Norovirus-specific immunoglobulin A in breast milk for protection against norovirus-associated diarrhea among infants

概要

Background: Norovirus (NV) causes acute gastroenteritis in infants. Humoral and fecal immunoglobulin A (IgA) responses have been correlated with protection against NV; however, the role of breast milk IgA against NV infection and associated diarrhea is still unknown. This study aimed to evaluate the protective role of NV-specific IgA (NV-IgA) in breast milk.

Methods: Ninety-five breast milk samples collected from mothers enrolled in a 2016–2017 Peruvian birth cohort study were tested for total IgA and NV-IgA by ELISA using GII·4 variants and non-GII·4 genotype virus-like particles (VLPs). Breast milk samples were grouped according to the NV infection and diarrheal status of infants: NV positive with diarrhea (NV+D+, n=18); NV positive without diarrhea (NV+D-, n=37); and NV negative without diarrhea (NV-D-, n=40). The percent positivity and titer of NV-IgA were compared among groups. Cross-reactivity was estimated based on the correlation of ratio between NV-IgA against GII·4 variants and non-GII·4 genotype VLPs.

Results: NV-IgA had high positivity rates against different VLPs, especially against GII (89–100%). The NV+D- group had higher percent positivity (89% vs. 61%, p=0·03) and median titer (1:100 vs 1:50, p=0·01) of NV-IgA than the NV+D+ group against GI·1 VLPs. A relatively high correlation between different GII·4 variants (0·87) and low correlation between genogroups (0·23–0·37) were observed.

Discussion: Breast milk contained NV-IgA that reacted to various VLPs which may be due to different NV-genotype exposure of mothers. Norovirus-IgA may provide temporary protective coating in the gastrointestinal mucosa and block the interaction of NV and histo blood group antigen which is believed to facilitate viral entry to the host.

Conclusion: Mothers with high positivity rates and titers of breast milk NV-IgA had infants with reduced diarrheal symptoms. Antigenic relatedness to the genetic diversity of human norovirus was suggested.