# INFLUENZA-SPECIFIC IMMUNITY AND RESPONSES TO INACTIVATED INFLUENZA VACCINE IN INFANTS: EFFECT OF MATERNAL VACCINATION DURING PREGNANCY

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $466,498

## Abstract

Immunization of pregnant women is increasingly used to protect mothers and/or infants against vaccine-
preventable diseases. However, there is little knowledge on the effects of maternal vaccination on infant
immune responses. There is growing evidence that infants can develop in utero responses to maternal
vaccines. We hypothesized that in utero exposure to maternal influenza vaccine (IIV) antigens may generate
infant adaptive responses against influenza in utero that may protect the infant against the disease after
maternal antibodies decrease in infant circulation below the threshold of protection. Conversely, in utero
immunization also may generate regulatory T cells (Treg) that downregulate the infant responses to childhood
vaccines. To address these hypotheses, we formulated the following specific aims:
Aim 1. To determine the rate of IIV in utero immunization and the persistence of Flu-specific antibody
and cellular immune responses after in utero immunization.
IIV-exposed immunized infants will be identified by presence of Flu-specific IgA, T cells, or B cells in cord blood
that exceed the 99th percentile of the corresponding markers in IIV-unexposed infants. Persistence will be
defined by the presence of Flu-specific IgA antibodies, memory B cells and T cells at 6 to 18 months of age,
before the administration of the 1st dose of IIV to the infant.
Aim 2. To determine the effect of IIV in utero immunization on subsequent immune responses to
pediatric IIV administered at 6 to 18 months of life.
We will measure Flu-specific humoral and cellular immune responses to the initial administration of pediatric
IIV in IIV-exposed immunized infants primarily by comparison with IIV-unexposed infants. Responses
measured in this will consist of Flu-specific antibodies, effector and memory B cells and T cells and their
transcription profiles. We will correlate the proportions of Flu-specific Treg before pediatric IIV administration
with the magnitude of the adaptive immune responses developed after completion of the 2 doses of IIV in the
primary pediatric immunization schedule.
Aim 3. To compare the epigenetic profile of Flu-specific T cells generated by in utero immunization or
pediatric IIV administration at 6 to 18 months of life.
T cells that proliferate after ex vivo Flu stimulation of CBMC of IIV-exposed immunized or infant PBMC from de
novo immunized infants will be purified and their epigenetic profile will be compared using ATAC-Seq.
The results of this study will determine the quality, durability and the epigenetic characteristics of the fetal
immune responses to foreign antigens introduced by maternal vaccination. It will define the effect of in utero
immunization on neonatal immunity and inform the practice of vaccination during pregnancy.

## Key facts

- **NIH application ID:** 10197834
- **Project number:** 5R01AI154624-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** ADRIANA WEINBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,498
- **Award type:** 5
- **Project period:** 2020-06-18 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197834

## Citation

> US National Institutes of Health, RePORTER application 10197834, INFLUENZA-SPECIFIC IMMUNITY AND RESPONSES TO INACTIVATED INFLUENZA VACCINE IN INFANTS: EFFECT OF MATERNAL VACCINATION DURING PREGNANCY (5R01AI154624-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10197834. Licensed CC0.

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