# A systems immunology approach for predicting poor responses to Hepatitis B vaccination

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $791,641

## Abstract

Project Summary
Vaccines are powerful tools for combating infectious diseases yet vaccination may fail to induce robust
antibody responses, even after multiple doses. Yet 2-10% of all vaccinations in healthy people fail to result in
protective immunity, and, in the specific example of hepatitis B virus (HBV) vaccine, chronic inflammatory
states such as obesity are associated with 10-30% of individuals having poor antibody responses, leaving
them unprotected. Moreover, the prevalence of chronic inflammatory states such as obesity is steadily
increasing worldwide, at a time where we more than ever depend on vaccines to prevent infectious diseases
such as COVID-19. Better understanding of mechanisms of poor humoral responses to vaccines are urgently
needed. Vaccine responses involve induction of affinity-matured antibodies by B cells, which requires help
from T follicular helper (Tfh) CD4 cells in germinal centers. We previously identified circulating Tfh, termed
cTfh, which provided help to B cells in vitro and had transcriptional and phenotypic similarities to lymphoid Tfh,
and responded to influenza vaccination in an antigen-specific way, giving us a “window” into lymphoid state
and activity. However, understanding of how cTfh and B cell responses to HBV vaccine are established and
change over time are limited, particularly in humans. Here, we propose to study the HBV vaccine response to
understand factors associated with the strength of the protective antibody response, using a systems
immunology approach in a prospective clinical study of HBV vaccination in the setting of chronic inflammation
induced by obesity. In Aim 1, we will evaluate the effect of repeated antigen exposure by studying the Tfh-B
cell axis longitudinally for phenotype and repertoire, in order to determine which characteristics are most
predictive of the final antibody response. In Aim 2, we will compare subjects receiving adjuvanted HBV vaccine
to those receiving traditional HBV vaccine to determine how the cTfh and B cell responses differ due to
adjuvant, using multi-modality single cell profiling. Finally, in Aim 3, we will test mechanisms of how chronic
inflammation in the host affects the HBV vaccine response by performing direct lymph node biopsies for
multiplex immunofluorescence studies. Together, these experiments will explore the effects of repeated
antigen exposure, adjuvants, and chronic inflammation on the cTfh-B cell axis and suggest future strategies for
improved vaccine design.

## Key facts

- **NIH application ID:** 10490910
- **Project number:** 5R01AI158617-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Ramin Herati
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $791,641
- **Award type:** 5
- **Project period:** 2021-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490910

## Citation

> US National Institutes of Health, RePORTER application 10490910, A systems immunology approach for predicting poor responses to Hepatitis B vaccination (5R01AI158617-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10490910. Licensed CC0.

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