Antibodies In Human Milk Research Articles

SARS-CoV-2 infection induces human milk antibodies capable of mediating multiple functional activities

SARS-CoV-2 infection induces human milk antibodies capable of mediating multiple functional activities

Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG.

BACKGROUNDThe use of high-throughput technologies has enabled rapid advancement in the knowledge of host immune responses to pathogens. Our objective was to compare the repertoire, protection, and maternal factors associated with human milk antibodies to infectious pathogens in different economic and geographic locations.METHODSUsing multipathogen protein microarrays, 878 milk and 94 paired serum samples collected from 695 women in 5 high and low-to-middle income countries (Bangladesh, Finland, Peru, Pakistan, and the United States) were assessed for specific IgA and IgG antibodies to 1,607 proteins from 30 enteric, respiratory, and bloodborne pathogens.RESULTSThe antibody coverage across enteric and respiratory pathogens was highest in Bangladeshi and Pakistani cohorts and lowest in the U.S. and Finland. While some pathogens induced a dominant IgA response (Campylobacter, Klebsiella, Acinetobacter, Cryptosporidium, and pertussis), others elicited both IgA and IgG antibodies in milk and serum, possibly related to the invasiveness of the infection (Shigella, enteropathogenic E. coli "EPEC", Streptococcus pneumoniae, Staphylococcus aureus, and Group B Streptococcus). Besides the differences between economic regions and decreases in concentrations over time, human milk IgA and IgG antibody concentrations were lower in mothers with high BMI and higher parity, respectively. In Bangladeshi infants, a higher specific IgA concentration in human milk was associated with delayed time to rotavirus infection, implying protective properties of antirotavirus antibodies, whereas a higher IgA antibody concentration was associated with greater incidence of Campylobacter infection.CONCLUSIONThis comprehensive assessment of human milk antibody profiles may be used to guide the development of passive protection strategies against infant morbidity and mortality.FUNDINGBill and Melinda Gates Foundation grant OPP1172222 (to KMJ); Bill and Melinda Gates Foundation grant OPP1066764 funded the MDIG trial (to DER); University of Rochester CTSI and Environmental Health Sciences Center funded the Rochester Lifestyle study (to RJL); and R01 AI043596 funded PROVIDE (to WAP).

Persistence and Efficacy of Maternal COVID-19 Vaccine-Induced Antibodies in Human Milk: A Comprehensive Meta-Analysis

Abstract Background: The ongoing global health challenge posed by the COVID-19 pandemic has necessitated a thorough examination of vaccine efficacy, particularly the transfer of vaccine-induced immunity to infants via human milk. This meta-analysis aims to explore the persistence and efficacy of COVID-19 vaccine-induced antibodies in human milk, offering insights into passive immunity transfer to breastfeeding infants. Methods: We conducted a systematic review and meta-analysis of peer-reviewed studies published from January 2021 to December 2023, extracted from databases such as PubMed, Scopus, and Web of Science. Our focus was on studies measuring SARS-CoV-2-specific antibodies (IgA and IgG) in human milk following maternal COVID-19 vaccination. Results: Fifteen studies involving 1,200 lactating mothers who received mRNA COVID-19 vaccines were included. The analysis highlighted a consistent presence of SARS-CoV-2-specific IgA and IgG antibodies in human milk, persisting for up to six months post-vaccination. Conclusion: The results highlight the noteworthy transmission of COVID-19 antibodies via human milk, suggesting an extended duration of possible protection for neonates against SARS-CoV-2 infection. This argues in favor of immunizing nursing mothers as a preemptive public health strategy to provide their children passive immunity.

SARS-CoV-2 Antibodies in Human Milk After mRNA and Adenovector-Based Vaccination: A Systematic Review and Meta-Analysis.

