Browsing by Subject "Milk, Human"
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Item Unknown Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.(J Virol, 2015-10) Pollara, Justin; McGuire, Erin; Fouda, Genevieve G; Rountree, Wes; Eudailey, Josh; Overman, R Glenn; Seaton, Kelly E; Deal, Aaron; Edwards, R Whitney; Tegha, Gerald; Kamwendo, Deborah; Kumwenda, Jacob; Nelson, Julie AE; Liao, Hua-Xin; Brinkley, Christie; Denny, Thomas N; Ochsenbauer, Christina; Ellington, Sascha; King, Caroline C; Jamieson, Denise J; van der Horst, Charles; Kourtis, Athena P; Tomaras, Georgia D; Ferrari, Guido; Permar, Sallie RUNLABELLED: Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response. IMPORTANCE: Infants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1-transmitting and -nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope proteins were associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding and the development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation.Item Unknown Beverage Consumption Patterns among Infants and Young Children (0⁻47.9 Months): Data from the Feeding Infants and Toddlers Study, 2016.(Nutrients, 2018-06-26) Kay, Melissa C; Welker, Emily B; Jacquier, Emma F; Story, Mary T(1) Background: Data about early life beverage intake patterns is sparse. We describe beverage patterns among infants and young children from the Feeding Infants and Toddlers Study (FITS) 2016. (2) Methods: FITS 2016 is a cross-sectional survey of U.S. parents/caregivers of children 0⁻47.9 months (n = 3235). Food and beverage intakes were collected by 24-h dietary recalls to describe beverage consumption patterns including: a) prevalence of consumption, per capita and per consumer intake, b) contribution to intake of calories and key nutrients, and c) prevalence according to eating occasions. (3) Results: Breast milk and infant formula were commonly consumed among <12-month-olds. Among 12⁻23.9-month-olds, the most commonly consumed beverage was whole milk (67% consuming), followed by 100% juice (50% consuming). Plain drinking water was consumed by 70% of 12⁻23.9-month-olds and 78% of 24⁻47.9-month-olds. Among 12⁻47.9-month-olds, milks provided more energy and key nutrients than all other beverages. Across eating occasions, sugar-sweetened beverage (SSB) consumption, especially in the form of fruit-flavored drinks, was higher among 24⁻47.9 compared to 12⁻23.9-month-olds. Only 23⁻32% of ≥12-month-olds consumed milk or water at lunch or dinner. (4) Conclusions: Opportunities exist to improve beverage patterns. Future interventions may benefit from focusing on timely introduction of age-appropriate beverages and reducing consumption of SSBs.Item Unknown HIV-specific functional antibody responses in breast milk mirror those in plasma and are primarily mediated by IgG antibodies.(J Virol, 2011-09) Fouda, GG; Yates, NL; Pollara, J; Shen, X; Overman, GR; Mahlokozera, T; Wilks, AB; Kang, HH; Salazar-Gonzalez, JF; Salazar, MG; Kalilani, L; Meshnick, SR; Hahn, BH; Shaw, GM; Lovingood, RV; Denny, TN; Haynes, B; Letvin, NL; Ferrari, G; Montefiori, DC; Tomaras, GD; Permar, SR; Immunology, the Center for HIVAIDS VaccineDespite months of mucosal virus exposure, the majority of breastfed infants born to HIV-infected mothers do not become infected, raising the possibility that immune factors in milk inhibit mucosal transmission of HIV. HIV Envelope (Env)-specific antibodies are present in the milk of HIV-infected mothers, but little is known about their virus-specific functions. In this study, HIV Env-specific antibody binding, autologous and heterologous virus neutralization, and antibody-dependent cell cytotoxicity (ADCC) responses were measured in the milk and plasma of 41 HIV-infected lactating women. Although IgA is the predominant antibody isotype in milk, HIV Env-specific IgG responses were higher in magnitude than HIV Env-specific IgA responses in milk. The concentrations of anti-HIV gp120 IgG in milk and plasma were directly correlated (r = 0.75; P < 0.0001), yet the response in milk was 2 logarithm units lower than in plasma. Similarly, heterologous virus neutralization (r = 0.39; P = 0.010) and ADCC activity (r = 0.64; P < 0.0001) in milk were directly correlated with that in the systemic compartment but were 2 log