# The impact of vitamin A on the gut-mammary gland-secretory IgA axis during enteric viral infections

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2021 · $460,503

## Abstract

Project Summary. Enteric viruses are a major cause of neonatal morbidity/mortality in humans and animals. The
severe gastroenteritis and deaths in neonatal piglets caused by porcine epidemic diarrhea virus (PEDV) have resulted
in multimillion-dollar losses to the swine industry. Similar to the devastating effects of PEDV in swine, rotavirus (RV) is
a leading cause of diarrhea and mortality in children worldwide, as well as in nursing and weaned piglets. Current live
attenuated oral RV vaccines that are efficacious in developed countries, lack efficacy in impoverished countries where
micronutrient deficiencies [vitamin A deficiency (VAD)] are common. Thus, enhancing both maternal immunity and
passive lactogenic immunity via colostrum/milk, are ideal and effective strategies to reduce the impacts of viral
diarrheas in nursing neonates. An understanding of the induction of intestinal immunity during pregnancy and its role
in trafficking of virus specific plasmablasts from the gut to the mammary gland (MG) and secretion of IgA into milk [via
the gut-MG-secretory IgA (sIgA) axis] is lacking. Vitamin A (VA) has pleiotropic effects on the immune system
including induction of mucosal immunity (IgA) and trafficking of B and T cells among mucosal compartments.
However, the role of VA in induction and maintenance of lactogenic immunity against enteric viral infections is largely
undefined. Specifically, pregnant sows and women experience a decline in VA levels during the third trimester. Also
many pregnant women, particularly in developing countries, are affected by VAD, but its impact on maternal and
lactogenic immunity against enteric viruses is unknown. Recently, we observed that oral VA supplementation of
PEDV-infected pregnant swine enhances passive protection of their neonatal suckling piglets. We also showed that
prenatal VAD impairs anamnestic RV-specific IgA antibody secreting cell (ASC) responses in piglets. To expand
knowledge of lactogenic immunity, we will evaluate the impact of VA on: i) induction of virus-specific primary and
secondary (memory) immune responses in pregnant sows; ii) trafficking of virus-specific IgA ASC from intestine to
MG; and iii) lactogenic immunity-induced neonatal protection against PEDV and RV. Our Specific Aims will focus on
elucidating the effect of VA supplementation in VAD pregnant sows, compared with vitamin A sufficient sows on the
following: Aim 1) upregulation of homing molecules and trafficking of immune cells via the gut-MG-sIgA axis and
modulation of gut/MG immune responses in uninfected pregnant sows; Aim 2) enhancing lactogenic immunity after
primary PEDV infection of pregnant sows and piglet passive protection to PEDV challenge (model epidemic virus
infection); and Aim 3) maintenance and reactivation of anamnestic RV-specific IgA memory B cell responses in RV re-
exposed pregnant sows and piglet passive protection to RV challenge (model zoonotic/endemic virus infection).
Our dual purpose/dual benefit stud...

## Key facts

- **NIH application ID:** 10147744
- **Project number:** 5R01HD095881-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Linda J. Saif
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $460,503
- **Award type:** 5
- **Project period:** 2018-08-08 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147744

## Citation

> US National Institutes of Health, RePORTER application 10147744, The impact of vitamin A on the gut-mammary gland-secretory IgA axis during enteric viral infections (5R01HD095881-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10147744. Licensed CC0.

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