@article{e3ca53644ba94f32953dc7f9e2785d12,
title = "Norovirus-specific immunoglobulin A in breast milk for protection against norovirus-associated diarrhea among infants.",
abstract = "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. The cross-reactivity was estimated based on the correlation of ratio between NV-IgA against GII·4 variants and non-GII·4 genotype VLPs. Findings: 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=0·03) 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. Interpretation: Mothers with high positivity rates and titers of NV-IgA in breast milk had NV infected infants with reduced diarrheal symptoms. Antigenic relatedness to the genetic diversity of human norovirus was suggested.",
keywords = "Breast milk, Diarrhea, Immunoglobulin A, Maternal immunity, Norovirus",
author = "Labayo, {Hannah Karen Mina} and Pajuelo, {Monica J.} and Kentaro Tohma and Ford-Siltz, {Lauren A.} and Gilman, {Robert H.} and Lilia Cabrera and Holger Mayta and Sanchez, {Gerardo J.} and Cornejo, {Anniuska Toledo} and Caryn Bern and Clyde Dapat and Tomonori Nochi and Parra, {Gabriel I.} and Hitoshi Oshitani and Mayuko Saito",
note = "Funding Information: HKML, MJP, KT, LAFS, RHG, LC, HM, GJS, ATC, CB, CD, TN, and GIP have no conflict of interest. HO reports grants from AMED and grants from the Ministry of Land, Infrastructure, Transport and Tourism, and Japan Science and Technology Agency, outside the submitted work. MS reports grants from National Institute of Health (NIH) and Japan Society for the Promotion of Science (Fostering Joint International Research B) during the conduct of the study; grants from the Ministry of Land, Infrastructure, Transport and Tourism, Japan Science and Technology Agency, Japan Society for the Promotion of Science, and Japan Agency for Medical Research and Development (AMED), outside the submitted work. Funding Information: This study was funded by the National Institute of Allergy and Infectious Diseases, National Institute of Health under cooperative agreement 1RO1AI108695–01AI and the Japan Society for the Promotion of Science (Fostering Joint International Research B) under grant number 19KK0241. This work was partially supported by the US Food and Drug Administration (FDA) intramural funds. KT is a recipient of a CBER/FDA-sponsored Oak Ridge Institute for Science and Education (ORISE) fellowship. Finally, HKML would like to thank the Ministry of Education, Culture, Sports, Science, and Technology in Japan (MEXT) for her academic scholarship. Funding Information: HKML designed, implemented, and managed this study; performed the laboratory assays and data analysis and develop the main manuscript. MJP designed, managed, coordinated fieldwork, sample collections, and data analysis in Peru. RHG acquired the grant funds; supervised the study. LC supervised the cohort study and sample and data collection in the field. CB contributed to the design of the study, acquisition of grant funds, and editing of the manuscript. HM, GJS and ATC did the laboratory assays and genomic analysis in Peru. KT, LAFS, and GIP provided VLPs, supervised the laboratory assays and interpretation, and edited the manuscript. CD oversaw the laboratory assays and analysis in Japan and edited the manuscript. TN and HO supervised the mucosal and virological aspects of this study respectively. MS designed, implemented, and managed the study and acquired the grant funds. All authors reviewed the draft and approved the final manuscript submitted for publication. This study was funded by the National Institute of Allergy and Infectious Diseases, National Institute of Health under cooperative agreement 1RO1AI108695?01AI and the Japan Society for the Promotion of Science (Fostering Joint International Research B) under grant number 19KK0241. This work was partially supported by the US Food and Drug Administration (FDA) intramural funds. KT is a recipient of a CBER/FDA-sponsored Oak Ridge Institute for Science and Education (ORISE) fellowship. Finally, HKML would like to thank the Ministry of Education, Culture, Sports, Science, and Technology in Japan (MEXT) for her academic scholarship. The data that support the findings of this study are available from the corresponding author, M.S. upon reasonable request. We are grateful to the norovirus working group of Universidad Peruana Cayetano Heredia who supported this study. We also want to thank the families of Villa El Salvador community who participated in this study, the field workers for their hard work and dedication, and to all the leaders at the study site who generously provided their support during the conduct of the study. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = oct,
doi = "10.1016/j.eclinm.2020.100561",
language = "English",
volume = "27",
journal = "EClinicalMedicine",
issn = "2589-5370",
publisher = "Lancet Publishing Group",
}
