Breast Milk: Proactive Immunomodulation and Mucosal Protection Against Viruses and Other Pathogens

Chiara Cerini; Grace M Aldrovandi

Disclosures

Future Virology. 2013;8(11):1127-1134. 

In This Article

Maternal Immunization

Maternal immunization (before or during pregnancy, or immediately after delivery – known as the 'cocoon effect') has emerged as a simple, safe and cost-effective strategy to protect the neonate against illness, bypassing the well-known immunological obstacles associated with neonatal vaccination. This approach has been extremely successful in efforts to eliminate neonatal tetanus and is even being advocated as a strategy for the control of infant pertussis, influenza and other diseases.[67–69]

Most maternal vaccination strategies have focused on antenatal immunization, relying on effective transplacental antibody transfer and persistence of maternal antibodies in the infant for approximately 2 months. However, protective levels of maternal antibodies differ widely depending on initial levels, specificity and avidity.[70] For some diseases the levels of specific antibodies required for protection are not known (i.e., for pertussis). Interestingly, antenatal maternal vaccination appears to positively influence the production of specific antibodies transferred to the infant via breast milk for at least 5–6 months postpartum.[71–73] Assessing the amount of pneumococcal antibody transmitted to the infants after maternal pneumococcal immunization, Shahid et al. found that the half-life of the breast milk IgA for some serotypes (19F) were significantly higher in vaccine recipients up to 5 months after delivery.[71]

Deubzer et al. documented that maternal vaccination with polyvalent pneumococcal polysaccharide vaccine boosts the capacity of colostrum to inhibit the adherence of pneumococci to pharyngeal epithelial cells.[74] In a randomized, placebo-controlled trial during the RSV season, higher vaccine-specific anti-F IgA and IgG concentrations in breast milk were found in mothers who received the anti-RSV PFP-2 vaccine.[75]

These observations may be of greater importance in preterm babies, who receive less transplacentally acquired immunoglobulin. Interestingly, Mother Nature may have already accounted for this deficiency, as higher concentrations of sIgA are found in the breast milk of mothers who deliver preterm infants.[76] The implications for these differences on vaccine strategies remain to be elucidated.

Although data on postnatal maternal immunization are sparse, it appears to be beneficial. A randomized, placebo-controlled trial of 23-valent pneumococcal polysaccharide immunization in Papua New Guinea reported a nonsignificant decrease in the number of acute lower respiratory tract illness over a 3-year period in children whose mothers were vaccinated antepartum (78.5% in children whose mothers had received placebo vs 67.8% in children whose mothers had received vaccine; p = 0.1). However, among infants who were 1–17 months of age at the time of maternal immunization, there was a significant reduction in acute lower respiratory tract illness episodes over that same period (91.6% in placebo vs 76.2% in the vaccine arm; p = 0.02).[66] A significant transfer of pertussis antigen-specific IgA to breast milk in vaccinated postpartum mothers has also been documented.[77]

While maternal vaccination may substantially improve child health, it also poses challenges, including blunting of the infant's responses to her/his own vaccinations due to passively acquired maternal antibodies.[78] Lower seroconversion rates and antibody levels were first described for the measles vaccine[79] and have been observed with other vaccines.[80–82] However, these suppressive effects are highly variable and inconsistent not only between vaccines, but also for the same vaccine in different studies. Dose of vaccine and route of administration appear to be key factors in mediating the effect of transplacental maternal antibodies on infant vaccine response. Interestingly, blunting of infant antibody response does not appear to inhibit infant T-cell responses and/or infant priming.[83–86] T-cell priming in the presence of maternal antibodies has been associated with boosted high avidity antibody responses when the infant is subsequently challenged. Given the importance of T-cell responses that can be induced by a vaccine, particularly against viral pathogens, the significance of lower antibody levels is uncertain. In addition, how postpartum immunization and breast milk-mediated protection would impact infant immune response to vaccination remains largely unexplored.

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