation.On applying the model to the whole sample, milk sampled within a month before or after antibiotic treatment for clinical mastitis contained more than 200 × 106 cells per 1 above the level suggested by the lactation curve. Lactation mean cell counts of treated cows were 400 × 106 cells per 1 higher than those of untreated cows. It was not possible to identify periods in which cows required treatment, or those with high cell counts, by reference to the lactose concentration in the milk samples. Among the untreated cows, the cell count at the third monthly test-day was lower than at any other time, and was more highly correlated with the lactation mean cell count.

scholarly journals Survival of vaccine-induced human milk SARS-CoV-2 IgG and IgA immunoglobulins across simulated human infant gastrointestinal digestion

2021 ◽  
Author(s):  
Myrtani Pieri ◽  
Vicky Nicolaidou ◽  
Irene Paphiti ◽  
Spyros Pipis ◽  
Kyriacos Felekkis ◽  
...  
Keyword(s):  
Human Milk ◽  
Enzymatic Degradation ◽  
Natural Infection ◽  
In Vitro Digestion ◽  
Human Infant ◽  
European Medicines Agency ◽  
Igg Antibodies ◽  
Gi Tract ◽  
Lactating Mothers

Four vaccines have been approved to date by the European Medicines Agency for the management of the COVID-19 pandemic in Europe, with all four being targeted to adults over 18 years of age. One way to protect the younger population such as infants or younger children until pediatric vaccines are licensed is through passive immunity via breastfeeding. Recent evidence points to the fact that human milk contains immunoglobulins (Ig) against the SARS-CoV-2 virus, both after natural infection or vaccination, but it is not known whether these antibodies can resist enzymatic degradation during digestion in the infant gastrointestinal (GI) tract or indeed protect the consumers. Here, we describe our preliminary experiments where we validated commercially available ELISA kits to detect IgA and IgG antibodies in human milk from two lactating mothers vaccinated with either the Pfizer/BioNTech or the Astra Zeneca vaccine, and the effect of a static in vitro digestion protocol on the IgA and IgG concentrations. Our data, even preliminary, provide an indication that the IgA antibodies produced after vaccination with the Pfizer/BioNTech vaccine resist the gastric phase but are degraded during the intestinal phase of infant digestion, whereas the IgGs are more prone to degradation in both phases of digestion. We are in the process of recruiting more individuals to further evaluate the vaccine-induced immunoglobulin profile of breastmilk, and the extent to which these antibodies can resist digestion in the infant GI tract.

Immunoadsorption of IgG onto second antibody covalently attached to Amino-Dylark beads for radioimmunoassays

1990 ◽  
Vol 36 (3) ◽  
pp. 497-500 ◽  
Author(s):  
S E Kakabakos ◽  
G P Evangelatos ◽  
D S Ithakissios
Keyword(s):  
Solid Phase ◽  
High Titer ◽  
Significant Modification ◽  
Assay Performance ◽  
Rabbit Igg ◽  
Assay Tube ◽  
Specific Igg ◽  
Coating Procedure ◽  
Glycol Solution ◽  
Immobilization Method

Abstract We present a solid-phase immobilization method for radioligand assays, using an immunoadsorption coating procedure of anti-triiodothyronine rabbit IgG (anti-T3 IgG) onto second antibody (sheep anti-rabbit IgG) covalently bound to Amino-Dylark beads. The second antibody was in excess, compared with the first antibody, thus eliminating reproducibility problems between immunoadsorptions. Beads coated with second antibody can be used to immobilize a variety of antigen-specific first antibodies. The amount of anti-T3 antibody required for solid-phase T3 radioimmunoassay (RIA) was only 10% more, per assay tube, than that utilized in liquid-phase T3 RIA, in which polyethylene glycol solution was the separation reagent; characteristics of assay performance were comparable. The immobilization procedure requires high-titer antisera or antigen-specific IgG and seems advantageous because of the decrease in antibody requirements without significant modification of antibody functionality.

Peptide Multimers for Binding of Factor VIII Inhibitors.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1224-1224
Author(s):  
Christoph Kessel ◽  
Wolfhart Kreuz ◽  
Katharina Klich ◽  
Frank Vorpahl ◽  
Karin Becker-Peters ◽  
...  
Keyword(s):  
Factor Viii ◽  
Neutralizing Antibodies ◽  
High Titer ◽  
Coagulation Factor ◽  
Peptide Ligands ◽  
Therapeutic Approaches ◽  
Random Peptide ◽  
Fviii Activity ◽  
Specific Igg

Abstract Hemophilia A is an X-chromosome linked bleeding disorder resulting from the absence or nonfunctional expression of coagulation factor VIII (FVIII). About 30% of severe hemophiliacs develop neutralizing antibodies (inhibitors) to FVIII upon treatment with exogenous factor preparations. Specificity of these antibodies is often restricted to functional determinants in the A2 and C2 domain. Phage displayed random peptide libraries were screened with various plasma samples of high titer inhibitor patients and inhibitor specific peptide ligands were selected. In silco mapping of consensus amino acid motifs among peptides revealed conformational epitopes in A2 and C2. Selected ligands partially restored FVIII activity. Equimolar combination of these ligands enhanced blocking of inhibitors in autologous and heterologous patients’ plasma. Peptide ligands were fused to the C-terminal multimerization domain of the C4bp alpha-chain and expressed as multimers in 293T cells. Peptide multimers revealed improved binding of anti-FVIII IgG and prolonged in vitro half-life in comparison to single synthetic peptides. Selected peptide ligands were combined in heteromultimers by co-transfection of respective vectors, resulting in molecules binding both A2- and C2- specific IgG and blocking up to 100% of antibody binding to FVIII. Those molecules could provide a basis for the generation of novel peptide-based therapeutic approaches.

