Significance Achieving an AIDS-free generation will require elimination of breast milk transmission of HIV-1, as breastfeeding is a cornerstone of infant survival in developing regions. Antiretroviral prophylaxis considerably reduces postnatal HIV-1 transmission, yet its efficacy is limited by access, adherence, toxicities, and resistance of maternal HIV-1 strains. Alternative, safe strategies of impeding postnatal HIV-1 transmission will be required to eliminate infant HIV-1 infection. In this paper, we identify an innate HIV-neutralizing protein in breast milk, Tenascin-C, which captures and neutralizes HIV-1 virions via binding to the chemokine coreceptor binding site on the HIV-1 Envelope. This protein has the potential to be developed as a prevention strategy for postnatal and other modes of HIV-1 transmission.

Similar immunologic parameters in milk of CMV-seropositive mothers of VLBW infants with and without symptomatic postnatal CMV infection indicate that screening milk by these parameters may not predict disease risk. However, the inverse correlation between milk CMV IgG avidity and CMV load may suggest that enhancement of maternal CMV-specific IgG responses could aid in reduction of CMV shedding into breast milk.

Tenascin-C (TNC) is a newly identified innate HIV-1-neutralizing protein present in breast milk, yet its presence and potential HIV-inhibitory function in other mucosal fluids is unknown. In this study, we identified TNC as a component of semen and cervical fluid of HIV-1-infected and uninfected individuals, although it is present at a significantly lower concentration and frequency compared to that of colostrum and mature breast milk, potentially due to genital fluid protease degradation. However, TNC was able to neutralize HIV-1 after exposure to low pH, suggesting that TNC could be active at low pH in the vaginal compartment. As mucosal fluids are complex and contain a number of proteins known to interact with the HIV-1 envelope, we further studied the relationship between the concentration of TNC and neutralizing activity in breast milk. The amount of TNC correlated only weakly with the overall innate HIV-1-neutralizing activity of breast milk of uninfected women and negatively correlated with neutralizing activity in milk of HIV-1 infected women, indicating that the amount of TNC in mucosal fluids is not adequate to impede HIV-1 transmission. Moreover, the presence of polyclonal IgG from milk of HIV-1 infected women, but not other HIV-1 envelope-binding milk proteins or monoclonal antibodies, blocked the neutralizing activity of TNC. Finally, as exogenous administration of TNC would be necessary for it to mediate measurable HIV-1 neutralizing activity in mucosal compartments, we established that recombinantly produced TNC has neutralizing activity against transmitted/founder HIV-1 strains that mimic that of purified TNC. Thus, we conclude that endogenous TNC concentration in mucosal fluids is likely inadequate to block HIV-1 transmission to uninfected individuals.

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BackgroundInfants with chylothorax after congenital heart disease surgery are commonly treated using modified‐fat breast milk. The effect of fat removal on breast milk macronutrients remains unclear. We compared macronutrient content of breast milk with breast milk skimmed using 3 methods, including a novel device, a cream separator.MethodsThawed frozen breast milk samples from 30 women were defatted using refrigerated centrifuge, cream separator, and manual separation after refrigeration. We used standard assays to measure energy, protein, and fat content of breast milk samples.ResultsAll fat removal methods yielded skimmed breast milk with substantially lower fat and energy content. Mean energy content in breast milk skimmed by centrifuge (36.7 [SD 3.6] kcal/100 mL) was similar to that from cream separator (38.8 [3.5] kcal/100 mL). Both centrifuge and cream separator methods removed almost all fat and substantially more fat than the manual fat removal method. For unprocessed milk, energy and fat content estimated by creamatocrit was similar to reference method measurements; in skimmed milk, the creamatocrit significantly overestimated fat content. Mean protein content of skimmed breast milk was similar to unprocessed breast milk (mean 1.25 [0.31] g/100 mL).ConclusionBreast milk fat removal did not significantly alter protein levels. In skimmed breast milk, the overestimation of fat content using creamatocrit method suggests a need for more accurate bedside methods to assess macronutrient content. The similar macronutrient composition of breast milk skimmed by cream separator and centrifuge suggests the potential for cream separator use as a new, portable defatting method for hospitals and families.