# Novel nanoparticulate adjuvants to enhance HIV-1 Env specific mucosal antibody responses

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $895,998

## Abstract

Abstract
One of the key obstacles to developing an effective HIV-1 vaccine is identifying adjuvants and immunogens that
induce persistent HIV-1 envelope (Env) antigen specific antibody responses of high magnitude. Alum has been
the choice of adjuvant for use in humans for almost a century now and also used in most HIV-1 vaccine clinical
trials. However, Alum fails to induce persistent HIV-1 Env specific antibody responses of the appropriate quality
(neutralizing activity or effector functions). Nanoparticulate adjuvants are known to enhance immune responses
by rapidly draining and targeting key immune cells in lymph nodes. Our recently completed studies evaluating a
novel TLR-7/8 ligand (3M-052) from 3M Pharmaceuticals by itself or in combination with a TLR-4 agonist GLA
formulated in biodegradable synthetic polymer nanoparticles in rhesus macaques has for the first time
successfully induced HIV-1 Env specific long-lived plasma cells (LLPCs) in the bone marrow. Robust and
persistent antibody responses with binding, neutralizing and ADCC activity were also observed at high
magnitude in addition to high frequencies of germinal center B cells and follicular T helper cells in draining lymph
nodes. However, our polymer nanoparticles have faced challenges with manufacturability for use in humans.
Hence, building on our proof of concept studies, in collaboration with the Infectious Disease Research Institute
(IDRI) and 3M Pharmaceuticals, we now propose to a) evaluate a NanoAlum, novel clinically relevant Alum
based nanoparticulate adjuvant with HIV-1 Env immunogens in combination with the 3M-052 molecule, b)
establish new methodology that uses novel serum proteomics and BCR sequencing to rigorously investigate
vaccine induced responses by defining key subsets of LLPCs in RMs and finally c) evaluate vaccine based
protective efficacy upon virus challenge when combining sub-cutaneous vaccinations with such new adjuvants
with intranasal vaccinations (IN) to improve mucosal immunity at genital mucosa.

## Key facts

- **NIH application ID:** 9969327
- **Project number:** 5R01AI145640-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Sudhir Pai Kasturi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $895,998
- **Award type:** 5
- **Project period:** 2019-07-03 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969327

## Citation

> US National Institutes of Health, RePORTER application 9969327, Novel nanoparticulate adjuvants to enhance HIV-1 Env specific mucosal antibody responses (5R01AI145640-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9969327. Licensed CC0.

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