BRCA1/2 Flu Vaccine

Influenza Vaccine Study in BRCA1 or BRCA2 Carriers

To evaluate immune function in BRCA1/2 mutation carriers without cancer, specifically to determine whether immune function in healthy individuals with germline loss of function BRCA1/2 mutations, impacts overall immune health and fitness.

Study Overview

• Status: Recruiting
• Conditions: BRCA1 Mutation; BRCA2 Mutation
• Intervention / Treatment: Biological: Seasonal influenza vaccine

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Susan Domchek, MD; Phone Number: 215-615-3360; Email: susan.domchek@pennmedicine.upenn.edu
• Study Contact Backup: Name: Heather Symecko, MPH; Phone Number: 215-662-2770; Email: hsymecko@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Susan Domchek, MD; Phone Number: 215-615-3360; Email: susan.domchek@pennmedicine.upenn.edu
      • Contact: Heather Symecko, MPH; Phone Number: 215-662-2770; Email: hsymecko@pennmedicine.upenn.edu
      • Principal Investigator: Susan Domchek, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients 25 years and older, seen at Cancer Risk Evaluation Program (CREP) in the Perelman Center for Advanced Medicine with BRCA1 or BRCA2 mutation.

Description

Inclusion Criteria:

• Males and females
• Over age 25
• BRCA1 or BRCA2 pathogenic or likely pathogenic mutation
• No personal cancer history apart from non melanoma skin cancer, localized thyroid cancer, in situ cancers of any type
• Participants must sign the informed consent form

Exclusion Criteria:

• Are allergic to influenza vaccination
• Have received influenza vaccination within the past 6 months
• Require prednisone, methotrexate, or other immunosuppressing medications
• Have HIV infection
• Have a history of solid organ tumor or bone marrow transplant
• Require combination immunotherapy;
• Are on other studies requiring blood draws that might exceed 450 mL total during the period of the influenza vaccine study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate immune function in female BRCA1/2 mutation carriers without cancer following seasonal influenza vaccination	Analysis of the primary objective will depend on determination of the strain-specific neutralizing antibody titer change from day 0 to the last study visit, performed as the standard assay as described by the World Health Organization (WHO).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory analysis- phenotypic evaluation of B cell	Phenotypic evaluation of B and T cell responses to vaccine at each timepoint. Phenotypic analysis involves flow cytometry on peripheral blood mononuclear cells (PBMC) from all subjects (10 mL blood per subject).	2 years
Exploratory analysis - transcriptional evaluation	Transcriptional evaluation of B and T cell responses to vaccine on day 7-10 timepoint. Transcriptional analyses including quantitative real-time PCR (RT-qPCR) and RNA sequencing (RNAseq) may be performed on a subset of the study subjects on the day 7-10 time point.	2 years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Susan Domchek, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Centers for Disease Control and Prevention (CDC). Estimates of deaths associated with seasonal influenza --- United States, 1976-2007. MMWR Morb Mortal Wkly Rep. 2010 Aug 27;59(33):1057-62.
• Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ, Furman D, Shen-Orr S, Dekker CL, Swan GE, Butte AJ, Maecker HT, Davis MM. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015 Jan 15;160(1-2):37-47. doi: 10.1016/j.cell.2014.12.020.
• Mouw KW, Goldberg MS, Konstantinopoulos PA, D'Andrea AD. DNA Damage and Repair Biomarkers of Immunotherapy Response. Cancer Discov. 2017 Jul;7(7):675-693. doi: 10.1158/2159-8290.CD-17-0226. Epub 2017 Jun 19.
• Casanova JL, Abel L, Quintana-Murci L. Immunology taught by human genetics. Cold Spring Harb Symp Quant Biol. 2013;78:157-72. doi: 10.1101/sqb.2013.78.019968. Epub 2013 Oct 3.
• Lucas CL, Lenardo MJ. Identifying genetic determinants of autoimmunity and immune dysregulation. Curr Opin Immunol. 2015 Dec;37:28-33. doi: 10.1016/j.coi.2015.09.001. Epub 2015 Oct 2.
• Mak TW, Hakem A, McPherson JP, Shehabeldin A, Zablocki E, Migon E, Duncan GS, Bouchard D, Wakeham A, Cheung A, Karaskova J, Sarosi I, Squire J, Marth J, Hakem R. Brca1 required for T cell lineage development but not TCR loci rearrangement. Nat Immunol. 2000 Jul;1(1):77-82. doi: 10.1038/76950.
• Cheung AM, Hande MP, Jalali F, Tsao MS, Skinnider B, Hirao A, McPherson JP, Karaskova J, Suzuki A, Wakeham A, You-Ten A, Elia A, Squire J, Bristow R, Hakem R, Mak TW. Loss of Brca2 and p53 synergistically promotes genomic instability and deregulation of T-cell apoptosis. Cancer Res. 2002 Nov 1;62(21):6194-204.
• Herati RS, Reuter MA, Dolfi DV, Mansfield KD, Aung H, Badwan OZ, Kurupati RK, Kannan S, Ertl H, Schmader KE, Betts MR, Canaday DH, Wherry EJ. Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults. J Immunol. 2014 Oct 1;193(7):3528-37. doi: 10.4049/jimmunol.1302503. Epub 2014 Aug 29.
• Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med. 2000 Dec 4;192(11):1553-62. doi: 10.1084/jem.192.11.1553.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2019
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: June 16, 2020
• First Submitted That Met QC Criteria: July 31, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Actual): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 8, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: UPCC 11119; 834194 (Other Identifier: University of Pennsylvania Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No