# Vaccine immunogenicity and efficacy in the rhesus macaque/SHIV model

> **NIH NIH U19** · UNIVERSITY OF LOUISIANA AT LAFAYETTE · 2021 · $507,591

## Abstract

Project 2 seeks to test virosomal vaccine immunogenicity and efficacy in the rhesus macaque (RM)/SHIV model.
Mymetics has improved virosomal vaccines built from empty influenza virus-like particles that display an
elongated HIV gp41 peptide on their surface (virosome-P1) or recombinant truncated HIV gp41 (virosome-
rgp41). Earlier, Chinese RMs given two intramuscular (IM) primes followed by two intranasal (IN) boosts were
100% protected from persistent systemic infection and did not seroconvert to SIV Gag after low-dose intravaginal
SHIV challenges. A follow-up study in Indian RMs showed 78% to 87% protection as long as the SHIV dose was
~7x104 times the median HIV inoculum in human male-to-female HIV transmission, but when the SHIV inoculum
was ~105x greater, protection was lost. In these NHP studies, unadjuvanted, liquid formulations of the
combination of virosome-P1 + virosome-rgp41 were used. To improve immunogenicity, Mymetics embedded the
toll-like receptor (TLR)7/8 adjuvant 3M-052 directly into virosome membranes and developed solid, cold-chain
independent vaccine formulations that can be administered needle-free. The powdered virosome forms can be
given as IN spray, sublingual (SL) tablets, or packaged into oral capsules (PO). Our overall hypothesis is that
the cold-chain independent, needle-free adjuvanted solid virosome forms are significantly more immunogenic
than their earlier liquid form in RMs and will induce higher mucosal fluid Ab levels after mucosal priming/mucosal
boosting via different routes. Mymetics has performed pilot tests in small animals with the IN and SL forms;
vaccine delivery via oral capsules needs to be optimized in RMs. The Specific Aims for Project 2 are to:
1. Optimize vaccine delivery to the ileum via enteric-coated capsules; a) monitor passage of capsules
 containing 99mTc or 64Cu by scans; b) attach fluorescent labels to the virosomal vaccines for detection in the
 near-infrared spectrum. Tissues collected at necropsy will be tested by fluorescent microscopy.
2. Test the immunogenicity of different routes of the novel adjuvanted virosomes through a prime/boost
approach. We will test their relative immunogenicity via IN, SL and PO routes; boosts will be given via a
 different mucosal route, a novel approach. Controls will be immunized IM with the soluble virosomal vaccine.
3. Test the efficacy of the cold-chain independent, needle-free, adjuvanted virosomal vaccines against repeated
low-dose intrarectal (IR) clade B SHIV (SHIV-B) challenges. The most immunogenic mucosal prime/mucosal
 boost regimen (see Aim 2) will be used to immunize a group of 12 RMs; control (n=12) will receive empty
 virosomes. All RMs will undergo ~10 weekly low-dose IR challenges with the tier 2, R5 clade B SHIVSF162P3.
4. Test whether RMs that resisted multiple SHIV-B challenges will be protected against cross-clade challenge
with the tier 2 R5 clade C SHIV. Protected RMs will be used to determine correlates of protection.
These innova...

## Key facts

- **NIH application ID:** 10158413
- **Project number:** 5U19AI142636-04
- **Recipient organization:** UNIVERSITY OF LOUISIANA AT LAFAYETTE
- **Principal Investigator:** Ruth Margrit Ruprecht
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $507,591
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158413

## Citation

> US National Institutes of Health, RePORTER application 10158413, Vaccine immunogenicity and efficacy in the rhesus macaque/SHIV model (5U19AI142636-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10158413. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*