Liquid Chromatography Verification of Tetracycline Residues in Milk and Influence of Milk Fat Lipolysis on the Detection of Antibiotic Residues by Microbial Assays and the Charm II Test

1992 ◽  
Vol 55 (5) ◽  
pp. 374-378 ◽  
Author(s):  
ASE CARLSSON ◽  
LENNART BJÖRCK
Keyword(s):  
Liquid Chromatography ◽  
Milk Fat ◽  
Causative Factor ◽  
Milk Samples ◽  
Negative Results ◽  
Highly Correlated ◽  
Routine Assay ◽  
Tetracycline Residues ◽  
Positive Results

Farm milk samples, which were positive in the routine assay for inhibitory substances detected by the Arla microtest but negative in the Delvotest SP, were used in the study. All samples analyzed gave positive results in the determination of tetracyclines and macrolides by the Charm II microbial receptor tests. To confirm the presence of tetracyclines, liquid chromatography and the Charm II immuno-receptor test were used. All samples, except one, showed negative results in the analyses by both these methods. This suggested that some other factor(s) was causing the observed positive results for tetracyclines and macrolides. Circumstantial evidence indicated that free fatty acids (FFA) may be a causative factor. Consequently, the influence of FFA on the Arla microtest, Valio T101, Delvotest SP, and the tetracycline and macrolide determinations by the Charm II test was investigated. Lipolysis of milk fat was induced by the addition of human blood serum, followed by storage for 24 and 48 h at 4°C. Samples were found to be inhibitory in the Arla microtest and the Valio T101 test at FFA levels of 4–5 mM, whereas the results of the Delvotest SP remained negative. The Charm II counts for tetracyclines and macrolides as determined by the microbial receptor tests were also highly correlated with FFA. It was concluded that lipolysis of milk fat may cause positive results in the microbial nonagar assays and interfere in the confirmation by the Charm II test.

scholarly journals Immunosuppression and mycobacteria other thanMycobacterium tuberculosis: results from patients with and without HIV infection

1989 ◽  
Vol 103 (2) ◽  
pp. 293-300 ◽  
Author(s):  
M. Peters ◽  
D. Schürmann ◽  
A. C. Mayr ◽  
R. Hetzer ◽  
H. D. Pohle ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Gastrointestinal Tract ◽  
Hiv Infection ◽  
Gi Tract ◽  
Aids Patients ◽  
Biopsy Specimens ◽  
Immunosuppressed Patients ◽  
Highly Correlated ◽  
Urine Specimens ◽  
Immunocompetent Patients

SUMMARYInfections caused by mycobacteria other thanMycobacterium tuberculosis(MOTT) have often been described as common in AIDS patients. To evaluate whether infections with MOTT are specific for HIV related immunosuppression or are also frequent in patients with immunosuppression of different aetiology, data on the frequency of isolation from immunosuppressed patients with HIV infection are important. Blood, stool and urine specimens from 134 patients with non-HIV related immunosuppression, and from 55 immunocompetent subjects were examined for mycobacteria. MOTT have been isolated from one immunocompetent person but from none of the immunosuppressed patients. Since in AIDS patients an initial colonization of the gastrointestinal tract (GI-tract) with MOTT is common, GI-tract biopsy specimens from an additional 80 patients were examined microscopically and histologically for mycobacteria. Mycobacteria were not isolated from these specimens.In the same period of time 72 AIDS patients have been examined: 7 (10%) had infections withM. tuberculosiswhereas MOTT have been isolated from 16 (22%) of these patients. Mycobacteria have been found only rarely in immunocompetent patients and have not been isolated from patients with non-HIV related immunosuppression. The isolation of MOTT is highly correlated with an HIV-related immunosuppression.

scholarly journals Assignment of Serotype-Specific IgG1, IgG2, and IgA Weight-Based Antibody Units to the Human Pneumococcal Standard Reference Serum, 007sp

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Scott Jones ◽  
Kier Finnegan ◽  
Jae Hee Wee ◽  
Polly D’Argoeuves ◽  
Lucy Roalfe ◽  
...  
Keyword(s):  
Immunosorbent Assay ◽  
Critical Period ◽  
World Health ◽  
Enzyme Linked Immunosorbent Assay ◽  
Functional Assays ◽  
Reference Serum ◽  
Specific Igg ◽  
Highly Correlated ◽  
Health Organization ◽  
Made In

