scholarly journals Human Cytomegalovirus Reactivation During Lactation: Impact of Antibody Kinetics and Neutralization in Blood and Breast Milk

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 338 ◽  
Author(s):  
Katrin Lazar ◽  
Tabea Rabe ◽  
Rangmar Goelz ◽  
Klaus Hamprecht
Keyword(s):  
Breast Milk ◽  
Human Cytomegalovirus ◽  
Igg Antibodies ◽  
Binding Assays ◽  
Virus Shedding ◽  
Milk Whey ◽  
Viral Loads ◽  
Cytomegalovirus Reactivation ◽  
Specific Igg ◽  
Functional Antibodies

Human cytomegalovirus (HCMV) is shed into breast milk in nearly every seropositive woman during lactation. This reactivation shows mostly a self-limited, unimodal course. The dynamics and functional role of HCMV-specific-IgG in breast milk and in plasma during reactivation are unknown. Milk whey viral loads were monitored with real-time PCR in 18 HCMV-seropositive mothers over two months postpartum. HCMV-antibody binding assays (ECLIA) and antigen-specific immunoblotting were performed from plasma and corresponding milk samples. Epithelial-cell-specific neutralization was used to analyze functional antibodies in plasma- and whey-pools. Viral loads in milk whey showed unimodal courses in 15 of 18 mothers with peak viral loads around one month postpartum. HCMV-specific-IgG-antibodies increased significantly in plasma and milk whey during reactivation. The mean levels of plasma IgG were about 275-fold higher than in whey. Only antibodies against tegument protein p150 were continuously expressed in both compartments. Anti-glycoprotein-B1 IgG-antibodies were variably expressed in whey, but continuously in plasma. Neutralization assays showed 40-fold higher NT-50 values in plasma compared to whey at two months postpartum. During reactivation, HCMV-specific-IgG reactivities and neutralizing capacities are much lower in whey than in plasma. Therefore, their specific role in the decrease and discontinuation of virus-shedding in milk remains unclear.

New short-term heat inactivation method of cytomegalovirus (CMV) in breast milk: impact on CMV inactivation, CMV antibodies and enzyme activities

2019 ◽  
Vol 104 (6) ◽  
pp. F604-F608 ◽  
Author(s):  
Jens Maschmann ◽  
Denise Müller ◽  
Katrin Lazar ◽  
Rangmar Goelz ◽  
Klaus Hamprecht
Keyword(s):  
Breast Milk ◽  
Enzyme Activities ◽  
Primary Source ◽  
Wild Type Virus ◽  
Heat Inactivation ◽  
Target Cells ◽  
Igg Antibodies ◽  
Wild Type ◽  
Short Term ◽  
Milk Whey

ObjectivesBreast milk (BM) is the primary source of cytomegalovirus (CMV) transmission to premature infants with potentially harmful consequences. We therefore wanted to evaluate temperature and duration of short-term BM pasteurisation with respect to CMV inactivation, effect on CMV-IgG antibodies and BM enzyme activities.Methods116 artificially CMV-spiked BM and 15 wild-type virus-infected samples were subjected for 5 s to different temperatures (55°C–72°C). CMV-IE-1 expression in fibroblast nuclei was assessed using the milk whey fraction in short-term microculture. BM lipase and alkaline phosphatase (AP) activities and CMV binding using CMV-recomLine immunoblotting and neutralising antibodies using epithelial target cells were analysed before and after heating.ResultsA minimum of 5 s above 60°C was necessary for CMV inactivation in both CMV-AD-169 spiked and wild-type infected BM. Lipase was very heat sensitive (activities of 54% at 55°C, 5% at 60°C and 2% at 65°C). AP showed activities of 77%, 88% and 10%, respectively. CMV-p150 IgG antibodies were mostly preserved at 62°C for 5 s.ConclusionOur results show that short-term pasteurisation of BM at 62°C for 5 s might be efficient for CMV inactivation and reduces loss of enzyme activities, as well as CMV binding, and functional CMV antibodies.

scholarly journals Human Cytomegalovirus (HCMV) Reactivation in the Mammary Gland Induces a Proinflammatory Cytokine Shift in Breast Milk

