Flu vaccination with a virosomal vaccine does not affect clinical course and immunological parameters in scleroderma patients

Abstract

Safety and efficacy of adjuvanted vaccines in autoimmune individuals raises growing clinical and scientific interest. Protection from influenza would bring particular benefits in these patients with common cardiac and respiratory impairment. This study evaluates efficacy, clinical safety and immune effects of the administration of a single dose of a virosomal flu vaccine in 46 scleroderma patients. The following parameters were evaluated before and after administration of Inflexal: clinical conditions, inflammation and autoimmunity parameters, humoral response, lymphocyte proliferation and cytokine production upon flu antigen stimulation by specific and non-specific cells. Inflexal was found effective in scleroderma patients. In no subject was worsening of clinical conditions, inflammation and immunological parameters observed.

Introduction

Connective tissue diseases (CTD) are chronic autoimmune inflammations with common involvement of lower respiratory tract. These features are characteristic of several pathological conditions, such as Progressive Systemic Sclerosis (or Scleroderma - PSS), Mixed Connective Tissue Disease, Rheumatoid Arthritis and Overlapping Syndrome. Interstitial lung disease may start early in the course of the main syndrome and cause defect in blood oxygenation, pulmonary hypertension, right cardiac chamber hypertrophy/dilatation, respiratory and/or circulatory failure.

Superimposed infections, especially if respiratory, may exacerbate the course of the disease, accelerate cardiac involvement, cut therapeutic options. Iatrogenic damage to host defences due to immunosuppressive treatment may further enhance the extent of risk. Autoimmune patients may then take benefit from several vaccinations, especially influenza and pneumococcal, independently on their belonging to other risk groups.

However, little is known about response to vaccines in autoimmune individuals. There are some suggestions that the intrinsic abnormalities of their immune system and/or the immunosuppressive treatments received may hamper the capacity of these patients of properly responding to vaccine immunization, as well as to natural infections themselves [1], [2]. The desired antinfective protection after vaccination may not been achieved completely or at all. Indeed, studies aimed at testing both humoral and cellular response to vaccinations in CTD patients are limited.

On the other hand, the spreading use of prophylactic vaccinations both in infants and in adults has been recently attacked by several movements against vaccines. In fact, one of their major concern seems to be that vaccinations may induce a broad spectrum of adverse immune manifestations such as autoimmune or immune mediated diseases. No scientific data other than precarious, sometimes picaresque theoretical hypotheses or anecdotal observations have ever been produced in support of the totality of those claims, but in a few particular, extremely rare situations [3], [4], [5]. Besides, in the ground of theoretical hypotheses, several exist as well to explain why autoimmunity after vaccination does not actually occur. Furthermore, should a pressure be exerted by a certain vaccination toward autoimmunity, a much more powerful risk would exist from the natural infection itself: even for the most imputable vaccines, triggering of autoimmunity by vaccination in protected individuals remains inferior than triggering of autoimmunity by the disease occurring in non-protected ones, so that there should be little doubt about the large advantage of vaccination programs versus preserving the natural history of infections.

Nevertheless, vaccines, especially if adjuvanted, do possess a theoretical potential for interfering with immune response in an autoreactive way. Most adjuvants have been recently discovered to act as ligands of innate immunity Toll-like receptors or at least stimulators of innate immunity mechanisms [6], [7], [8], [9]. These interactions enhance and direct the immune response upon contact with the antigen. Pushing theory to an edge, the administration of molecules with stimulating effects in the sense of a potent Th1 response, together with antigens at risk for molecular mimicry, could trigger an autoimmune cross-reactive response in a subject genetically prone to autoimmunity.

Some influenza vaccines on the market in our country have been prepared to enhance immunogenicity in those patients in which they are particularly useful but also less successful, such as elderly individuals [10], [11], [12], [13], [14]. They contain different adjuvant systems and may fit the profile of potentially dangerous vaccines. Clinicians have been reassured by reports from several epidemiological studies which failed to identify any conversion of such potential into clinical events, denying any causal relationship between certain immunizations and some clinical events observed afterwards [3], [5], [15], [16]. Indeed, it is also true that very few prospective studies, if any, were specifically designed with the aim of investigating safety and efficacy of vaccines in autoimmune subjects.

To contribute to fill this gap, in the present work the effects of a virosomal influenza vaccine on several experimental and clinical parameters, significant for the assessment of the disease status, were tested after administration to patients affected by PSS, a paradigmatic condition of autoimmunity.