SARS-CoV-2 specific antibodies exist in human milk expressed by lactating parents after vaccination. In the existing research, the effects of vaccine types on human milk are inconsistent. This study aims to perform a systematic review and meta-analysis of the existing observational studies to compare the positive rates of SARS-CoV-2 specific antibodies in human milk according to mRNA and adenovector-based vaccination. PubMed, Web of Science, Elsevier Science Direct and Cochrane Library databases were systematically searched for relevant articles published from December 30, 2019 to February 15, 2023. Observational studies were considered eligible provided they reported data on SARS-CoV-2 specific antibodies in human milk. The risk of bias in non-randomized studies of interventions (ROBINS-I) tool, the Newcastle-Ottawa Scale (NOS), and the Agency for Healthcare Research and Quality (AHRQ) were used to assess risk of bias. Seven studies, including 511 lactating participants, were included in this review and meta-analysis. The positive rate of SARS-CoV-2 IgA is higher in mRNA vaccine groups than in adenovector-based vaccine groups (OR = 4.80, 95% CI [3.04, 7.58], p < 0.001). The positive rate of SARS-CoV-2 IgG was higher in mRNA vaccines than in adenovector-based vaccines. Compared to adenovector-based vaccines, mRNA vaccines present a higher positivity rate of IgA and IgG in human milk after vaccination. In other words, mRNA vaccinations may offer breastfed children a higher level of protection than adenovector-based vaccinations. Further high-quality data is still required to substantiate these findings.

Persistence of COVID-19 Human Milk Antibodies After Maternal COVID-19 Vaccination: Systematic Review and Meta-Regression Analysis.

The World Health Organization (WHO) declared COVID-19 a pandemic. The Centers for Disease Control and Prevention (CDC), WHO, and American College of Obstetricians and Gynecologists (ACOG) recommend vaccination of pregnant and lactating women, aiming to protect both mothers and their infants through transplacental and human milk antibody transmission. This study aims to assess the quantity of antibodies in human milk and determine the effect of time, vaccine type, and dose on antibody level. Single-arm prospective observational studies reportingthe COVID-19-specific antibody level in human milk after COVID-19 vaccination during pregnancy or lactation were included. PubMed, Scopus, Cochrane, EBSCO, and Web of Science were searched from December 2019 to November22, 2022. Data were extracted in a uniform Google sheet.A total of 2657 studies were identified. After the removal of duplicates and screening, 24 studies were included in the systematic review and meta-regression. Human milk COVID-19-specific antibody levels increased with subsequent vaccine doses, as reflected by a positive relationship for the second (coefficient=0.91, P-value 0.043 for IgA and coefficient=1.77, P-value 0.009 for IgG) and third (coefficient=1.23, P-value 0.0029 for IgA and coefficient=3.73, P-value 0.0068 for IgG)doses. The antibody level exhibited a weak positive relationship with the follow-up time (coefficient=0.13, P-value 0.0029 for IgA and coefficient=0.18, P-value 0.016 for IgG). Only one of the 38 infants showed detectable COVID-19 IgM and IgA antibody levels in their blood. There wasan increase in the neutralizing activity of COVID-19 antibodies in human milk following the COVID-19 vaccination. From the analysis of published data, we found high positive levels of antibodies in human milk that increased with subsequent doses. Additionally, the human milk antibodies exhibit a positive neutralizing effect. Only one infant had detectable COVID-19 IgM+IgA antibodies in the blood. Further research is needed to discuss infant protection through a mother'svaccination.

Physical activity in lactating women influences SARS-CoV-2-specific antibodies in human milk

