# Development of an mRNA-Based Therapeutic HIV/AIDS Vaccine

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $823,817

## Abstract

PROJECT SUMMARY
Although the advent of combination antiretroviral therapy (cART) has dramatically improved the prognosis of
people living with human immunodeficiency virus (HIV), cART alone cannot eradicate the infection and,
therefore, daily treatment must be maintained for life to prevent relapse of uncontrolled viral replication and
resumption of disease progression. However, lifelong treatment entails both health risks to treated individuals
and a significant economic burden to society. As such, there is a pressing need to develop novel therapeutic
interventions to cure HIV. Since most examples of stringent, long-term, spontaneous and vaccine-associated
immune control of HIV and simian immunodeficiency virus (SIV) infection are either known, or strongly suspected
to be CD8+ T cell-mediated, therapeutic strategies designed to exploit CD8+ T cell immunity hold great promise
for achieving durable control of virus replication in the absence of cART, often referred to as a “functional cure”.
However, in most people, naturally occurring CD8+ T cell responses induced by HIV infection are often
ineffective at controlling the virus. As such, any HIV cure strategy based on enhancing CD8+ T cell immunity
would need to elicit immune responses that are qualitatively and/or quantitatively different from those that
emerge during primary infection and are subsequently maintained during cART. In addition, in the setting of cure
where the rebound-competent viral reservoir is systemically distributed, having high frequencies of effector-
differentiated and functionally potent anti-viral CD8+ T cell responses pre-positioned in sites of potential viral
rebound (even in immune privileged sites such as B cell follicles) at the time of cART cessation is likely to be
critical for achieving durable post-cART viral control. In this project, we will determine whether a therapeutic
vaccination strategy that utilizes the messenger ribonucleic acid (mRNA)-based vaccine platform RNActive,
can enhance cellular immunity in SIV-infected rhesus macaques (RM) on cART and establish high-level, long-
term control of SIV replication after cART cessation. The choice of this vector is based on preliminary data
demonstrating RNActivevaccines with SIV gene inserts (mRNA/SIV) are highly immunogenic in RM, with the
capacity to elicit potent, systemically distributed, SIV-specific CD8+ T cells with broad epitope recognition. Here
we will assess whether mRNA/SIV vaccination alone or in combination with anti-CD20 B cell depletion (to disrupt
B cell follicles) can facilitate immediate interception of rebounding viral reservoirs to facilitate durable control of
SIV replication after cART cessation. Any finding of vaccine efficacy in this project will provide strong impetus
for clinical assessment of the RNActiveplatform in cART-suppressed HIV+ patients and potentially lead to a
clinically translatable therapeutic approach to achieve HIV infection remission off cART.

## Key facts

- **NIH application ID:** 10364654
- **Project number:** 5R01AI152609-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Afamefuna Okoye
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $823,817
- **Award type:** 5
- **Project period:** 2020-03-05 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364654

## Citation

> US National Institutes of Health, RePORTER application 10364654, Development of an mRNA-Based Therapeutic HIV/AIDS Vaccine (5R01AI152609-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10364654. Licensed CC0.

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