# The "Dynamics of the immune responses to repeat influenza vaccination exposures" (DRIVE) Study

> **NIH NIH U01** · UNIVERSITY OF CHICAGO · 2022 · $1,223,323

## Abstract

PROJECT SUMMARY
Annual vaccination remains the primary public health strategy to mitigate the burden of influenza infection, and
there is evidence that repeated influenza vaccination can affect the efficacy of the vaccine. This evidence arises
not only from multiple observational studies of vaccine effectiveness but also studies of immunogenicity,
including small trials. Understanding what causes influenza vaccines to be more or less effective in different
people and populations is critical to the rational deployment of existing vaccines and the development of universal
vaccines. But the causes of altered effectiveness and immunogenicity in repeat vaccinees are intrinsically difficult
to study in populations in which vaccination is universally recommended, because repeat vaccinees differ from
other vaccinees and non-vaccinees in important ways. These differences leave open the possibility of residual
confounding in infection and vaccination history, and thus make it difficult to identify the effects of vaccination
itself. We propose a randomized, clinical trial to investigate the effects of repeat vaccination and their underlying
immunological causes in an adult population with low vaccination coverage and no recommendation for influenza
vaccination. Approximately 820 adults in Hong Kong will be randomized into five groups, with one group
vaccinated the first year, and other groups receiving placebo (saline) injections; each year, another group will
start receiving the influenza vaccine, and will be vaccinated annually until the study ends after four years. This
design will allow comparison of vaccine responses and failures (infections) in the placebo, newly vaccinated,
and repeatedly vaccinated participants. Additionally, it will provide longitudinal samples of immune status and
influenza-specific responses over time, from which we will develop predictive models of the response to
vaccination and infection, including repeat vaccination. The proposed high-dimensional immunological profiling,
coupled with statistical approaches that can accommodate the complexity of the key hypotheses, should
maximize insight into the effects of repeated vaccination on seasonal influenza. The models will formalize,
evaluate, and extend current theory, and thus provide a quantitative basis for anticipating vaccine non-
responsiveness and improving vaccination strategies. Banked specimens will enable new hypotheses to be
tested in the future.

## Key facts

- **NIH application ID:** 10426322
- **Project number:** 5U01AI153700-03
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** BENJAMIN JOHN COWLING
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,223,323
- **Award type:** 5
- **Project period:** 2020-09-11 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426322

## Citation

> US National Institutes of Health, RePORTER application 10426322, The "Dynamics of the immune responses to repeat influenza vaccination exposures" (DRIVE) Study (5U01AI153700-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10426322. Licensed CC0.

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