BackgroundModerate exercise results in a significant increase in serum and salivary immunoglobulins. Maternal physical activity might therefore also be a factor influencing antibody levels in human milk. This study aims to determine the influence of physical activity on SARS-CoV-2-specific Immunoglobulin A (IgA) in human milk and Immunoglobulin G (IgG) in serum. MethodsIn this prospective cross-sectional cohort study, all lactating women in the Netherlands were eligible to participate. SARS-CoV-2-specific IgA in human milk and IgG in serum were determined using an enzyme-linked immunosorbent assay (ELISA). Data on performed physical activity was collected using the Short Questionnaire to Assess Health enhancing physical activity (SQUASH), which includes intensity and duration of the performed activity. FindingsIn total, 356 out of 2312 lactating women tested positive for SARS-CoV-2-specific antibodies in serum. Of them, 323 filled in the questionnaire and were included in the analysis. An association between the activity score and SARS-CoV-2-specific antibodies in human milk (B = 1·035, 95·0% CI = 1·019 to 1·052, p = 0·042) and serum (B = 1·019, 95·0% CI = 1·009 to 1·029, p = 0·048) was demonstrated. No association was found between the duration of physical activity and SARS-CoV-2-specific antibodies in human milk or serum. InterpretationOur findings suggest that physical activity is beneficial for the levels of SARS-CoV-2-specific antibodies in human milk and serum, with the intensity of the physical activity being the most important contributor to this relationship. A higher level of antibodies in human milk might provide better immunological protection for infants against COVID-19.

Impact of maternal SARS-CoV-2 booster vaccination on blood and breastmilk antibodies.

Maternal COVID-19 vaccination could protect infants who are ineligible for vaccine through antibody transfer during pregnancy and lactation. We measured the quantity and durability of SARS-CoV-2 antibodies in human milk and infant blood before and after maternal booster vaccination. Prospective cohort of lactating women immunized with primary and booster COVID-19 vaccines during pregnancy or lactation and their infants. Milk and blood samples from October 2021 to April 2022 were included. Anti-nucleoprotein (NP) and anti-receptor binding domain (RBD) IgG and IgA in maternal milk and maternal and infant blood were measured and compared longitudinally after maternal booster vaccine. Forty-five lactating women and their infants provided samples. 58% of women were anti-NP negative and 42% were positive on their first blood sample prior to booster vaccine. Anti-RBD IgG and IgA in milk remained significantly increased through 120-170 days after booster vaccine and did not differ by maternal NP status. Anti-RBD IgG and IgA did not increase in infant blood after maternal booster. Of infants born to women vaccinated in pregnancy, 74% still had positive serum anti-RBD IgG measured on average 5 months after delivery. Infant to maternal IgG ratio was highest for infants exposed to maternal primary vaccine during the second trimester compared to third trimester (0.85 versus 0.29; p<0.001). Maternal COVID-19 primary and booster vaccine resulted in robust and long-lasting transplacental and milk antibodies. These antibodies may provide important protection against SARS-CoV-2 during the first six months of life.

Vaccination Beliefs and Attitudes of Lactating People During the SARS-CoV-2 Pandemic.

Pregnant and recently pregnant people have lower vaccination rates against SARS-CoV-2 than the general population, despite increased risk of adverse outcomes from infection. Little is known about vaccine hesitancy in this population. To characterize SARS-CoV-2 and other vaccine attitudes of lactating people who accepted the SARS-CoV-2 vaccine, describing their vaccine experiences to further contextualize their beliefs. A prospective cross-sectional online survey design was used. We administered the survey to 100 lactating people in Pennsylvania from April to August 2021, upon enrollment into a longitudinal study investigating SARS-CoV-2 vaccine antibodies in human milk. This survey assessed SARS-CoV-2 vaccine attitudes, vaccine counseling from providers, and vaccine decision making. Associations between vaccination timing and beliefs were analyzed by Pearson chi-square. Of 100 respondents, all received ≥ 1 SARS-CoV-2 vaccine before or shortly after enrollment, with 44% (n = 44) vaccinated in pregnancy and 56% (n = 56) while lactating. Participants reported vaccination counseling by obstetric (n = 48; 70%) and pediatric (n = 25; 36%) providers. Thirty-two percent (n = 32) received no advice on SARS-CoV-2 vaccination from healthcare providers, while 69% (n = 69) were counseled that vaccination was safe and beneficial.While 6% (n = 6) and 5% (n = 5) reported concerns about the safety of maternal vaccines for lactating people or their infants, respectively, 12% (n = 12) and 9% (n = 9) expressed concerns about the safety of maternal SARS-CoV-2 vaccination in particular. Despite high uptake of SARS-CoV-2 vaccine among participants, safety concerns persisted, with many reporting a lack of direct counseling from providers. Future research should investigate how variability in provider counseling affects SARS-CoV-2 vaccine uptake in perinatal populations.

