# Prophylactic oral vaccination for SIV and SHIV infections and AIDS prevention

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $460,793

## Abstract

SUMMARY
This proposal is designed to extend our previous studies where we achieved significant systemic and mucosal
cellular responses after oral cavity and intestinal immunizations with a SIV DNA-rMVA approach. These
immunizations had two important impacts on SIV exposure and infection: 1. the intestinal immunization provided
significant protection from infection but no protection from disease progression; 2. the oral cavity immunization
provided significant protection from disease with no AIDS development observed during the post-challenge follow up
and with more than 50% of the animals controlling virus replication to undetectable blood levels after experiencing a
peak of viremia, and apparently clearing the infection, as no rebound was observed after CD8+ T-cell depletion.
Here we propose to investigate in Cynomolgus macaques anti-SIV and SHIV oral immunization approaches aimed
at stimulating cellular immune responses, previously achieved via oral immunization, and persistent anti-Env IgG
and IgA titers, previously sporadic or missing, systemically and at mucosal sites where HIV exposure occurs in
humans. The goal sof the proposal are the following: I. To evaluate how oral immunization regimens composed of 1.
pSIVvaxE543 DNA, boosted with gp140(smE543) Env and rMVA, 2. pSIVvaxE543 DNA + SIVgag239 and
SIVenvsmE543 recombinant OPVs (collectively called SIV-OPV), and 3. SIV-OPV alone compare in their stimulation of
cell mediated and humoral immunity systemically and at mucosal sites where HIV transmission occurs in humans,
and whether they provide protection from heterologous SIVmac251 infection and disease in Cynomolgus macaques
(CM). II. To evaluate stimulation of systemic and mucosal cell-mediated immunity and humoral immunity by three
regimes that include SHIVBG505 DNA + SIVgag239-OPV and HIV Env-OPV, where Env in this last component is linear
HIVBG505 gp140 in Group 1, a SOSIP-gp140 BG505 in Group 2, and a V1-V2 BG505 scaffold in Group 3, and whether
these responses provide protection from heterologous SHIVAD8 infection and disease in CM; III. To evaluate the
extent of anti-HIV Env antibody affinity maturation observed with repeated SHIV-OPV immunization. During these
experiments we will evaluate mechanistic characteristics of the anti-SIV or SHIV immune response and correlates of
protection from infection and disease, with focus on the analysis of intestinal mucosa responses and viral loads, viral
reservoirs, and possibly eradication post infection.

## Key facts

- **NIH application ID:** 9962368
- **Project number:** 5R01DE026325-05
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** ANNA ALDOVINI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $460,793
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962368

## Citation

> US National Institutes of Health, RePORTER application 9962368, Prophylactic oral vaccination for SIV and SHIV infections and AIDS prevention (5R01DE026325-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9962368. Licensed CC0.

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