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Grant Abstract: Maternal and infant immunization to eliminate breast milk transmission of HIV-1

Grant Number: 5P01AI117915-03
PI Name: Permar
Project Title: Maternal and infant immunization to eliminate breast milk transmission of HIV-1

Abstract: Over 19 million pregnant women are vitamin A deficient. Vitamin A plays an important role in the immune system and deficiency may decrease immune response to vaccines. In HIV infected pregnant women, vitamin A deficiency (VAD) is also associated with increased mortality, premature delivery, and increased mother-to-child transmission of HIV. While vitamin A supplementation of VAD women appears to reduce mortality and prematurity, it is less clear how vitamin A supplementation during pregnancy influences host immune responses, including antibody responses in breast milk, induced in response to vaccination. Since our goal in the funded PO is to develop an HIV vaccine for administration to pregnant women and newborn babies, Vitamin A status of the host is one variable that may greatly impact the quantity and quality of vaccine-induced immune responses.
Studies proposed in this supplement will support our long-term goal of developing effective HIV vaccines for maternal immunization while providing new data related to the benefit of supplementation with vitamin A at the time of maternal vaccination. Studies performed in Aim 1 will determine if maternal vitamin A supplementation of vitamin A deficient rabbits will enhance the induction of vaccine-specific antibodies in the mother and offspring. We hypothesize that supplementation with vitamin A in the form of retinyl palmitate combined with maternal vaccination will enhance vaccine-induced antibody responses and increase placental and breast milk passive transfer of gp120-specific antibodies to kits. The immunization regimen tested will include a priming immunization with modified vaccinia Ankara (MVA) expressing HIV-1 gp120 followed by boosting with HIV-1 gp120 protein. Studies will be performed to evaluate 1) vitamin A supplementation administered at the same time as vaccination, 2) vitamin A supplementation administered one day prior to vaccination or 3) repeated doses of vitamin A supplementation until the vitamin A deficiency is corrected.
Studies performed in Aim 2 will determine if maternal vitamin A supplementation combined with vaccination results in increased protection of offspring from a lethal virus challenge. The use of modified vaccinia Ankara (MVA) expressing HIV-1 gp120 in our prime/boost immunization regimen allows the use of rabbitpox challenge as a surrogate virus challenge. Offspring born to vaccinated rabbits treated with retinyl palmitate or left untreated will be exposed to a lethal dose of rabbitpox to determine if maternal vitamin A supplementation combined with vaccination influences protective immunity in their offspring. We hypothesize that maternal vitamin A supplementation combined with vaccination will provide superior protection of kits against rabbitpox associated morbidity and mortality. This work will contribute to the optimization of maternal vaccine strategies to induce effective responses in blocking mother to child transmission of HIV-1.


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