Immunogenicity of recombinant zoster vaccine in Rheumatoid arthritis patients

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Rheumatoid arthritis (RA) is the most common inflammatory arthritis with a prevalence of around 0.6% in the general population and is a common chronic autoimmune disease in the veteran population. RA patients suffer greater mortality and morbidity from infectious diseases. This increased burden is in part related to the immune derangements of RA itself, and some of it is attributable to the immunosuppressive therapies that are used to treat RA. Herpes Zoster (HZ) reactivation is the most common opportunistic infection of treated RA patients and is about double that of the general population. HZ already has a lifetime risk of 20-30% in the general population. Until the recent approval of a recombinant zoster vaccine (RZV, brand name Shingrix) there was only the live attenuated vaccine, Zostavax. It was infrequently used in RA patients on treatment due to its contraindication in immunosuppressed individuals as it is a live virus vaccine. RZV being a subunit vaccine does not have this limitation. In addition, RZV has been found in the general adult population to be highly efficacious (>90%) even in persons over age 80. This has resulted in a significant potential opportunity to protect RA patients even on immunosuppressive therapy. Immune protection from HZ is much different than immunity to primary varicella zoster (VZV) infection (chickenpox) which is primarily antibody-mediated. Work from an innovative primate model of HZ suggests that cell-mediated immunity (CMI), specifically by CD4+ T cells, is a key for protection. All of the vaccines previously studied in RA patients have been ones that elicit protection through antibody-mediated mechanisms and not CMI. The effect of disease-modifying antirheumatic drugs (DMARDs) on vaccine immunogenicity or efficacy, in particular focused on RZV elicitation of CMI is not known. The proposed study is therefore innovative, in that they propose to determine the effect of RA and DMARD treatment on the immunogenicity of RZV. Analysis of response to RZV in RA patients proposed in this study has direct clinical relevance and translational potential. It may influence the choices of DMARDs to be utilized as there are many options for treating RA. It could provide data that supports a clinical trial using drug windowing where the treatment with DMARD is withheld transiently after vaccination to improve the response. They hypothesize that RZV will have a reduced immunogenicity in RA patients compared to non-RA controls and that RA patients on anti-metabolite synthetic DMARDs will have reduced immunogenicity more than those on biologic DMARDs such as TNFi. They will perform a laboratory blinded observational study of 100 RA patients, the overwhelming majority of whom are on DMARDs, and 100 age-matched non-rheumatology subjects to determine the difference in immunogenicity of RZV between these populations. Specific Aims: Aim 1. To determine the magnitude and differential effects of synthetic and biologic DMARD therapies on the immunogenicity of RZV in RA patients. Aim 2 To determine the mechanistic pathways of both reduced and robust vaccine specific responses to RZV using systems biology approaches and to determine the signatures that is associated with these responses in RA patients on DMARDS. Aim 3. To compare adverse event profile of RZV vaccination in RA patients to age-matched non- rheumatic disease individuals.