ABSTRACTIn 2011, the human pneumococcal standard reference serum, 007sp, was established as a replacement for the previous standard, lot 89SF, supplies of which were dwindling. The pneumococcal reference serum is used primarily in the standardized pneumococcal enzyme-linked immunosorbent assay (World Health Organization reference enzyme-linked immunosorbent assay) but has also been used in functional assays. Serotype-specific IgG values for 24 pneumococcal capsular serotypes have previously been assigned to 007sp by bridging to the original values derived for lot 89SF. In this study, by bridging to existing values in lot 89SF, we assign weight-based serotype-specific IgA, IgG1, and IgG2 to 007sp for 11 pneumococcal capsular serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F), as well as serotype 19A-specific IgA. Concentrations for serotype-specific IgA, IgG1, and IgG2 present in 007sp were comparable to those previously assigned to lot 89SF. In addition, the concentration of serotype-specific IgG1 plus IgG2 assigned to 007sp significantly correlated to previously assigned 007sp IgG values. The accuracy of antibody assignments to 007sp from lot 89SF was assessed by comparing the concentration of serotype-specific IgA, IgG1, and IgG2 in 16 unknown samples using both 007sp and lot 89SF as the standard. Interpolated values for the unknown samples were highly correlated with averageR2values of 0.9729, 0.9951, and 0.9933 for IgA, IgG1, and IgG2, respectively, for all serotypes demonstrating the precise nature assignments to 007sp made in this study. Nonparallelism between 007sp and lot 89SF has precluded the derivation of serotype-specific IgM values.IMPORTANCEA well-characterized antibody standard is an indispensable reagent for use in assays designed to measure antibodies with precision and where assays between laboratories need to be comparable. The human pneumococcal standard reference serum, lot 89SF, greatly facilitated the standardization of enzyme-linked immunosorbent assay methodologies during a critical period when the first pneumococcal polysaccharide-conjugate vaccines were being evaluated for licensure. Due to dwindling supplies of lot 89SF, a new reference standard, 007sp, was produced in 2011. Understanding the isotype and subclass composition of either natural or vaccine induced responses to pathogens has assumed increasing importance. In this study, we have assigned IgA, IgG1, and IgG2 values to pneumococcal serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F by bridging to existing values in lot 89SF.

scholarly journals SARS-CoV-2 RNA and antibody detection in human milk from a prospective multicenter study in Spain

2021 ◽  
Author(s):  
Christine Bauerl ◽  
Walter Randazzo ◽  
Gloria Sanchez ◽  
Marta Selma-Royo ◽  
Elia Garcia-Verdevio ◽  
...  
Keyword(s):  
Breast Milk ◽  
Scientific Evidence ◽  
Individual Variability ◽  
Antibody Detection ◽  
Passive Immunity ◽  
Nucleocapsid Gene ◽  
Milk Samples ◽  
Specific Protocol ◽  
Clinical Records ◽  
The Impact

Background: During the COVID-19 pandemic in 2020, breastfeeding in women positive for SARS-CoV-2 was compromised due to contradictory data regarding potential viral transmission. However, growing evidence confirms the relevant role of breast milk in providing passive immunity by generating and transmitting specific antibodies against the virus. Thus, our study aimed to develop and validate a specific protocol to detect SARS-CoV-2 in breast milk matrix as well as to determine the impact of maternal SARS-CoV-2 infection on presence, concentration, and persistence of specific SARS-CoV-2 antibodies. Study design/Methods: A prospective multicenter longitudinal study in Spain was carried out from April to December 2020. A total of 60 mothers with SARS-CoV-2 infection and/or recovered from COVID-19 were included (n=52 PCR-diagnosed and n=8 seropositive). Data from maternal-infant clinical records and symptomatology were collected. A specific protocol was validated to detect SARS-CoV-2 RNA in breast milk, targeting the N1 region of the nucleocapsid gene and the envelope (E) gene. Presence and levels of SARS-CoV-2 specific immunoglobulins (Igs) -IgA, IgG, and IgM- in breast milk samples from COVID-19 patients and from 13 women before the pandemic were also evaluated. Results: All breast milk samples showed negative results for SARS-CoV-2 RNA presence. We observed high intra- and inter-individual variability in the antibody response to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein for each of the three isotypes IgA, IgM and IgG. Protease domain (MPro) antibodies were also detected in milk. In general, 82.9 % of the milk samples were positive for at least one of the three antibody isotypes, being 52.86 % of those positive for all three Igs. Positivity rate for IgA was relatively stable over time (65.2-87.5 %), whereas it raised continuously for IgG (47.8 % the first ten days to 87.5 % from day 41 up to day 206 post-PCR confirmation). Conclusions: Considering the lack of evidence for SARS-CoV-2 transmission through breast milk, our study confirms the safety of breastfeeding practices and highlights the relevance of virus-specific SARS-CoV-2 antibody transfer, that would provide passive immunity to breastfed infants and protect them against COVID-19 disease. This study provides crucial data to support official breastfeeding recommendations based on scientific evidence.

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