The Influence of a Conjugated Pneumococcal Vaccination on Plasma Antibody Levels against Oxidized Low-Density Lipoprotein in Metabolic Disease Patients: A Single-Arm Pilot Clinical Trial.

Ronit Shiri-Sverdlov,Inês Magro Dos Reis,Nele Vanhoutvin,Annick Vanclooster,Marit Westerterp,Ger H Koek,David Cassiman,Dennis M Meesters,Christoph J Binder,Tom Houben,Yvonne Oligschlaeger,Tim Hendrikx

doi:10.3390/antiox10010129

Abstract

As a mediator between lipid metabolism dysfunction, oxidative stress and inflammation, oxidized low-density lipoprotein (oxLDL) is a promising therapeutical target in a wide range of metabolic diseases. In mice, pneumococcal immunization increases anti-phosphorylcholine and oxLDL antibody levels, and reduces atherosclerosis, non-alcoholic steatohepatitis and Niemann–Pick disease burden. These findings suggest that pneumococcal vaccination may be a useful preventive and therapeutical strategy in metabolic disease patients. In this pilot clinical trial, our aim was to determine whether the administration of a pneumococcal vaccine increases anti-phosphorylcholine and anti-oxLDL antibody levels in metabolic disease patients. The following patients were enrolled: four patients with familial partial lipodystrophy (all women, mean age 32 years old); three familial hypercholesterolemia patients (one girl, two boys; mean age 13 years); and two Niemann–Pick type B (NP-B) patients (two men, mean age 37.5 years old). Participants received one active dose of a 13-valent conjugated pneumococcal vaccine (Prevenar 13) and were followed-up for four weeks. Four weeks after Prevenar 13 vaccination, no differences were observed in patients’ levels of anti-oxLDL IgM or IgG antibodies. In addition, we observed a reduction in anti-phosphorylcholine (anti-PC) IgM antibody levels, whereas no differences were observed in anti-PC IgG antibody titers. These findings indicate that Prevenar 13 vaccination does not induce an immune response against oxLDL in patients with metabolic diseases. Therefore, Prevenar 13 is not suited to target the metabolic disruptor and pro-inflammatory mediator oxLDL in patients.

Highlights

We analyzed whether a pneumococcal conjugate vaccine elicits an immune response against oxidized low-density lipoprotein (oxLDL) and/or PC in human metabolic disease patients
While patients displayed an appropriate IgM- and IgG-mediated immune response against the Prevenar 13 vaccine, Prevenar 13 vaccination did not increase antibody levels against oxLDL or PC in patients. These findings suggest that the Prevenar 13 vaccine is not a suitable tool to increase anti-oxLDL or PC antibodies in metabolic disease patients, and that alternative immunization strategies are needed in order to target oxLDL in humans
Depending on the oxidative reagents and mechanisms, different portions of LDL can be modified to different extents; as such, it is likely that a heterogeneous population of oxLDL coexists in living organisms at any given time

Summary

Introduction

The importance of a properly functioning lipid metabolism is illustrated by the disease burden tied to the wide array of known acquired and inherited lipid metabolic diseases. A considerable number of individuals are genetically predisposed to develop metabolic dysfunction, including familial hypercholesterolemia (FH), lipodystrophy (LPD) and Niemann–Pick (NP) disease patients. Regardless of the underlying etiology, patients with lipid metabolic dysfunctions are at high risk of developing non-communicable diseases such as type 2 diabetes, cardiovascular and liver disease and cancer, which are estimated to account for nearly 70% of premature deaths worldwide [2]. The development of preventive and therapeutic strategies targeting disorders of lipid metabolism and associated disease burden is of utmost importance for patients, clinicians and societies alike

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