# Impact of HLA-II Adaptation on CD4 T-cell and Tfh responses in HIV-1 Vaccination

> **NIH NIH F30** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $39,302

## Abstract

PROJECT SUMMARY
The purpose of this NIH F30 application is to obtain support for the PI, Jacob Files, for his mentored research
and career development for the next three years. These activities are part of his training requirements that are
necessary for him to obtain his MD/PhD degree, and they will strengthen his potential to become a successful
physician scientist. The major goal of this project is to develop his skills in order to study CD4+ T-cell responses
(CD4 responses) in HIV-1 vaccine recipients using both immunological laboratory assays and computational
techniques. The primary objective of the research proposal is to investigate the impact of HLA-II associated viral
adaptation on CD4 responses in the setting of HIV-1 vaccination. CD4 responses have been found to play an
important role in generating HIV-specific antibodies; therefore, an optimal CD4 response is likely to be an
important component of future preventative HIV-1 vaccines. Our preliminary studies show that current HIV-1
vaccine studies encode a high percentage of HLA-II associated adapted epitopes and that these adapted
epitopes elicit weaker responses in HIV-1 vaccine recipients compared to HLA-II associated non-adapted
epitopes. Therefore, it is possible that a fully HLA-II non-adapted HIV-1 vaccine could lead to a more optimal
CD4 response. This project will investigate the functionality and heterogeneity of the non-adapted and adapted
epitope-specific CD4 responses, with a focus on identifying epitope-specific Tfh cells in HIV-1 vaccine recipients
(Aim 1). Then, the project will determine the contribution of these CD4 responses to the frequency of HIV-specific
antibodies and to B-cell maturation (Aim 2). By characterizing the functionality of the CD4 responses to these
HLA-II associated epitopes and determining their impact on antibody production, our long-term objective is to
inform future HIV-1 vaccine studies of strategies that can improve HIV-specific antibody production, leading to
durable protection from HIV-1 infection.
The proposed training plan for the PI is sponsored by his PhD mentor, Dr. Paul Goepfert. Included in the training
plan are experiences that will help him develop in three major areas: 1) rigorous immunological research in HIV-
1, which includes developing familiarity with the existing literature, critically evaluating published studies, and
training in principles of scientific integrity and responsible conduct of research; 2) competence in bioinformatic
techniques and biostatistical analysis; and 3) career and professional development, including grant writing,
journal article review, clear communication through presentation and manuscript preparation, and translation of
research findings to clinical applications. After completion, this training plan will provide the PI with the foundation
necessary for a successful career as a physician scientist. His ultimate career goal is to one day lead a
translational research team that performs laboratory-ba...

## Key facts

- **NIH application ID:** 10254574
- **Project number:** 1F30AI155295-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Jacob Files
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $39,302
- **Award type:** 1
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254574

## Citation

> US National Institutes of Health, RePORTER application 10254574, Impact of HLA-II Adaptation on CD4 T-cell and Tfh responses in HIV-1 Vaccination (1F30AI155295-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10254574. Licensed CC0.

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