# Design and optimization of DL-NLTs and molecular adjuvants to increase potency and promote NAb formation in vivo

> **NIH NIH U19** · WISTAR INSTITUTE · 2024 · $1,327,040

## Abstract

Project 1 Summary
Extensive efforts have been carried out over the years to design a HIV-1 vaccine candidate which
elicits robust immune responses supporting broad neutralization and effector T cell responses.
Recently the Weiner and Kulp laboratories reported the development of novel DNA-launched, in
vivo, self-assembling immunogens, including both DNA launched native like trimers (DL-NLTs)
and DNA-launched nanoparticle immunogens (DLNPs). Both DNA launched NLTs and NPs
assemble and display appropriate epitopes for neutralizing antibodies while occluding epitopes
for non-neutralizing antibodies in vivo. Additionally, they drive robust T cell immunity. These
vaccine candidates are being moved to the clinic under studies HVTN-304 and HVTN-305.
synDNA facilitates rapid immunogen design, co-delivery of molecular adjuvants, supports
expression and assembly of complex structural antigens in vivo, has a safe clinical track record,
and maintains boost-ability. Building on progress from our previous IPCAVD, combining these
designs, we will be working with Dr. Kulp under Project 2 to formulate DLNPs bearing NLTs
displaying Apex and CD4 binding-site B cell lineage targeting Epitopes (DLNP-ACEs).
Furthermore, we have designed and characterized several synDNA-encoded molecular adjuvants
to support enhanced humoral immunity, cell-mediated immunity, and direct antigen-specific
responses to mucosal surfaces. The overarching goal of Project 1 is to combine these novel
immunogens with DNA-delivered genetic adjuvant combinations and/or heterologous adjuvant
regimens, in dual expressing plasmids developed with Project 3 to support vaccine-induced
immunity and represents a great leap forward in the design of HIV-1 vaccines.

## Key facts

- **NIH application ID:** 10751005
- **Project number:** 5U19AI166916-02
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** DAVID B. WEINER
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,327,040
- **Award type:** 5
- **Project period:** 2022-12-08 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751005

## Citation

> US National Institutes of Health, RePORTER application 10751005, Design and optimization of DL-NLTs and molecular adjuvants to increase potency and promote NAb formation in vivo (5U19AI166916-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10751005. Licensed CC0.

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