Characterization of SARS-CoV-2 antibodies in human milk from 21 women with confirmed COVID-19 infection

BackgroundOne potential mechanism for protection from SARS-CoV-2 in children is through passive immunity via breast milk from a mother infected with the novel coronavirus. The primary objectives of this study were to establish the presence of SARS-CoV-2-specific IgA and IgG and to characterize the antigenic regions of SARS-CoV-2 proteins that were reactive with antibodies in breast milk.MethodsBetween March 2020 and September 2020, 21 women with confirmed SARS-CoV-2 infection were enrolled in Mommy’s Milk. Participants donated serial breast milk samples around their time of illness. Breast milk samples were used to probe a multi-coronavirus protein microarray containing full-length and variable-length overlapping fragments of SARS-CoV-2 proteins. Samples were also tested against S and N proteins by electrochemiluminescence assay.ResultsThe breast milk samples contained IgA reactive with a variety of SARS-CoV-2 antigens. The most IgA-reactive SARS-CoV-2 proteins were N (42.9% of women responded to ≥1 N fragment) and S proteins (23.9% responded to ≥1 fragment of S1 or S2). IgG responses were similar. A striking observation was the dissimilarity between mothers in antibody recognition, giving distinct antibody reactivity and kinetic profiles.ConclusionsIndividual COVID-19 cases had diverse and unique milk IgA profiles following the onset of symptoms.ImpactIn this observational longitudinal case series of 21 women with confirmed SARS-CoV-2 infection, IgA binding to SARS-CoV-2 proteins detected by orthologous proteome microarray and electrochemiluminescence assays was observed in >75% of women, but there was heterogeneity in which antigens and how many were reactive between women.Immunological profiles of protein regions recognized by each woman were distinct.Diverse repertoires of mucosal breast milk antibody to SARS-CoV-2 reflect heterogeneous passive transfer of maternal antibody to exposed breastfeeding infants.

Increase in SARS-CoV-2 RBD-Specific IgA and IgG Antibodies in Human Milk From Lactating Women Following the COVID-19 Booster Vaccination.

The United States Centers for Disease Control and Prevention recommended a third dose or booster of the Pfizer-BioNTech Comirnaty (BNT162b2) COVID-19 mRNA vaccine in September 2021 for high-risk individuals. Pregnant and high-risk lactating women were encouraged to receive the booster to obtain potential prolonged protection for themselves and their infants. To investigate the ability of the booster vaccine to increase IgA and IgG antibodies specific to the receptor-binding domain of the SARS-CoV-2 spike protein in human milk compared to levels pre-booster. This was a prospective one-group study with a pretest-posttest design. Six of 12 participants were recruited prospectively. Participants were instructed to collect ≥ 2 ounces of milk in the morning at 30 days and 1-day pre-booster, and 7, 14, 21, 30, 45, and 60 days post-booster. Levels of IgA and IgG antibodies specific to the receptor-binding domain of the SARS-CoV-2 spike protein were quantified in human milk via an ELISA assay. We found a significant increase in anti-receptor-binding domain-specific IgA and IgG antibodies in human milk 1-2 weeks after the Pfizer-BioNTech booster and at the study endpoint (45- and 60-days post-booster). This suggests that the booster vaccination enhances SARS-CoV-2 specific immunity in human milk, which may be protective for infants.

