# Optimizing Adjuvants and Needle Free Delivery Methods for Oral HIV Vaccination

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $788,873

## Abstract

The majority of HIV infections occur via mucosal routes (genital, oral or rectal) world-wide. The overall goal of
this proposal is to develop a vaccination approach that induces strong HIV-specific humoral and cellular
immunity in genital, intestinal and oral mucosae. We hypothesize that vaccines, which elicit strong anti-HIV
immunity at these mucosal sites, will prevent infection and rapidly clear infected cells very early at the site of
infection and enhance protection. Oral cavity is rich in lymphoid tissue containing antigen presenting cells, T
cells and B cells, and provides an excellent opportunity for mucosal delivery of vaccines. However, this route of
immunization has been under utilized to deliver vaccines in part due to the presence of proteases in saliva that
can degrade vaccines. This is particularly true for protein-based vaccines. Here, we aim to target the oral
mucosa for immunization using a needle free device (Syrijet) as an oral vaccine delivery system to induce
strong immune responses at oral and intestinal mucosal sites. The syrijet can deliver vaccines into the oral
mucosa thus will 1) enhance the delivery of vaccine to local lymphoid tissue that will facilitate uptake by DC
and 2) will maintain integrity of the vaccine by preventing degradation by oral proteases. To test our
hypothesis, we will use a heterologous prime/boost regimen consisting of CD40L-adjuvanted DNA, MVA and
protein vaccines expressing SHIV immunogens. In our preclinical macaque studies we showed that CD40L-
adjuvanted DNA/MVA SIV vaccines delivered via IM route provide enhanced protection against intrarectal
neutralization resistant SIV challenges. The addition of systemic protein boost adjuvanted with nanoparticle
encapsulated TLR7/8 agonist to the DNA/MVA vaccine robustly boosted HIV envelope-specific IgG in serum
and also increased antibody in vaginal and rectal secretions. In this proposal, in Aim 1, we will first optimize the
method and location of oral vaccine delivery and compare different adjuvants for protein immunogen. We will
compare sublingual and buccal immunizations delivered with and without syrijet for induction of strong SHIV-
specific humoral and cellular immunity in the oral and gut mucosal tissue. We will also test other mucosal
adjuvants flagellin and dmLT for protein immunizations. In Aim 2, using the best delivery method and adjuvant
combination that we identify in Aim 1, we will conduct an intrarectal challenge study with clade C SHIV. This
study will also focus on understanding the immune correlates for protection. By completion of these Aims we
hope to have identified an efficient mucosal vaccination regimen for enhancing protection against HIV.

## Key facts

- **NIH application ID:** 9900575
- **Project number:** 5R01DE026333-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rama Rao Amara
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $788,873
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900575

## Citation

> US National Institutes of Health, RePORTER application 9900575, Optimizing Adjuvants and Needle Free Delivery Methods for Oral HIV Vaccination (5R01DE026333-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9900575. Licensed CC0.

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