2020 ◽  
Vol 8 (2) ◽  
pp. 289 ◽  
Author(s):  
Tabea Rabe ◽  
Katrin Lazar ◽  
Christoffer Cambronero ◽  
Rangmar Goelz ◽  
Klaus Hamprecht
Keyword(s):  
Mammary Gland ◽  
Breast Milk ◽  
Human Cytomegalovirus ◽  
Proinflammatory Cytokine ◽  
Human Breast Milk ◽  
Dna Dynamics ◽  
Cytokine Network ◽  
Milk Whey ◽  
Mothers Of Preterm Infants ◽  
The Impact

A locally restricted human cytomegalovirus (HCMV) reactivation in the mammary gland commonly occurs in nearly every IgG-seropositive breastfeeding mother. This unique phenomenon can therefore be used to study the reactivation process in an immunocompetent healthy host. Breast milk contains a variety of immunoactive compounds, including immune cells, antibodies, growth factors, and cytokines supporting the newborn’s immature immune system. To characterize the impact of HCMV reactivation on breast milk cytokines, we analyzed longitudinal breast milk samples of four IgG-seropositive and three IgG-seronegative mothers of preterm infants using Proximity Extension Assay (PEA) technology (Olink Proteomics, Uppsala, Sweden). Cytokine profiling revealed elevated cytokine levels in IgG-seropositive mothers’ milk whey. Reactivating mothers showed higher levels of CC-chemokines (MCP-2, CCL19, and CCL20) and CXC-chemokines (IL-8, CXCL9, CXCL10, and CXCL11), such as the proinflammatory cytokine IL-17C, glycoprotein CD5, and TNFSF14. HCMV reactivation seems to influence the cytokine profile in human breast milk. This work could open the door for further studies analyzing distinct relations of the cytokine network as well as phenotypical and functional T cell properties in background of HCMV DNA dynamics in early lactation.

scholarly journals Induction of SARS-Cov-2-Specific IgG and IgA in Serum and Milk with Different SARS-CoV-2 Vaccines in Breastfeeding Women: A Cross-Sectional Study in Northern Spain

2021 ◽  
Vol 18 (16) ◽  
pp. 8831
Author(s):  
Carolina Lechosa-Muñiz ◽  
María Paz-Zulueta ◽  
Jose Manuel Mendez-Legaza ◽  
Juan Irure-Ventura ◽  
Rocío Cuesta González ◽  
...  
Keyword(s):  
Breast Milk ◽  
Adverse Reactions ◽  
Protein S ◽  
Vaccine Safety ◽  
Cross Sectional Study ◽  
Igg Antibodies ◽  
Northern Spain ◽  
Cross Sectional ◽  
Mean Values ◽  
Specific Igg

Breastfeeding mothers were excluded from the clinical trials conducted for vaccines against SARS-COV2. Since the start of the vaccination, some doubts have arisen regarding its compatibility with breastfeeding. The aim of this study was to analyse the presence of anti-SARS-CoV-2 antibodies in breast milk and serum (IgG and IgA) of vaccinated breastfeeding women. The main variables of the observational study were: adverse related events after vaccination and determination of the presence of IgG and IgA isotypes antibodies in serum and in breast milk of vaccinated women against the SARS-CoV-2 antigens. Results: 110 breastfeeding mothers were included; 70 women (63.6%) were vaccinated with two doses of BNT162b2, 20 women (18.2%) with two doses of mRNA-1273, and 20 women (18.2%) with a single dose of ChAdOx1-S. Regarding adverse reactions and vaccine safety, 38 women had no adverse reactions; 20 (18.2%) had general malaise or adenopathies; 10 (9.1%) had a headache; and 7 (6.4%) had fever. When analysing IgG antibodies, significantly higher levels of antibodies were found in serum and breast milk from mothers vaccinated with BNT162b2 or mRNA-1273 vs. ChAdOx1-S (p < 0.001 and p = 0.001, respectively). Analysing IgA antibodies, significant differences were found when comparing mean values in serum from mothers vaccinated with BNT162b2 or mRNA-1273 vs. ChAdOx1-S (0.12, 0.16, and 0.02, respectively; p < 0.001) and breast milk of mothers vaccinated when comparing BNT16b2 vs. ChAdOx1-S. All vaccinated breastfeeding mothers had serum anti-S1 IgG antibodies in response to vaccination against SARS-CoV-2, regardless of the commercial vaccine administered. Conclusions: the anti-SARS-CoV-2 vaccines were well tolerated by the mothers and the breastfed infant. In addition, breastfeeding mothers offer their infants IgA and IgG isotype antibodies directed against SARS-CoV-2 protein S in breast milk.