Antibodies in the breastmilk of COVID-19 recovered women

ObjectiveHuman milk contains antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which may serve as a protective factor through passive immunization in infants. The objective of this study was to measure the levels of anti-SARS-CoV-2 IgG and IgA in human milk and serum after a SARS-CoV-2 infection.DesignBreast milk and serum samples from 72 lactating mothers with confirmed SARS-CoV-2 asymptomatic or symptomatic infection were collected 1-229 days after the onset of clinical symptoms related to COVID-19. Seventeen mothers with no history of COVID-19 served as a control group. Enzyme-Linked ImmunoSorbent Assay was performed to analyze antibodies against SARS-CoV-2.ResultsSARS-CoV-2-IgA human milk antibodies were detected in mothers and their concentrations were consistently higher than SARS-CoV-2-IgG antibodies. The serum and breastmilk samples of women with COVID-19 was characterized by a higher concentration of anti-RBD IgA and IgG than the serum from the control group without COVID-19. No statistically significant difference was observed between the antibody levels in the serum samples obtained from symptomatic and asymptomatic women exposed to SARS-CoV-2 and between the antibody level and the time from a positive SARS-CoV-2 test result over the period studied.ConclusionOur results confirm the presence of SARS-CoV-2 IgA and IgG antibodies in the breastmilk of COVID-19 recovered women and the possibility of these antibodies in providing specific immunologic benefits to breastfeeding infants such as protection against the virus transmission and severity of the acquired COVID-19 disease.

Effects of Vaccination Against Influenza, Pertussis, and COVID-19 on Human Milk Antibodies: Current Evidence and Implications for Health Equity.

Human milk contains three antibody classes that confer mucosal immunity to the breastfed infant: secretory IgA (SIgA), secretory IgM (SIgM), and IgG. Influenza and pertussis vaccines administered during pregnancy induce pathogen specific SIgA and IgG responses in human milk that have been shown to protect the breastfed infant from these respiratory illnesses. In addition, mRNA vaccines against the SARS-CoV-2 virus administered during pregnancy and lactation induce anti-SARS-CoV-2 IgG and IgA responses in human milk. This review summarizes the immunologic benefits of influenza, pertussis, and COVID-19 vaccines conferred by human milk. Additionally, future research direction in human milk immunity and public health needs to improve lactational support are discussed.

Maternal Stress and Human Milk Antibodies During the COVID-19 Pandemic.

ImportanceSARS-CoV-2-specific antibodies in human milk might protect the breastfed infant against COVID-19. One of the factors that may influence human milk antibodies is psychological stress, which is suggested to be increased in lactating women during the COVID-19 pandemic.ObjectiveTo determine whether psychological stress is increased in lactating women during the COVID-19 pandemic, and if maternal stress is associated with the level of SARS-CoV-2-specific antibodies in human milk.DesignPopulation-based prospective cohort study.SettingData collection took place in the Netherlands between October 2020 and February 2021.ParticipantsLactating women living in the Netherlands were eligible to participate in this study. In total, 2310 women were included.ExposuresStress exposure during the COVID-19 pandemic was determined using the Perceived Stress Scale (PSS) questionnaire and maternal lifetime stress was determined by the Life Stressor Checklist – revised (LSC-r) questionnaire.Main Outcome(s) and Measure(s)Stress experience during the COVID-19 pandemic was compared with a pre-pandemic cohort. SARS-CoV-2-specific antibodies in human milk were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) with the Spike protein of SARS-CoV-2. The association between maternal stress and human milk antibodies was determined using a multiple regression model.ResultsThe PSS score of lactating mothers was not increased during the pandemic compared to the PSS score in the prepandemic cohort. Six hundred ninety-one participants had SARS-CoV-2-specific antibodies and were included in the regression models to assess the association between maternal stress and human milk antibodies. No association was found between PSS scores and human milk antibodies. In contrast, the LSC-r score was negatively associated with SARS-CoV-2-specific IgA in human milk (β = 0.98, 95% CI: 0.96–0.997, p = 0.03).Conclusions and RelevanceOur results suggest that lactating women in the Netherlands did not experience higher stress levels during the COVID-19 pandemic. Breastfed infants of mothers with high chronic stress levels receive lower amounts of antibodies through human milk, which possibly makes them more vulnerable to respiratory infections. This emphasizes the importance of psychological wellbeing during lactation.

