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

Chiara Cerini; Grace M Aldrovandi


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

In This Article

Abstract and Introduction


The majority of microorganisms infecting humans cross through the mucosal barrier. This is particularly true in infants who explore the world with their mouths while their immune system is still developing. Human milk not only supplies the nutritional needs of the newborn and protects the baby against infection by confering trophic protection to the intestinal mucosa, but additionally shapes the infant's gut microbiota and instructs immunomodulation. Reflecting maternal environmental exposition and in virtue of its multiple mechanism of action, secretory IgA in milk exerts a decisive role in direct and cross-protection against a variety of pathogens. Its active role in priming the infant's immune system is an intriguing hypothesis. From this perspective, breast milk antibodies produced by means of maternal immunization might represent protective and proactive factors able to shape and enhance the infant's immune responses. Strategies to optimize the benefits of maternal immunization include novel vaccine formulations and mucosal route of delivery.


One of the key determinants of a successful pregnancy is mutual fetal and maternal immune tolerance. After birth, infant survival depends on transitioning from a tolerogenic state to a phase of immune activation, while both systemic and secretory immune functions mature.[1] During this period, infants are extremely vulnerable to infections and often have suboptimal responses to vaccination. Therefore, infants rely on maternal immune protection through antibodies initially acquired transplacentally and subsequently via breast milk.

Evolutionary biologists hypothesize that lactation evolved over 200 million years to provide infants with both immunologic and nutritional support.[2] This rich secretion contains antimicrobial, anti-inflammatory and immunomodulatory factors that serve to compensate for many aspects of the infant's functional immune immaturity.[3]

These developmental immune deficiencies include quantitative and qualitative delays in antibody production, suboptimal T-cell immunity, phagocytic function and complement cascade activation (reviewed in[4,5]). The immunologic benefit of breastfeeding is 'dose' dependent – that is, the benefit is proportional to the degree of its duration and exclusivity.[4] Exclusive breastfeeding refers to the practice of providing no other liquids or solid food to the infant – not even water – with the exception of oral rehydration solution, or drops/syrups of vitamins, minerals or medicines.[6] Although the protective effects of breastfeeding are most readily demonstrable in populations living in developing countries – where not only access to vaccines and healthcare, but also to potable water is scarce – several good-quality studies in industrialized countries have noted significant reductions in common infectious diseases of infancy (otitis media, respiratory tract diseases and nonspecific gastrointestinal infections) in breastfed infants. In addition, breastfeeding also has profound effects on the maturation and development of the infant's intestine and his/her systemic immunity.[5]

Infants are born with an essentially sterile intestinal tract, and over the course of the first 3 years of life environmental factors determine the colonizing organisms.[7] It has long been recognized that the stools of breastfed infants are distinct from those of formula-fed infants.[7] Emerging data on the critical role of the microbiota in immunity strongly suggest that these differences in the microbial composition may be responsible for the differences in autoimmunity and other diseases observed between breastfed and formula-fed infants.[8–12]

In this paper, we will review factors in breast milk that mediate infant protection from viral and other microbial pathogens. Additionally, we will discuss maternal immunization as a strategy to protect infants.