scholarly journals Role of Milk Whey in the Transmission of Human Cytomegalovirus Infection by Breast Milk

1996 ◽  
Vol 40 (3) ◽  
pp. 201-204 ◽  
Author(s):  
Hideomi Asanuma ◽  
Kei Numazaki ◽  
Nobuo Nagata ◽  
Tomoyuki Hotsubo ◽  
Kiyotaka Horino ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Cytomegalovirus ◽  
Cytomegalovirus Infection ◽  
Milk Whey ◽  
Human Cytomegalovirus Infection

scholarly journals Detection of Genotype-Specific Antibody Responses to Glycoproteins B and H in Primary and Non-Primary Human Cytomegalovirus Infections by Peptide-Based ELISA

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 399
Author(s):  
Federica Zavaglio ◽  
Loretta Fiorina ◽  
Nicolás M. Suárez ◽  
Chiara Fornara ◽  
Marica De Cicco ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
Background Strain ◽  
Specific Igg ◽  
Cytomegalovirus Infections ◽  
Specific Igg Antibodies

Background: Strain-specific antibodies to human cytomegalovirus (HCMV) glycoproteins B and H (gB and gH) have been proposed as a potential diagnostic tool for identifying reinfection. We investigated genotype-specific IgG antibody responses in parallel with defining the gB and gH genotypes of the infecting viral strains. Methods: Subjects with primary (n = 20) or non-primary (n = 25) HCMV infection were studied. The seven gB (gB1-7) and two gH (gH1-2) genotypes were determined by real-time PCR and whole viral genome sequencing, and genotype-specific IgG antibodies were measured by a peptide-based enzyme-linked immunosorbent assay (ELISA). Results: Among subjects with primary infection, 73% (n = 8) infected by gB1-HCMV and 63% (n = 5) infected by gB2/3-HCMV had genotype-specific IgG antibodies to gB (gB2 and gB3 are similar in the region tested). Peptides from the rarer gB4-gB7 genotypes had nonspecific antibody responses. All subjects infected by gH1-HCMV and 86% (n = 6) infected by gH2-HCMV developed genotype-specific responses. Among women with non-primary infection, gB and gH genotype-specific IgG antibodies were detected in 40% (n = 10) and 80% (n = 20) of subjects, respectively. Conclusions: Peptide-based ELISA is capable of detecting primary genotype-specific IgG responses to HCMV gB and gH, and could be adopted for identifying reinfections. However, about half of the subjects did not have genotype-specific IgG antibodies to gB.

scholarly journals Multiple-Strain Infections of Human Cytomegalovirus With High Genomic Diversity Are Common in Breast Milk From Human Immunodeficiency Virus–Infected Women in Zambia

2019 ◽  
Vol 220 (5) ◽  
pp. 792-801 ◽  
Author(s):  
Nicolás M Suárez ◽  
Kunda G Musonda ◽  
Eric Escriva ◽  
Margaret Njenga ◽  
Anthony Agbueze ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Breast Milk ◽  
Human Cytomegalovirus ◽  
Developed Countries ◽  
Genomic Diversity ◽  
Viral Loads ◽  
Strain Diversity ◽  
Milk Samples ◽  
Immunodeficiency Virus ◽  
Hiv Negative