Decreased Passive Immunity to Respiratory Viruses through Human Milk during the COVID-19 Pandemic.

ABSTRACTInfants may develop severe viral respiratory tract infections because their immune system is still developing in the first months after birth. Human milk provides passive humoral immunity during the first months of life. During the COVID-19 pandemic, circulation of common respiratory viruses was virtually absent due to the preventative measures resulting in reduced maternal exposure. Therefore, we hypothesized that this might result in lower antibody levels in human milk during the pandemic and, subsequently, decreased protection of infants against viral respiratory tract infections. We assessed antibody levels against respiratory syncytial virus (RSV), Influenza virus, and several seasonal coronaviruses in different periods of the COVID-19 pandemic in serum and human milk using a Luminex assay. IgG levels against RSV, Influenza, HCoV-OC43, HCoV-HKU1, and HCoV-NL63 in human milk were reduced with a factor of 1.7 (P < 0.001), 2.2 (P < 0.01), 2.6 (P < 0.05), 1.4 (P < 0.01), and 2.1 (P < 0.001), respectively, since the introduction of the COVID-19 restrictions. Furthermore, we observed that human milk of mothers that experienced COVID-19 contained increased levels of IgG and IgA binding to other respiratory viruses. Passive immunity via human milk against common respiratory viruses was reduced during the COVID-19 pandemic, which may have consequences for the protection of breastfed infants against respiratory infections.IMPORTANCE Passive immunity derived from antibodies in human milk is important for protecting young infants against invading viruses. During the COVID-19 pandemic, circulation of common respiratory viruses was virtually absent due to preventative measures. In this study, we observed a decrease in human milk antibody levels against common respiratory viruses several months into the COVID-19 pandemic. This waning of antibody levels might partially explain the previously observed surge of hospitalizations of infants, mostly due to RSV, when preventative hygiene measures were lifted. Knowledge of the association between preventative measures, antibody levels in human milk and subsequent passive immunity in infants might help predict infant hospital admissions and thereby enables anticipation to prevent capacity issues. Additionally, it is important in the consideration for strategies for future lockdowns to best prevent possible consequences for vulnerable infants.

Broad Cross-Reactive IgA and IgG against Human Coronaviruses in Milk Induced by COVID-19 Vaccination and Infection.

It is currently unclear if SARS-CoV-2 infection or mRNA vaccination can also induce IgG and IgA against common human coronaviruses (HCoVs) in lactating parents. Here we prospectively analyzed human milk (HM) and blood samples from lactating parents to measure the temporal patterns of anti-SARS-CoV-2 specific and anti-HCoV cross-reactive IgA and IgG responses. Two cohorts were analyzed: a vaccination cohort (n = 30) who received mRNA-based vaccines for COVID-19 (mRNA-1273 or BNT162b2), and an infection cohort (n = 45) with COVID-19 disease. Longitudinal HM and fingerstick blood samples were collected pre- and post-vaccination or, for infected subjects, at 5 time-points 14–28 days after confirmed diagnosis. The anti-spike(S) and anti-nucleocapsid(N) IgA and IgG antibody levels against SARS-CoV-2 and HCoVs were measured by multiplex immunoassay (mPlex-CoV). We found that vaccination significantly increased the anti-S IgA and IgG levels in HM. In contrast, while IgG levels increased after a second vaccine dose, blood and HM IgA started to decrease. Moreover, HM and blood anti-S IgG levels were significantly correlated, but anti-S IgA levels were not. SARS2 acute infection elicited anti-S IgG and IgA that showed much higher correlations between HM and blood compared to vaccination. Vaccination and infection were able to significantly increase the broadly cross-reactive IgG recognizing HCoVs in HM and blood than the IgA antibodies in HM and blood. In addition, the broader cross-reactivity of IgG in HM versus blood indicates that COVID-19 vaccination and infection might provide passive immunity through HM for the breastfed infants not only against SARS-CoV-2 but also against common cold coronaviruses.

