# Reversal of HIV Cognitive Disease in Mice Employing Broadly Specific T Cell Vaccines

> **NIH NIH R03** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $84,750

## Abstract

PROJECT SUMMARY
 This R03 application requests funds for research in an area of high relevance to the mission of
the NINDS; specifically, to use an existing mouse model of HIV-associated neurocognitive impairment
(HIV-NCI) for preclinical testing of therapeutic vaccination to reverse the disease employing T cell
vaccines against conserved determinants present on HIV worldwide. People living with HIV due to
successful combination antiretroviral therapy CART have low HIV burdens, functioning immune
systems, and are relatively healthy, but about half of them develop chronic HIV-NCI that is not currently
treatable. The disease is believed to be driven by myeloid cell reservoirs of HIV that defy the CART-
restored anti-HIV immune surveillance. This small grant application proposes to use our well-
established model of HIV-NCI in conventional mice infected by chimeric HIV, EcoHIV, to test
therapeutic vaccination against the disease using state of the art broadly specific mosaic Gag-Pol T cell
vaccines created by our collaborator Dr. Tomas Hanke. As recently reported, HIV-NCI in EcoHIV
infected mice can be reversed by intranasal insulin treatment, suggesting that neurons relevant to
cognition remain viable despite HIV insult, consistent with spontaneous cognitive improvement seen in
some patients with NCI. As shown in Preliminary Results, innate immune stimulation also reverses HIV
NCI in infected mice, as well as reduces virus burdens, suggesting that infected cells can directly be
controlled through immunological routes. Dr Hanke's previous T cell vaccines protect mice from
EcoHIV infection, as shown in our collaboration. Importantly, the vaccines to be employed, presented
as Gag-Pol mosaic constructs, carry globally conserved determinants that are also associated with low
virus burden in human beings and have entered clinical evaluation. The overall goal of this proposal is
to test the novel mosaic vaccines for their ability to affect virus burden and behavioral change in
EcoHIV-infected mice with NCI. The Aim is a) to optimize responses to DNA-, replication-deficient
poxvirus MVA-, and replication-deficient adenovirus-vectored vaccines for reduction of virus burden and
recovery of learning and memory in HIV-NCI mice; and b) to begin to identify antigenic determinants
recognized by T cells associated with protective responses. Methods include immunization routes,
assessment of virus burden in various tissues, memory and learning tests, and assay of peptide
responses of CD4 and CD8 T cells. This pilot study will form the basis of a comprehensive study to
employ therapeutic vaccination to boost adaptive immune responses to globally shared HIV
determinants to reverse or prevent the development of HIV cognitive disease in infected people.

## Key facts

- **NIH application ID:** 10019599
- **Project number:** 5R03NS117157-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** MARY Jane POTASH
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $84,750
- **Award type:** 5
- **Project period:** 2019-09-30 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019599

## Citation

> US National Institutes of Health, RePORTER application 10019599, Reversal of HIV Cognitive Disease in Mice Employing Broadly Specific T Cell Vaccines (5R03NS117157-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10019599. Licensed CC0.

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