# Research Project 2:  Antigen design and immunological evaluation

> **NIH NIH U19** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $1,758,323

## Abstract

In Project 2 (P2) we will use cutting-edge antigen engineering to refine vaccine antigen design strategies through
iterative assessments of immunogenicity and protective efficacy to generate optimized vaccine immunogens
against nairo-, hanta-, and paramyxoviruses. Our approach will establish a protective antigen engineering
blueprint for emerging bunyaviruses and paramyxoviruses with pandemic potential. We will interact with the other
PROVIDENT projects and cores for antigen production (CC), animal efficacy testing (CD), mRNA vaccines (P3,
CE), and sharing knowledge and resources (CB, P1, P3, P4). Aim P2.1: Structure-based antigen design. We
will utilize an in-depth understanding of structural biology of viral surface proteins to design and express
recombinant viral antigens from a prototype nairovirus (Crimean-Congo hemorrhagic fever virus, CCHFV),
hantavirus (Andes virus, ANDV), and paramyxovirus (Menangle virus). Following optimization of antigen designs
for prototype viruses, design strategies will be applied to related but genetically distant outgroup viruses
(nairoviruses: Hazara virus; hantaviruses: Sin Nombre virus and Hantaan virus; paramyxoviruses: Sosuga virus
and Nipah virus) to validate that our vaccine design approach is applicable within virus families. Aim P2.2:
Antigenicity and protective efficacy of engineered antigens. We will vaccinate animals with recombinant antigens
designed in P2.1 and produced by CC and evaluate immunogenicity and in vivo efficacy against viral infection.
Following down-selection, lead antigens will be incorporated into mRNA vaccine platforms optimized by P3.
Comparative immunogenicity and in vivo efficacy studies will evaluate recombinant- and mRNA-based vaccine
platforms head-to-head. Based on results obtained using prototype viruses from each family, we will apply
antigen design strategies to outgroup viruses and evaluate immunogenicity and protective efficacy of lead
candidates in existing and/or novel animal models being developed by CD. Aim P2.3: Characterization of
humoral immune responses to engineered antigens. We will evaluate humoral immune responses to engineered
antigens using samples collected from animal studies (P2.2) using high-throughput, well-characterized assays.
We will use authentic and surrogate virus assays to rapidly evaluate neutralization potential and Fc-mediated
activity of vaccine-elicited polyclonal antibodies. VH-VL antibody repertoires encoded by peripheral B cell
subsets will be identified using novel multivalent BCR-seq methodologies. We will also investigate correlates of
protection for lead CCHFV and ANDV vaccine antigens from P2.2 by executing B cell depletion studies with
support from CD. Aim P2.4: Evaluations of T cell responses to engineered antigens. We will perform in-depth
analyses of peripheral, tissue resident, and follicular memory T cell responses in vaccinated animals and will
conduct T cell receptor sequencing to identify the breadth and diversity of T cel...

## Key facts

- **NIH application ID:** 10863599
- **Project number:** 1U19AI181977-01
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Steven Bradfute
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,758,323
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10863599

## Citation

> US National Institutes of Health, RePORTER application 10863599, Research Project 2:  Antigen design and immunological evaluation (1U19AI181977-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10863599. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*