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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. Funding National Institute of Allergy and Infectious Diseases, National Institute of Health: 1R01AI108695–01A1 and the Japan Society for the Promotion of Science (Fostering Joint International Research B):19KK0241

SUBMITTER: Labayo H

PROVIDER: S-EPMC7536734 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Project description:UnlabelledNoroviruses (NoVs) are the leading cause of nonbacterial acute gastroenteritis worldwide in people of all ages. The P particle is a novel vaccine candidate derived from the protruding (P) domain of the NoV VP1 capsid protein. This study utilized the neonatal gnotobiotic pig model to evaluate the protective efficacies of primary infection, P particles, and virus-like particles (VLPs) against NoV infection and disease and the T cell responses to these treatments. Pigs either were vaccinated intranasally with GII.4/1997 NoV (VA387)-derived P particles or VLPs or were inoculated orally with a GII.4/2006b NoV variant. At postinoculation day (PID) 28, pigs either were euthanized or were challenged with the GII.4/2006b variant and monitored for diarrhea and virus shedding for 7 days. The T cell responses in intestinal and systemic lymphoid tissues were examined. Primary NoV infection provided 83% homologous protection against diarrhea and 49% homologous protection against virus shedding, while the P particle and VLP vaccines provided cross-variant protection (47% and 60%, respectively) against diarrhea. The protection rates against diarrhea are significantly inversely correlated with T cell expansion in the duodenum and are positively correlated with T cell expansion in the ileum and spleen. The P particle vaccine primed for stronger immune responses than VLPs, including significantly higher numbers of activated CD4+ T cells in all tissues, gamma interferon-producing (IFN-γ+) CD8+ T cells in the duodenum, regulatory T cells (Tregs) in the blood, and transforming growth factor β (TGF-β)-producing CD4+ CD25- FoxP3+ Tregs in the spleen postchallenge, indicating that P particles are more immunogenic than VLPs at the same dose. In conclusion, the P particle vaccine is a promising vaccine candidate worthy of further development.ImportanceThe norovirus (NoV) P particle is a vaccine candidate derived from the protruding (P) domain of the NoV VP1 capsid protein. P particles can be easily produced in Escherichia coli at high yields and thus may be more economically viable than the virus-like particle (VLP) vaccine. This study demonstrated, for the first time, the cross-variant protection (46.7%) of the intranasal P particle vaccine against human NoV diarrhea and revealed in detail the intestinal and systemic T cell responses by using the gnotobiotic pig model. The cross-variant protective efficacy of the P particle vaccine was comparable to that of the VLP vaccine in pigs (60%) and to the homologous protective efficacy of the VLP vaccine in humans (47%). NoV is now the leading cause of pediatric dehydrating diarrhea, responsible for approximately 1 million hospital visits for U.S. children and 218,000 deaths in developing countries. The P particle vaccine holds promise for reducing the disease burden and mortality.

Project description:ObjectivesThe fatty acid (FA) composition of breast milk is a relevant aspect related to the development of the lactating infant. The present study aimed at exploring correlations between dietary intake of macro- and micronutrients with the FA profile in breast milk, and the possible implication for infants' growth.Study designBreast milk samples from a cohort of lactating women were collected 7-15 days postpartum. The FA profiles in triacylglycerol (TAG) and phospholipid (PL)-rich fractions were analyzed by gas chromatography. Diet was registered during the third trimester of pregnancy by means of a food frequency questionnaire (FFQ). In addition, anthropometric measurements of infants were collected from gestation and up to 12 months postpartum.ResultsThe FA profile in breast milk was characterized by a median of 37.4, 41.3 and 16.8% of saturated, monounsaturated, and polyunsaturated FAs, respectively. From the dietary components, zinc, iron, and B group vitamins were correlated positively with the proportion of total n-3 FAs in TAG and C20:5 n-3 in PL. Lycopene, vitamin E, zinc, and vitamin B2 showed a similar correlation with total polyunsaturated fatty acid (PUFA), total n-6 FAs, C20:4 n-6, and C18:2 n-6 in TAG. Regarding food groups, nuts showed the strongest association with several PUFA both in TAG and PL, while the vegetable group was also positively associated with C18:3 n-3. Furthermore, the concentration of linolenic acid (C18:3 n-3) and palmitic acid (C16:0) were positively associated with increased length for age (LFA) and weight for age (WFA) at 12 months compared with birth [ΔLFA -0.16 (-0.85, 0.37); ΔWFA -0.26 (-0.77, 0.21)].ConclusionsMothers' intake of nuts, dietary sources of zinc, iron, and B group vitamins were identified as potential predictors of a high-unsaturated FA profile in breast milk. In addition, linolenic and palmitic acids in breast milk were positively associated with infants' growth in the first year of life.

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

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