# Induction of strong and durable cellular and humoral immunity against HIV using DNA-LNPs

> **NIH AI R01** · EMORY UNIVERSITY · 2026 · $909,998

## Abstract

The overall goal of this proposal is to develop a vaccination strategy that induces strong and durable humoral
and cellular immunity against HIV, providing long-term protection even with low neutralizing antibody (Ab)
responses using DNA-LNP technology. Developing an effective HIV-1 vaccine has been an elusive goal for over
four decades. An ideal HIV vaccine should generate a potent and broadly cross-reactive neutralizing antibody
response (bnAb) that remains at high titers for many years. Native-like trimeric HIV envelope (Env) gp140
immunogens, such as SOSIP, NFL, and UFO, have significantly advanced the field by eliciting autologous nAbs;
however, they do not induce an antibody response with neutralization breadth. We and others have shown that
a serum neutralization titer of around 300 or higher is necessary for nearly complete protection in non-human
primates (NHPs). These findings underscore the importance of developing vaccination methods that maintain
persistent nAb levels at or above this threshold. Besides nAbs, CD8 T cells—especially tissue-resident memory
T cells—are crucial for protection against HIV. Our recent studies indicate that adding a T cell-inducing vaccine
to an nAb-inducing vaccine can significantly lower the neutralization titer threshold needed for long-term
protection against intravaginal SHIV challenges, bringing it below detectable levels. Therefore, we hypothesize
that vaccine approaches that induce strong, lasting CD8 T cell responses, along with neutralizing antibodies, will
improve protection against HIV—even when serum neutralizing antibody levels are low. In ongoing studies, we
compared the immunogenicity of mRNA-LNPs with DNA-LNPs expressing SIV Gag in rhesus macaques (RMs).
We observed that DNA-LNPs elicit 25-fold higher levels of Gag-specific CD8 T cell responses compared to
mRNA-LNPs. Moreover, the CD8 T cells induced by the DNA-LNP vaccine were durable, showing only about 2-
fold contraction over four months post-boost. The DN

## Key facts

- **NIH application ID:** 11411705
- **Project number:** 1R01AI200749-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rama Rao  Amara
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $909,998
- **Award type:** 1
- **Project period:** 2026-05-05T00:00:00 → 2031-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11411705

## Citation

> US National Institutes of Health, RePORTER application 11411705, Induction of strong and durable cellular and humoral immunity against HIV using DNA-LNPs (1R01AI200749-01). Retrieved via AI Analytics 2026-07-02 from https://api.ai-analytics.org/grant/nih/11411705. Licensed CC0.

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