# Virus-Like Nanoparticles for Non-Capsid Antigen Delivery with Virus Structure/Functional Mimicry to Activate B Cell Immunity

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $513,210

## Abstract

Various nanoparticles (NPs) have been used for delivery of small antigens, which have limited viral mimic
features and are more efficacious than soluble antigens in stimulating B-cell immunity. However, these traditional
NPs lack characteristics of virus “spiky capsid protein peplomer”, e.g. spiky antigen clusters on the peplomers,
optimal distance between antigen clusters, and highly localized antigen density on the spike. It is unknown how
the lack of virus-like features of traditional NPs affect B cell immunity and durable antibody responses.
Although virus-like features of B cell vaccine for durable B cell immunity are clinically validated using virus-like
particles (VLPs) of viral capsid proteins, VLPs are not suitable for delivery of non-capsid small antigens (such as
bacterial toxins, small molecules, and oncogenic peptides) since these non-capsid small antigens are not able
to self-assemble to VLPs. There is a need to develop virus-like nanoparticles for small antigens to activate B cell
immunity against deadly bacterial toxins (Anthrax, Botulinum), small molecules, and oncogenic peptides.
Three components of B cell immunity are critical for durable antibody response: (A) Efficient antigen
delivery/retention and unique antigen distribution patterns for B cell acquisition in the draining lymph nodes
(dLNs), (B) Activation of antigen-specific B cells through multivalent binding/crosslink with B cell receptor (BCR),
(C) Activation of follicular T Helper cells (Tfh) that support Germinal Center (GC) B cells and their differentiation
to long-lived plasma cells (LLPCs). However, it is unknown how the lack of virus-like features of NPs antigen
delivery systems affect these three critical components of B cell immunity for durable antibody response.
In this proposal, we will generate inorganic virus like nanoparticles (IVLNs) with three features of spiky peplomers
of virus' using four types of small antigens (peptides of anthrax and botulinum toxins, small molecule 4-hydroxy-
3-nitrophenyl acetyl-hapten, HER2 peptides) to test our hypothesis. We hypothesize that: (A) Virus-like features
of IVLNs enhance efficient delivery/retention with unique antigen distribution patterns for B cell acquisition in the
lymph node, (B) Virus-like features of IVLNs enhance B cell activation via multivalent bind/crosslink with B cell
receptor, promote follicular T (Tfh) cell-dependent B-cell activation, enhance formation of long-lived plasma cells
(LLPCs) in the Germinal Center (GC), and generate antibodies with high specificity/affinity, (C) Virus-like features
of IVLNs induce durable antibody response against bacterial toxins (anthrax and botulinum) and oncogenic
antigens.
Aim 1 Determine virus-like features of IVLNs to improve antigen delivery/retention with unique antigen
distribution patterns for B cell acquisition in the lymph nodes vs. traditional NPs
Aim 2 Identify the stages of B cell responses by the virus-like features of IVLNs vs. traditional NPs
Aim 3 In...

## Key facts

- **NIH application ID:** 10044823
- **Project number:** 1R01AI154072-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Irina Leonidovna Grigorova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $513,210
- **Award type:** 1
- **Project period:** 2020-07-07 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10044823

## Citation

> US National Institutes of Health, RePORTER application 10044823, Virus-Like Nanoparticles for Non-Capsid Antigen Delivery with Virus Structure/Functional Mimicry to Activate B Cell Immunity (1R01AI154072-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10044823. Licensed CC0.

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