# The Immunogenetics of Measles Immunity

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2020 · $510,764

## Abstract

PROJECT SUMMARY/ABSTRACT
This application is a request for continued funding for Years 24-28 of 5R01 AI033144, which is a highly
productive research program aimed at identifying genetic—and other—factors that explain inter-individual
variations in immune responses to live measles vaccine among otherwise healthy individuals. Measles is the
most contagious human disease and a leading cause of death in children globally, with over 254,928 cases
and 134,000 deaths reported worldwide in 2015. Large outbreaks continue to occur even in highly immunized
settings. From 2014 to 2016, the US reported 896 known measles cases, with the 2014 cases being the
highest number of cases since measles elimination in 2000. Of 159 measles cases reported to the CDC during
January–April 2015, 18% had received measles vaccine. While the vast majority of measles cases are due to
failure to receive vaccine, outbreaks have repeatedly revealed vaccine failure among individuals who have
received two doses of MMR. The current vaccine results in a failure rate of 2-10% after two doses, which
presents a critical public health conundrum. For this reason, our proposal focuses on identifying signatures of
measles immunity after a 3rd dose of MMR – focusing on signatures of high and low/non-response to measles
vaccine. In this proposal, we move from the narrower genetics-only approach (gene sequence) to the broader
systems biology approach (gene expression/regulation, other) in order to identify factors that together identify
and define innate and adaptive immune response signatures (i.e., the low and high dimensional data that
predict the immune outcomes of interest). Such an approach has not been previously used for measles
vaccine and will allow us to computationally model the integration of immunologic and “omic” data, in
combination with established network resources, to define the relationship between live measles vaccination
and human immune responses. To accomplish this, we propose the following Specific Aims: (1) A systems
biology study of innate immune responses; (2) A systems biology study of humoral B cell immune responses;
(3) A systems biology study of the interrelationships between innate and humoral immune responses. This
proposal is innovative and significant in that it will use novel causal mediation analytical approaches to
evaluate the effect of subject characteristics on genomics and immune response outcomes, as well as how
transcriptomic information mediates the link between subject characteristics and immune response outcomes.
Our work can lead to an enhanced understanding of innate and adaptive vaccine immunogenicity, potential
new understandings of the mechanisms underlying vaccine failure, novel information that could inform future
rational vaccine design, and the ability to “relate changes at the molecular level to global properties observed
within the biological system.”

## Key facts

- **NIH application ID:** 9890929
- **Project number:** 5R01AI033144-26
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Gregory A. Poland
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $510,764
- **Award type:** 5
- **Project period:** 1993-09-30 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890929

## Citation

> US National Institutes of Health, RePORTER application 9890929, The Immunogenetics of Measles Immunity (5R01AI033144-26). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9890929. Licensed CC0.

---

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