# Characterizing antibody responses to HIV-1 vaccination in next-generation immune humanized mice

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $707,737

## Abstract

PROJECT SUMMARY
 With no universal cure, development of an effective vaccine to prevent HIV-1 infection remains a primary
goal. A major hurdle for the development of successful vaccination strategies has been the lack of affordable,
accessible, tractable, and relevant preclinical model systems. Investigations on HIV infection, pathogenesis, and
prevention using small animal models have been limiting due to the species-specific tropism of HIV. The advent
of immunodeficient mice harboring a human immune system (HIS) in many ways has broadened accessibility
and interest in HIV-related translational studies including viral replication, T cell depletion, methods of
transmission, and evaluation of antiretroviral therapies. Nevertheless, efforts to develop vaccination strategies
against HIV in current HIS mice have been thwarted due to poor adaptive immune responses and antigen-
specific antibody development following immunization. Thus, there is a great need for advances in HIS mice that
promote vaccine-mediated antibody development to specific epitopes that would easily translate to humans. We
hypothesize that enhanced human T cell function and priming via human antigen presenting cells in HIS mice
will facilitate efficient T/B cell interactions and enable evaluation of vaccination strategies against HIV-1. To this
end, we have developed a novel HIS mouse strain expressing human leukocyte antigens (HLA)-DQ and HLA-A
in the absence of murine major histocompatibility complex (MHC) I/II (to ensure human T cell selection on a
more appropriate molecules in the mouse thymus) in combination with human CSF1 knocked into the murine
Csf1 locus. Based on published data from our group and others, this novel strain, we anticipate, will support
improved T cell development/function as well as the development of human myeloid cells with increased capacity
to prime human T cells following immunization and facilitate HIV-1-specific antibody production. We will leverage
this new translational HIS platform to: i) Determine the scope of the human adaptive immune response to
infection with HIV-1 R5 virus, ii) Determine the neutralization ability of, define the Env epitopes targeted by, and
delineate the sequence features for the human adaptive immune response to HIV-1 immunization, and iii)
assess a novel vaccination strategy using optimized multivalent immunogens for broad neutralizing antibodies
(bNAb) elicitation. Together, these results will provide critical insights into the utility of this advanced HIS model
system to assess HIV-1 vaccination strategies capable of generating bNAbs to accelerate prioritization to
validate in human clinical trials.

## Key facts

- **NIH application ID:** 10813126
- **Project number:** 5R01AI176521-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jeremy Allen Goettel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $707,737
- **Award type:** 5
- **Project period:** 2023-03-21 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813126

## Citation

> US National Institutes of Health, RePORTER application 10813126, Characterizing antibody responses to HIV-1 vaccination in next-generation immune humanized mice (5R01AI176521-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10813126. Licensed CC0.

---

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