2193. Immune Profiling of Coxiella burnetii Infection by Mass Cytometry
Session: Poster Abstract Session: Host-Pathogen Interactions
Saturday, October 29, 2016
Room: Poster Hall
Background:

Coxiella burnetii (Cb), is a highly infectious and stable bacteria that causes Q-fever in humans. Treatment for Q-fever can require months of antibiotics; therefore, vaccination is considered critical to infection control. The currently available vaccine may induce severe reactogenicity in previously exposed patients. The Q-VaxCelerate consortium project aims to develop a safe, effective, and less reactogenic Q-fever vaccine.

Methods:

To characterize the immune response to Cb infection or vaccination in both human and mouse samples we developed an approach utilizing Cytometry by Time Of Flight mass spectrometry (CyTOF) to measure >35 immune-parameters simultaneously. Using CyTOF we measured a broad array of cell populations, activation makers, and cytokines in both human and murine samples. Donors were recruited from a region that experienced an outbreak of Q-fever (2007-2009) and we determined pre-existing immunity against Cb by measuring anti-Cb antibody titres and IFNg production. Blood from characterized donors was stimulated with killed Cb and analyzed by flow cytometry and CyTOF. To measure the immune response during infection, naïve mice were challenged with Cband blood samples were collected prior to and during challenge over 35 days.

Results: Cb exposed patients exhibited increased IFNg, TNFa, and IL-1b expression in T-cells, NK cells, and macrophages. CyTOF analysis of murine samples indicated early increases of innate immune cell numbers and activation, including increased expression of TGFb. Late during infection, days 24 and 35, CD8 T-cells increased expression of IL-2, IL-6, and IL-10. Together these data reveal novel hallmarks of the immune response during and following infection. Ongoing animal studies will characterize the immune response in vaccinated mice upon challenge with Cb. We continue to recruit and characterize human donors, working to assess immune responses across a diversity of HLA types and clinical responses. Analysis of cell sub-types from both human and mouse samples remains underway.

Conclusion: The data from completed and ongoing studies will be used to generate immune signatures that facilitate the testing and evaluation of candidate vaccines for Cb and may lead to insights on the diversity of patient outcomes following Cb infection.

Patrick Reeves, PhD1, Susan Raju Paul, MBBS2, Lenny Moise, PhD3, Carl Pierce, BS2, Luijkx Thomas, PhD4, Anja Garritsen, PhD4, Laurie Baeten, DVM5, Richard Bowen, DVM PhD5, Jeffrey Gelfand, MD, FIDSA6, Annie De Groot, MD3, Timothy Brauns, MBA2, Ann Sluder, PhD2 and Mark Poznansky, MD, PhD2, (1)Infectious Disease, Massachusetts General Hospital, Charlestown, MA, (2)Massachusetts General Hospital, Charlestown, MA, (3)EpiVax, Providence, RI, (4)InnatOss, Oss, Netherlands, (5)Colorado State University, Ft. Collins, CO, (6)Medicine, Massachusetts General Hospital, Boston, MA

Disclosures:

P. Reeves, None

S. Raju Paul, None

L. Moise, EpiVax: Employee , Salary

C. Pierce, None

L. Thomas, None

A. Garritsen, InnatOss: Board Member and Employee , Salary

L. Baeten, None

R. Bowen, None

J. Gelfand, None

A. De Groot, EpiVax: Board Member and Employee , Salary

T. Brauns, None

A. Sluder, None

M. Poznansky, None

Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.