units lower in magnitude. Autologous neutralization was rarely detected in milk. Milk heterologous virus neutralization titers correlated with HIV gp120 Env-binding IgG responses but not with IgA responses (r = 0.71 and P < 0.0001, and r = 0.17 and P = 0.30). Moreover, IgGs purified from milk and plasma had equal neutralizing potencies against a tier 1 virus (r = 0.65; P < 0.0001), whereas only 1 out of 35 tested non-IgG milk fractions had detectable neutralization. These results suggest that plasma-derived IgG antibodies mediate the majority of the low-level HIV neutralization and ADCC activity in breast milk.Item Unknown Human milk sharing practices in the U.S.(Maternal & child nutrition, 2016-04) Palmquist, Aunchalee EL; Doehler, KirstenThe primary objective of this study is to describe human milk sharing practices in the U.S. Specifically, we examine milk sharing social networks, donor compensation, the prevalence of anonymous milk sharing interactions, recipients' concerns about specific milk sharing risks, and lay screening behaviors. Data on human milk sharing practices were collected via an online survey September 2013-March 2014. Chi-square analyses were used to test the association between risk perception and screening practices. A total of 867 (661 donors, 206 recipients) respondents were included in the analyses. Most (96.1%) reported sharing milk face-to-face. Only 10% of respondents reported giving or receiving milk through a non-profit human milk bank, respectively. There were no reports of anonymous purchases of human milk. A small proportion of recipients (4.0%) reported that their infant had a serious medical condition. Screening of prospective donors was common (90.7%) but varied with social relationship and familiarity. Likewise, concern about specific milk sharing risks was varied, and risk perception was significantly associated (P-values = 0.01 or less) with donor screening for all risk variables except diet. Understanding lay perceptions of milk sharing risk and risk reduction strategies that parents are using is an essential first step in developing public health interventions and clinical practices that promote infant safety.Item Unknown Lack of B cell dysfunction is associated with functional, gp120-dominant antibody responses in breast milk of simian immunodeficiency virus-infected African green monkeys.(J Virol, 2013-10) Amos, Joshua D; Wilks, Andrew B; Fouda, Genevieve G; Smith, Shannon D; Colvin, Lisa; Mahlokozera, Tatenda; Ho, Carrie; Beck, Krista; Overman, R Glenn; DeMarco, C Todd; Hodge, Terry L; LaBranche, Celia C; Montefiori, David C; Denny, Thomas N; Liao, Hua-Xin; Tomaras, Georgia D; Moody, M Anthony; Permar, Sallie RThe design of an effective vaccine to reduce the incidence of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) via breastfeeding will require identification of protective immune responses that block postnatal virus acquisition. Natural hosts of simian immunodeficiency virus (SIV) sustain nonpathogenic infection and rarely transmit the virus to their infants despite high milk virus RNA loads. This is in contrast to HIV-infected women and SIV-infected rhesus macaques (RhMs), nonnatural hosts which exhibit higher rates of postnatal virus transmission. In this study, we compared the systemic and mucosal B cell responses of lactating, SIV-infected African green monkeys (AGMs), a natural host species, to that of SIV-infected RhMs and HIV-infected women. AGMs did not demonstrate hypergammaglobulinemia or accumulate circulating memory B cells during chronic SIV infection. Moreover, the milk of SIV-infected AGMs contained higher proportions of naive B cells than RhMs. Interestingly, AGMs exhibited robust milk and plasma Env binding antibody responses that were one to two logs higher than those in RhMs and humans and demonstrated autologous neutralizing responses in milk at 1 year postinfection. Furthermore, the plasma and milk Env gp120-binding antibody responses were equivalent to or predominant over Env gp140-binding antibody responses in AGMs, in contrast to that in RhMs and humans. The strong gp120-specific, functional antibody responses in the milk of SIV-infected AGMs may contribute to the rarity of postnatal transmission observed in natural SIV hosts.Item Unknown Origin and evolution of HIV-1 in breast milk determined by single-genome amplification and sequencing.