Abstract Background In developed countries, human cytomegalovirus (HCMV) is a major pathogen in congenitally infected and immunocompromised individuals, where multiple-strain infection appears linked to disease severity. The situation is less documented in developing countries. In Zambia, breast milk is a key route for transmitting HCMV and carries higher viral loads in human immunodeficiency virus (HIV)–infected women. We investigated HCMV strain diversity. Methods High-throughput sequence datasets were generated from 28 HCMV-positive breast milk samples donated by 22 mothers (15 HIV-infected and 7 HIV-negative) at 4–16 weeks postpartum, then analyzed by genome assembly and novel motif-based genotyping in 12 hypervariable HCMV genes. Results Among the 20 samples from 14 donors (13 HIV-infected and one HIV-negative) who yielded data meeting quality thresholds, 89 of the possible 109 genotypes were detected, and multiple-strain infections involving up to 5 strains per person were apparent in 9 HIV-infected women. Strain diversity was extensive among individuals but conserved compartmentally and longitudinally within them. Genotypic linkage was maintained within hypervariable UL73/UL74 and RL12/RL13/UL1 loci for virus entry and immunomodulation, but not between genes more distant from each other. Conclusions Breast milk from HIV-infected women contains multiple HCMV strains of high genotypic complexity and thus constitutes a major source for transmitting viral diversity.

scholarly journals Multiple-Strain Infections of Human Cytomegalovirus with High Genomic Diversity are Common In Breast Milk from HIV-Positive Women in Zambia

2018 ◽  
Author(s):  
Nicolás M. Suárez ◽  
Kunda G. Musonda ◽  
Eric Escriva ◽  
Margaret Njenga ◽  
Anthony Agbueze ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Cytomegalovirus ◽  
Developed Countries ◽  
Genomic Diversity ◽  
Hiv Positive ◽  
Viral Loads ◽  
Strain Diversity ◽  
Milk Samples ◽  
Hiv Positive Women ◽  
Hiv Negative

ABSTRACTBackgroundIn developed countries, human cytomegalovirus (HCMV) is a major pathogen in congenitally infected and immunocompromised individuals, in whom multiple-strain infection is linked to disease severity. The situation is less documente in developing countries. In Zambia, breast milk is a key route for transmitting HCMV and carries higher viral loads in HIV-positive women. We investigated HCMV strain diversity.MethodsHigh-throughput sequence datasets were generated from 28 HCMV-positive breast milk samples donated by 22 mothers (15 HIV-positive and seven HIV-negative) at 4 or 16 weeks (or both) postpartum and analysed by genotyping 12 hypervariable HCMV genes.ResultsAmong the 20 samples from 14 donors (13 HIV-positive and one HIV-negative) that yielded data meeting quality thresholds, 89 of the possible 109 genotypes were detected, and multiple-strain infections involving up to five strains per person were apparent in nine HIV-positive women. Strain diversity was extensive among individuals but conserved compartmentally and longitudinally within them. Genotypic linkage was maintained within the hypervariable UL73/UL74 and RL12/RL13/UL1 loci for virus-entry and immunomodulation, but not between genes more distant from each other.ConclusionsBreast milk from HIV-positive women contains multiple HCMV strains of high genotypic complexity and thus constitutes a major source for transmitting viral diversity.

scholarly journals Viral Load in Breast Milk Correlates with Transmission of Human Cytomegalovirus to Preterm Neonates, but Lactoferrin Concentrations Do Not

2001 ◽  
Vol 8 (4) ◽  
pp. 818-821 ◽  
Author(s):  
B. W. A. van der Strate ◽  
M. C. Harmsen ◽  
P. Schäfer ◽  
P. J. Swart ◽  
T. H. The ◽  
...  
Keyword(s):  
Viral Load ◽  
Breast Milk ◽  
Preterm Infants ◽  
Human Cytomegalovirus ◽  
Virus Transmission ◽  
Preterm Neonates ◽  
Viral Dna ◽  
Viral Loads

ABSTRACT In vitro, lactoferrin (LF) strongly inhibits human cytomegalovirus (HCMV), which led us to hypothesize that in vivo HCMV might also be inhibited in secretions with high LF concentrations. In breast milk, high viral loads observed as high viral DNA titers tended to coincide with higher LF levels. However, the LF levels did not correlate to virus transmission to preterm infants. The viral load in the transmitting group was highest compared to the nontransmitting group. We conclude that viral load in breast milk is an important factor for transmission of the virus.

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