# Biomaterials and Nanovaccines

> **NIH NIH P01** · DANA-FARBER CANCER INST · 2020 · $294,448

## Abstract

Project Summary/Abstract 
The development of a vaccine capable of eliciting protective broadly neutralizing antibodies against HIV will 
require the development of improved strategies to control the antigenicity of envelope target antigens and 
adjuvants that can drive high levels of affinity maturation by eliciting sufficient/appropriate T-cell help, 
promoting germinal center development, and drive differentiation of long-lived plasma cells and memory B- 
cells to obtain a durable response. This P01 program focuses particularly on the membrane-proximal external 
region (MPER) of gp41 as a validated target for several broadly neutralizing antibodies, including the recently 
discovered 10E8 antibody that exhibits high potency without evidence of autoreactivity. In collaboration with 
the Reinherz lab (Project 1), we have recently developed a liposomal vaccine platform for delivery of 
hydrophobic, membrane-associated MPER fragments that allows durable, substantial titers against this poorly 
immunogenic peptide to be raised in normal mice. Building on this promising preliminary data and our very 
recent discoveries regarding the role of antigen oligomerization state on liposome surfaces in regulating B-cell 
triggering, we propose here a set of complementary strategies aiming to control the antigenicity and 
immunogenicity of MPER sequences, further enhance Tfh cell development and antibody affinity maturation, 
and promote humoral response durability. We will work in close collaboration with Project 1, providing 
liposomal vaccines and novel adjuvants on demand for their structure-focused studies, while pursuing a 
deeper understanding of how antigen presentation, adjuvant signaling, and T helper cell differentiation impact 
induction of high-affinity antibody responses against the MPER sequence of HIV. Our specific aims are (1) To 
determine the role of MPER oligomerization state on recognition by MPER-specific B-cells and humoral 
immunity, (2) To test strategies for controlling the angle of approach of antibodies to MPER sequences 
displayed on liposomal vectors, (3) To develop novel lymph node targeted adjuvants triggering the STING 
pathway for potent interferon-driven humoral responses, and (4) To test novel adjuvants directly modulating 
signaling pathways in helper T-cells to promote Tfh differentiation and germinal center induction. When 
combined with the structural advances pursued in Project 1, we aim to elicit broadly neutralizing antibodies by 
presenting MPER sequences in a correct configuration together with appropriate adjuvant signals that will 
promote the priming and affinity maturation of MPER-specific B-cells.

## Key facts

- **NIH application ID:** 9982758
- **Project number:** 5P01AI126901-05
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Darrell J Irvine
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $294,448
- **Award type:** 5
- **Project period:** 2016-08-05 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982758

## Citation

> US National Institutes of Health, RePORTER application 9982758, Biomaterials and Nanovaccines (5P01AI126901-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9982758. Licensed CC0.

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