(J Virol, 2011-03) Salazar-Gonzalez, JF; Salazar, MG; Learn, GH; Fouda, GG; Kang, HH; Mahlokozera, T; Wilks, AB; Lovingood, RV; Stacey, A; Kalilani, L; Meshnick, SR; Borrow, P; Montefiori, DC; Denny, TN; Letvin, NL; Shaw, GM; Hahn, BH; Permar, SR; A0167854, Center for HIV AIDS Vaccine ImmunologyHIV transmission via breastfeeding accounts for a considerable proportion of infant HIV acquisition. However, the origin and evolution of the virus population in breast milk, the likely reservoir of transmitted virus variants, are not well characterized. In this study, HIV envelope (env) genes were sequenced from virus variants amplified by single-genome amplification from plasmas and milk of 12 chronically HIV-infected, lactating Malawian women. Maximum likelihood trees and statistical tests of compartmentalization revealed interspersion of plasma and milk HIV env sequences in the majority of subjects, indicating limited or no compartmentalization of milk virus variants. However, phylogenetic tree analysis further revealed monotypic virus variants that were significantly more frequent in milk (median proportion of identical viruses, 29.5%; range, 0 to 61%) than in plasma (median proportion of identical viruses, 0%; range, 0 to 26%) (P = 0.002), suggesting local virus replication in the breast milk compartment. Moreover, clonally amplified virus env genes in milk produced functional virus Envs that were all CCR5 tropic. Milk and plasma virus Envs had similar predicted phenotypes and neutralization sensitivities to broadly neutralizing antibodies in both transmitting and nontransmitting mothers. Finally, phylogenetic comparison of longitudinal milk and plasma virus env sequences revealed synchronous virus evolution and new clonal amplification of evolved virus env genes in milk. The limited compartmentalization and the clonal amplification of evolving, functional viruses in milk indicate continual seeding of the mammary gland by blood virus variants, followed by transient local replication of these variants in the breast milk compartment.Item Unknown Postnatal cytomegalovirus exposure in infants of antiretroviral-treated and untreated HIV-infected mothers.(Infect Dis Obstet Gynecol, 2014) Meyer, Sarah A; Westreich, Daniel J; Patel, Emily; Ehlinger, Elizabeth P; Kalilani, Linda; Lovingood, Rachel V; Denny, Thomas N; Swamy, Geeta K; Permar, Sallie RHIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV transmission may impact growth and disease progression in HIV-exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA load and postnatal transmission, its impact on milk CMV load is unclear. We examined the relationship between milk CMV and HIV-1 load (4-6 weeks postpartum) and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian women and assessed the relationship between milk CMV load and postnatal growth in HIV-exposed, breastfed infants through six months of age. Despite an association between milk HIV-1 RNA and CMV DNA load (0.39 log(10) rise CMV load per log(10) rise HIV-1 RNA load, 95% CI 0.13-0.66), milk CMV load was similar in antiretroviral-treated and untreated women. Higher milk CMV load was associated with lower length-for-age (-0.53, 95% CI: -0.96, -0.10) and weight-for-age (-0.40, 95% CI: -0.67, -0.13) Z-score at six months in exposed, uninfected infants. As the impact of maternal antiretroviral therapy on the magnitude of postnatal CMV exposure may be limited, our findings of an inverse relationship between infant growth and milk CMV load highlight the importance of defining the role of perinatal CMV exposure on growth faltering of HIV-exposed infants.Item Unknown Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants.(Retrovirology, 2013-01-10) Fouda, Genevieve G; Mahlokozera, Tatenda; Salazar-Gonzalez, Jesus F; Salazar, Maria G; Learn, Gerald; Kumar, Surender B; Dennison, S Moses; Russell, Elizabeth; Rizzolo, Katherine; Jaeger, Frederick; Cai, Fangping; Vandergrift, Nathan A; Gao, Feng; Hahn, Beatrice; Shaw, George M; Ochsenbauer, Christina; Swanstrom, Ronald; Meshnick, Steve; Mwapasa, Victor; Kalilani, Linda; Fiscus, Susan; Montefiori, David; Haynes, Barton; Kwiek, Jesse; Alam, S Munir; Permar, Sallie RBACKGROUND: Breastfeeding is a leading cause of infant HIV-1 infection in the developing world, yet only a minority of infants exposed to HIV-1 via breastfeeding become infected. As a genetic bottleneck severely restricts the number of postnatally-transmitted variants, genetic or phenotypic properties of the virus Envelope (Env) could be important for the establishment of infant infection. We examined the efficiency of virologic functions required for initiation of infection in the gastrointestinal tract and the neutralization sensitivity of HIV-1 Env variants isolated from milk of three postnatally-transmitting mothers (n = 13 viruses), five clinically-matched nontransmitting mothers (n = 16 viruses), and seven postnatally-infected infants (n = 7 postnatally-transmitted/founder (T/F) viruses). RESULTS: There was no difference in the efficiency of epithelial cell interactions between Env virus variants from the breast milk of transmitting and nontransmitting mothers. Moreover, there was similar efficiency of DC-mediated trans-infection, CCR5-usage, target cell fusion, and infectivity between HIV-1 Env-pseudoviruses from nontransmitting mothers and postnatal T/F viruses. Milk Env-pseudoviruses were generally sensitive to neutralization by autologous maternal plasma and resistant to breast milk neutralization. Infant T/F Env-pseudoviruses were equally sensitive to neutralization by broadly-neutralizing monoclonal and polyclonal antibodies as compared to nontransmitted breast milk Env variants. CONCLUSION: Postnatally-T/F Env variants do not appear to possess a superior ability to interact with and cross a mucosal barrier or an exceptional resistance to neutralization that define their capability to initiate infection across the infant gastrointestinal tract in the setting of preexisting maternal antibodies.Item Unknown Tenascin-C is an innate broad-spectrum, HIV-1-neutralizing protein in breast milk.(Proceedings of the National Academy of Sciences of the United States of America, 2013-11) Fouda, Genevieve G; Jaeger, Frederick H; Amos, Joshua D; Ho, Carrie; Kunz, Erika L; Anasti, Kara; Stamper, Lisa W; Liebl, Brooke E; Barbas, Kimberly H; Ohashi, Tomoo; Moseley, Martin Arthur; Liao, Hua-Xin; Erickson, Harold P; Alam, S Munir; Permar, Sallie RAchieving an AIDS-free generation will require elimination of postnatal transmission of HIV-1 while maintaining the nutritional and immunologic benefits of breastfeeding for infants in developing regions. Maternal/infant antiretroviral prophylaxis can reduce postnatal HIV-1 transmission, yet toxicities and the development of drug-resistant viral strains may limit the effectiveness of this strategy. Interestingly, in the absence of antiretroviral prophylaxis, greater than 90% of infants exposed to HIV-1 via breastfeeding remain uninfected, despite daily mucosal exposure to the virus for up to 2 y. Moreover, milk of uninfected women inherently neutralizes HIV-1 and prevents virus transmission in animal models, yet the factor(s) responsible for this anti-HIV activity is not well-defined. In this report, we identify a primary HIV-1-neutralizing protein in breast milk, Tenascin-C (TNC). TNC is an extracellular matrix protein important in fetal development and wound healing, yet its antimicrobial properties have not previously been established. Purified TNC captured and neutralized multiclade chronic and transmitted/founder HIV-1 variants, and depletion of TNC abolished the HIV-1-neutralizing activity of milk. TNC bound the HIV-1 Envelope protein at a site that is induced upon engagement of its primary receptor, CD4, and is blocked by V3 loop- (19B and F39F) and chemokine coreceptor binding site-directed (17B) monoclonal antibodies. Our results demonstrate the ability of an innate mucosal host protein found in milk to neutralize HIV-1 via binding to the chemokine coreceptor site, potentially explaining why the majority of HIV-1-exposed breastfed infants are protected against mucosal HIV-1 transmission.Item Unknown The magnitude and kinetics of the mucosal HIV-specific CD8+ T lymphocyte response and virus RNA load in breast milk.