Comparative Profiles of SARS-CoV-2 Spike-Specific Human Milk Antibodies Elicited by mRNA- and Adenovirus-Based COVID-19 Vaccines.

Background: Numerous COVID-19 vaccines are authorized globally. To date, ∼71% of doses comprise the Pfizer/BioNTech vaccine, and ∼17% the Moderna/NIH vaccine, both of which are messenger RNA (mRNA) based. The chimpanzee Ad-based Oxford/AstraZeneca (AZ) vaccine comprises ∼9%, while the Johnson & Johnson/Janssen (J&J) human adenovirus (Ad26) vaccine ranks fourth at ∼2%. No COVID-19 vaccine is yet available for children 0-4. One method to protect this population may be passive immunization through antibodies (Abs) provided in the milk of a lactating vaccinated person. Our early work and other reports have demonstrated that unlike the post-SARS-CoV-2 infection milk Ab profile, which is rich in specific secretory (s)IgA, the vaccine response is highly IgG dominant. Results: In this report, we present a comparative assessment of the milk Ab response elicited by Pfizer, Moderna, J&J, and AZ vaccines. This analysis revealed 86-100% of mRNA vaccine recipient milk exhibited Spike-specific IgG endpoint titers, which were 12- to 28-fold higher than those measured for Ad vaccine recipient milk. Ad-based vaccines elicited Spike-specific milk IgG in only 33-38% of recipients. Specific IgA was measured in 52-71% of mRNA vaccine recipient milk and 17-23% of Ad vaccine recipient milk. J&J recipient milk exhibited significantly lower IgA than Moderna recipients, and AZ recipients exhibited significantly lower IgA titers than Moderna and Pfizer. Less than 50% of milk of any group exhibited specific secretory Ab, with Moderna recipient IgA titers measuring significantly higher than AZ. Moderna appeared to most frequently elicit greater than twofold increases in specific secretory Ab titer relative to prevaccine sample. Conclusion: These data indicate that current Ad-based COVID-19 vaccines poorly elicit Spike-specific Ab in milk compared to mRNA-based vaccines, and that mRNA vaccines are preferred for immunizing the lactating population. This study highlights the need to design vaccines better aimed at eliciting an optimal milk Ab response.

Coronavirus Disease 2019 Vaccine Booster Effects Are Seen in Human Milk Antibody Response.

Infants remain at high risk for severe coronavirus disease 2019 (COVID-19). Human milk contains high levels of protective SARS CoV-2 specific antibodies post-infection and primary vaccine series, but levels decline over time. We hypothesized that the COVID-19 booster vaccine augment antibody production and the protection afforded to human milk-fed infants. We prospectively enrolled pregnant or lactating mothers planning to receive COVID-19 vaccination. We measured human milk IgG, IgA, and IgM antibodies targeting the SARS CoV-2 receptor binding domain within the spike protein and human milk neutralization activity against SARS CoV-2 in 10 lactating mothers from pre-COVID-19 primary series vaccine to post-booster dose. Human milk SARS CoV-2 specific IgG increased significantly from pre- to post-booster levels (median OD 0.33 vs. 2.02, P = 0.002). The IgG levels post-booster were even higher than the peak level after the primary series (2.02 vs. 0.95, P = 0.03). The increase in SARS CoV-2 specific IgA levels was not significant (0.10 vs. 0.33, P = 0.23). There was a strong correlation between paired maternal blood and milk IgG and IgA levels (IgG rho 0.52, P < 0.001, IgA rho 0.31, P = 0.05). Post-booster neutralizing activity was elevated compared to pre-booster levels (66% vs. 12% inhibition, P = 0.002). COVID-19 vaccine booster elicits SARS CoV-2 specific antibodies in human milk at higher levels compared to the initial primary series. This finding suggests that three doses of COVID-19 mRNA vaccination leads to improved mucosal response in human milk and reinforces current guidance recommending all pregnant or lactating mothers receive full COVID-19 vaccine courses with a booster dose.

