# Therapeutic vaccination and PD-1 blockade in treated HIV disease

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $1,336,452

## Abstract

ABSTRACT
The central premise of our program is that durable control of HIV in the absence of antiretroviral therapy
(“remission”) will require the generation of de novo potent and sustained HIV-specific CD8+ cell responses that
target evolutionarily conserved epitopes. Our program is inspired by the recent success of VGX-3100 (Inovio),
a DNA therapeutic vaccine for HPV that leads to histopathologic regression of pre-malignant lesions in people
and is associated with a potent, sustained boost to HPV-specific CD8+ T cell populations. A closely related
multi-clade gag/pol/env DNA vaccine (PENNVAX, Inovio) has been studied for HIV prevention and is known to
be both safe and highly immunogenic. The therapeutic potential of this novel approach is unknown and will be
the focus of our work in the first two years. We are fully aware, however, that administration of a DNA vaccine
alone (PENNVAX-GP) will unlikely be sufficient to achieve a disease remission. The presence of pre-existing
escape mutations and immune dysregulation known to persist during treated HIV disease will hamper vaccine
effectiveness, and adjuvant approaches will be likely be needed. In the first two years, we will determine if IL-
12 can enhance immunogenicity of this vaccine. This work is based on extensive experience in non-human
primates and in HIV-uninfected adults showing IL-12 enhances immunogenicity of DNA vaccines. In Years 3 to
5, we will determine if PD-1 blockade with pembrolizumab (Merck) enhances vaccine effectiveness. This study
will likely test for the first time if PD-1 blockade during active vaccination improves the breadth of the immune
response and increases the numbers of effector cells. Our study will leverage the considerable strengths of our
established multi-disciplinary research team to pursue highly innovative approaches to measuring vaccine
immunogenicity and the viral reservoir. Should we be successful, we will have at the end of this program a
viable vaccine strategy that has a manageable safety profile and is known to be highly immunogenic.

## Key facts

- **NIH application ID:** 10137176
- **Project number:** 5U01AI131296-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** STEVEN Grant DEEKS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,336,452
- **Award type:** 5
- **Project period:** 2017-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137176

## Citation

> US National Institutes of Health, RePORTER application 10137176, Therapeutic vaccination and PD-1 blockade in treated HIV disease (5U01AI131296-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10137176. Licensed CC0.

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