(PLoS One, 2011) Mahlokozera, T; Kang, HH; Goonetilleke, N; Stacey, AR; Lovingood, RV; Denny, TN; Kalilani, L; Bunn, JE; Meshnick, SR; Borrow, P; Letvin, NL; Permar, SR; Immunology, Center for HIVAIDS VaccineBACKGROUND: The risk of postnatal HIV transmission is associated with the magnitude of the milk virus load. While HIV-specific cellular immune responses control systemic virus load and are detectable in milk, the contribution of these responses to the control of virus load in milk is unknown. METHODS: We assessed the magnitude of the immunodominant GagRY11 and subdominant EnvKY9-specific CD8+ T lymphocyte response in blood and milk of 10 A*3002+, HIV-infected Malawian women throughout the period of lactation and correlated this response to milk virus RNA load and markers of breast inflammation. RESULTS: The magnitude and kinetics of the HIV-specific CD8+ T lymphocyte responses were discordant in blood and milk of the right and left breast, indicating independent regulation of these responses in each breast. However, there was no correlation between the magnitude of the HIV-specific CD8+ T lymphocyte response and the milk virus RNA load. Further, there was no correlation between the magnitude of this response and markers of breast inflammation. CONCLUSIONS: The magnitude of the HIV-specific CD8+ T lymphocyte response in milk does not appear to be solely determined by the milk virus RNA load and is likely only one of the factors contributing to maintenance of low virus load in milk.Item Unknown Transient compartmentalization of simian immunodeficiency virus variants in the breast milk of african green monkeys.(J Virol, 2013-10) Ho, Carrie; Wu, Steven; Amos, Joshua D; Colvin, Lisa; Smith, Shannon D; Wilks, Andrew B; Demarco, C Todd; Brinkley, Christie; Denny, Thomas N; Schmitz, Joern E; Rodrigo, Allen G; Permar, Sallie RNatural hosts of simian immunodeficiency virus (SIV), African green monkeys (AGMs), rarely transmit SIV via breast-feeding. In order to examine the genetic diversity of breast milk SIV variants in this limited-transmission setting, we performed phylogenetic analysis on envelope sequences of milk and plasma SIV variants of AGMs. Low-diversity milk virus populations were compartmentalized from that in plasma. However, this compartmentalization was transient, as the milk virus lineages did not persist longitudinally.Item Unknown When separation is not the answer: Breastfeeding mothers and infants affected by COVID-19.(Maternal & child nutrition, 2020-10) Tomori, Cecília; Gribble, Karleen; Palmquist, Aunchalee EL; Ververs, Mija-Tesse; Gross, Marielle SThe World Health Organization (WHO) has provided detailed guidance on the care of infants of women who are persons under investigation (PUI) or confirmed to have COVID-19. The guidance supports immediate post-partum mother-infant contact and breastfeeding with appropriate respiratory precautions. Although many countries have followed WHO guidance, others have implemented infection prevention and control (IPC) policies that impose varying levels of post-partum separation and discourage or prohibit breastfeeding or provision of expressed breast milk. These policies aim to protect infants from the potential harm of infection from their mothers, yet they may fail to fully account for the impact of separation. Global COVID-19 data are suggestive of potentially lower susceptibility and a typically milder course of disease among children, although the potential for severe disease in infancy remains. Separation causes cumulative harms, including disrupting breastfeeding and limiting its protection against infectious disease, which has disproportionate impacts on vulnerable infants. Separation also presumes the replaceability of breastfeeding-a risk that is magnified in emergencies. Moreover, separation does not ensure lower viral exposure during hospitalizations and post-discharge, and contributes to the burden on overwhelmed health systems. Finally, separation magnifies maternal health consequences of insufficient breastfeeding and compounds trauma in communities who have experienced long-standing inequities and violence, including family separation. Taken together, separating PUI/confirmed SARS-CoV-2-positive mothers and their infants may lead to excess preventable illnesses and deaths among infants and women around the world. Health services must consider the short-andlong-term impacts of separating mothers and infants in their policies.