Review of Increase in SARS-CoV-2 RBD-specific IgA and IgG Antibodies in Human Milk from Lactating Women Following the COVID-19 Booster Vaccination

Review of Increase in SARS-CoV-2 RBD-specific IgA and IgG Antibodies in Human Milk from Lactating Women Following the COVID-19 Booster Vaccination

Restricting Cow's Milk in the Maternal Diet Reduces the Titers of β-Lactoglobulin-Specific IgG Antibodies in Human Milk.

Background: Human milk antibodies specific to allergen enhance immunological tolerance in neonates by educating their immature mucosal immunity. The impact of restricting food allergens in diet and maternal factors on the levels of allergen-specific antibodies in human milk remains unclear. We aimed to evaluate the influence of the maternal avoidance diet of cow's milk on the titers of IgG, SIgA/IgA, and IgM specific to β-lactoglobulin (BLG) in human milk. Materials and Methods: Human milk samples were collected from 26 women nonrestricting cow's milk and 11 women restricting cow's milk. The titers of IgG, SIgA/IgA, and SIgM/IgM specific to BLG were measured using ELISA. Results: BLG-specific IgG titers were 2.9-fold higher in women nonrestricting cow's milk than those restricting cow's milk in their diet (p = 0.026), but BLG-specific SIgA/IgA and SIgM/IgM titers were comparable between these two groups. BLG-specific IgG was positively correlated with BLG-specific SIgA/IgA titers in milk from mothers nonrestricting cow's milk (p = 0.0007) but did not correlate for mothers restricting cow's milk. BLG-specific SIgA/IgA titer decreased with increasing postpartum time in milk from women restricting cow's milk (p = 0.019). Type of delivery, infant gender, maternal age, and probiotic intake did not influence the BLG-specific antibody titers. Conclusions: This study reveals that the secretion of BLG-specific IgG in human milk increases in women nonrestricting cow's milk compared with women restricting cow's milk. The role of breast milk allergen-specific antibodies on the neonatal gut (crosstalk with immune and epithelial cells) remains to be investigated.

The IgA in milk induced by SARS-CoV-2 infection is comprised of mainly secretory antibody that is neutralizing and highly durable over time

Approximately 10% of infants infected with SARS-CoV-2 will experience COVID-19 illness requiring advanced care. A potential mechanism to protect this population is passive immunization via the milk of a previously infected person. We and others have reported on the presence of SARS-CoV-2-specific antibodies in human milk. We now report the prevalence of SARS-CoV-2 IgA in the milk of 74 COVID-19-recovered participants, and find that 89% of samples are positive for Spike-specific IgA. In a subset of these samples, 95% exhibited robust IgA activity as determined by endpoint binding titer, with 50% considered high-titer. These IgA-positive samples were also positive for Spike-specific secretory antibody. Levels of IgA antibodies and secretory antibodies were shown to be strongly positively correlated. The secretory IgA response was dominant among the milk samples tested compared to the IgG response, which was present in 75% of samples and found to be of high-titer in only 13% of cases. Our IgA durability analysis using 28 paired samples, obtained 4-6 weeks and 4-10 months after infection, found that all samples exhibited persistently significant Spike-specific IgA, with 43% of donors exhibiting increasing IgA titers over time. Finally, COVID-19 and pre-pandemic control milk samples were tested for the presence of neutralizing antibodies; 6 of 8 COVID-19 samples exhibited neutralization of Spike-pseudotyped VSV (IC50 range, 2.39-89.4ug/mL) compared to 1 of 8 controls. IgA binding and neutralization capacities were found to be strongly positively correlated. These data are highly relevant to public health, not only in terms of the protective capacity of these antibodies for breastfed infants, but also for the potential use of such antibodies as a COVID-19 therapeutic, given that secretory IgA is highly in all mucosal compartments.