The incredible diversity and abundance of the human microbiome has only come to light in the last decade. The scientific community has learned that the gut microbial ecosystem has a major role in the development and homeostasis of the immune system. Our team wants to learn how these systems communicate to shape HIV vaccine immune responses. We are interested in how the microbiome shapes immune responses to HIV vaccines and contributes to vaccine response heterogeneity. We have a special emphasis on investigating the durability and class of antibodies that are elicited by different vaccines and the cellular responses that may contribute to these humoral endpoints, and how specific microbiota may contribute to these different responses. We will conduct correlates analyses with clinical and mouse microbiome and immunogenicity data; we will unravel mechanisms of immunity by perturbation of the immune system and the microbiome ? the immune system via multiple adjuvanted immunization regimens and the microbiome by gut microbial reconstitution in germ free mice; and we will conduct metabolomics case-control analyses from select human and mouse samples. The knowledge gained in the end will shed light on the mechanisms of how vaccines work and may improve vaccines by way of novel adjuvant discovery.

Public Health Relevance

This research project will investigate the microbial ecosystem inside our bodies and the role it has on how we respond to vaccines. We will first look at the very diverse populations in humans and mice and identify relationships between the immune system and this internal ecosystem of microbes. We will then investigate the actual mechanisms involved in how humans and mice develop vaccine responses. We will then identify molecules that could be used to help enhance these responses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI127100-03
Application #
9546487
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Malaspina, Angela
Project Start
2016-09-27
Project End
2021-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109