Milk Secretory IgA Related to Shigella Virulence Antigens

Abstract

It has long been suggested that breastfeeding has a protective effect against shigellosis both in terms of decreasing the frequency of disease and lessening the severity in those infants who acquired infection. Antibodies have been demonstrated in milk directed toward the lipopolysaccharide (LPS) antigens of Shigella. However, the four species include a large number of antigenically distinct LPS types (S. dysenteriae [serogroup A] twelve unrelated LPS types, S. flexneri [serogroup B] six serotypes, S. boydii [serogroup C] eighteen immunologically unrelated LPS types, and S. sonnei [serogroup D] one LPS type). For human milk to provide protection against shigellosis on the basis of antibodies against LPS, a very large repertoire of serotype specific antibodies might be required. Although the LPS antigens of Shigella are not generally closely related, these organisms do share a common virulence mechanism. Virulence in Shigellae is a complex phenomenon depending on both chromosomal and plasmid coded loci working in concert to produce multiple virulence enhancing factors (Fig. 1). The most important of these factors, those responsible for invasion of mammalian cells, are encoded on a 30–37 kb segment of the large plasmid that is similar in all Shigellae. This plasmid encodes for production of a group of immunodominant proteins, the invasion plasmid antigens A (ipaA), B (ipaB), C (ipaC), and D (ipaD), that are genetically and immunologically identical or nearly identical in all of these organisms. Because these ipa proteins represent the shared molecular basis for Shigella virulence, we sought to demonstrate whether antibodies to these determinants might be present in human milk. We compared milk samples from two populations of women with differing Shigella exposure risk: one with a high frequency of shigellosis (Mexican women) and the other with a lower frequency (US women).