2024 Recipient of the Lupus Canada Catalyst Award

Researcher 

Arielle Mendel, MD, MSc 

Research Proposal Abstract 

Herpes zoster (HZ) is a preventable adverse event affecting 1 in 3 patients with systemic lupus erythematosus (SLE). HZ in SLE can lead to hospitalization, chronic pain, and reduced quality of life. The two-dose adjuvanted recombinant zoster vaccine (RZV, Shingrix) is recommended in SLE, but many questions remain on how to optimize HZ prevention. Common immunosuppressants in SLE increase HZ risk, but may also impair immune responses to RZV. Safety of the RZV during periods of disease activity (a high risk period for HZ) is uncertain. 

The REcombinant herpes ZostER Vaccination in Systemic Lupus Erythematosus (REZERV-SLE) study aims to evaluate unanswered questions on: 

1. The uptake of the RZV in SLE 
2. The safety of RZV in terms of SLE flares 
3. The humoral immune responses to RZV across age groups and medication exposures 

We will study two large prospective SLE research cohorts who undergo annual standardized data collection, including clinical data (demographics, medication exposures, vaccinations, disease activity, and damage, patient reported outcomes) and serum sample biobanking. Firstly, we will evaluate vaccination patterns before and after implementing a free provincial vaccination program for immunocompromised patients. 

Among cohort participants eligible for vaccination as of October 2017 (first availability) and May 2023 (first free availability in Quebec), we will assess the proportion vaccinated for HZ and perform survival analyses to assess characteristics (demographic, clinical) associated with vaccination. We will also determine the proportion who received a second dose any time in the subsequent 12 months. Using a 1) self-controlled case series design and 2) survival analyses, we will determine if RZV vaccination is associated with increased risk of SLE flares. 

Finally, we will assess humoral immune responses to RZV within previously banked serum collected from 40 cohort participants before and after vaccination, using an anti-Varicella Zoster Virus glycoprotein E enzyme-linked immunosorbent assay. We will explore whether immune responses differ according to age and medication exposures (e.g. mycophenolate, prednisone) at the time of vaccination. Our team brings expertise in lupus, vaccination, epidemiology, public health, immunology, and quality improvement, positioning us for success. 

Our proposal addresses an important preventable adverse event in SLE. Identifying current patterns of RZV uptake in SLE will help us to identify gaps and develop benchmarks. By harnessing data and samples collected within large SLE cohorts, we will provide some of the very first data on RZV safety and efficacy in SLE, which we will use to design future prospective studies in this vulnerable group. 

Layperson Summary 

Shingles is a painful blistering rash caused by reactivation of the varicella (chickenpox) virus. Because people with systemic lupus erythematosus (SLE) have altered immune function and take immunosuppressants, they are up to 5 times more likely to get shingles than people without lupus, and at a much younger age. Shingles in lupus can also be more severe. A 2-dose vaccine (Shingrix), recommended to prevent shingles in SLE, is now available free of charge to immunocompromised people in Quebec. We do not yet know what proportion of people living with lupus get vaccinated, or even how well this vaccine works in lupus, and although it is very safe, some patients may be concerned that the vaccine could trigger lupus flares. 

Our proposal will answer 3 questions: 

1. What proportion of patients with lupus get the shingles vaccine as recommended? 
2. Is shingles vaccination associated with lupus flares? 
3. Do people with lupus mount good immune responses to the vaccine? 

We will study 700 people with lupus from two research cohorts in Quebec who have yearly research visits and blood sample collections. We will determine what proportion have been vaccinated for shingles, and examine if there are groups who are less likely to get vaccinated, and/or less likely to receive both doses. 

To assess whether shingles vaccination could trigger lupus flares, we will use methods to compare flare rates during periods exposed and unexposed to the vaccine. Finally, we will test blood samples collected from cohort participants before and after vaccination, to measure how well people with lupus produce protective antibodies to the vaccine, including years down the road. Our team includes experts in SLE and vaccination in immunocompromised populations, as well as a patient with lupus.