# Comparison of Dendritic Cell-Based Therapeutic Vaccine Strategies for HIV Functional Cure

> **NIH NIH U01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $1,184,950

## Abstract

PROJECT SUMMARY
Dendritic cell (DC)-based therapeutic vaccines have shown the most promise for controlling HIV replication
without antiretroviral therapy (ART). Although two seminal clinical trials demonstrated significant decreases in
plasma viremia without ART that were associated with vaccine-induced HIV-specific immune responses, other
DC-based vaccine studies have shown equivocal or no virologic efficacy. The disconnect between a DC-based
vaccine's theoretical capability, supported by strong in vitro evidence of priming of effector T-cells, and the
variable results of clinical trials, highlight important gaps in understanding the determinants of DC vaccine
efficacy in vivo. We therefore propose a comparative analysis to confirm prior efficacy of DC vaccines and to
test new, innovative DC vaccines with the dual goals of improving virological efficacy and identifying key
determinants of DC vaccine efficacy. Specifically, we will conduct an initial phase I/II, randomized, double-
blind, pilot study to compare safety and anti-HIV efficacy of four different DC-based vaccines and two
corresponding placebos. The trial will evaluate two DC maturation techniques (the prostaglandin E2-matured
DCs, which were partially effective in the two seminal clinical trials, and the alpha-type-1 DCs, which have
shown improved antigen-presenting and T-cell priming function ex vivo), two HIV immunogens (whole,
inactivated, autologous HIV that was partially effective in the two trials, and a pool of HIV peptides covering the
most highly-conserved regions in Gag and Pol combined with epitopes known to be associated with control of
viremia in untreated HIV-infected individuals), and two dosing strategies (3 vs 6 doses). The primary efficacy
outcome will be change in the inducible HIV reservoir from pre-vaccination to 2 weeks after the final vaccine
dose. We will also further evaluate the in vivo anti-HIV efficacy of the DC vaccines by performing an extensive
analysis of vaccine-induced changes in virologic and immunologic parameters with the secondary goal of
identifying immune correlates of vaccine-induced virologic responses. The parameters measured will include
residual plasma viremia, the number and transcriptional activity of HIV-infected cells, CD8+ T-cell inhibition of
autologous virus replication, the magnitude, breadth, and polyfunctionality of immune responses, and
immunoregulatory responses including regulatory T-cells and myeloid-derived suppressor cells. We propose a
second clinical trial to assess reproducibility of initial findings from the first trial and to assess the impact of
further refinements of DC vaccine designs on efficacy. We have developed pre-specified Go/No-Go criteria for
moving forward to a second trial. The decision whether a specific DC vaccine will be evaluated in the second
trial will be based on the primary and secondary virologic and immunologic endpoints of the first trial. This
innovative, sequential, and iterative approach will ...

## Key facts

- **NIH application ID:** 10198701
- **Project number:** 5U01AI131285-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Bernard Jonas C Macatangay
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,184,950
- **Award type:** 5
- **Project period:** 2017-07-14 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198701

## Citation

> US National Institutes of Health, RePORTER application 10198701, Comparison of Dendritic Cell-Based Therapeutic Vaccine Strategies for HIV Functional Cure (5U01AI131285-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10198701. Licensed CC0.

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