The association between antibody levels before and after 7-valent pneumococcal conjugate vaccine immunization and subsequent pneumococcal infection in chronic arthritis patients.

Johanna Nagel,Pierre Geborek,Tore Saxne,Jan-Åke Nilsson,Lennart Truedsson,Martin Englund,Meliha C Kapetanovic,Göran Jönsson,Ingemar F Petersson

doi:10.1186/s13075-015-0636-z

Johanna Nagel, Pierre Geborek + Show 7 more

Open Access

https://doi.org/10.1186/s13075-015-0636-z

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Abstract

IntroductionThe aim of present study is to inverstigate the association between antibody levels after vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) and subsequent serious pneumococcal infections in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients.MethodsA cohort of 497 patients (RA = 248 and SpA = 249) received a single dose of PCV7. At vaccination, patients were treated with methotrexate (MTX; n = 85), anti-tumour necrosis factor (anti-TNF) + MTX (n = 169), anti-TNF monotherapy (n = 158) and non-steroidal anti-inflammatory drugs (NSAIDs)/analgesics (n = 85). Antibody levels of serotypes 6B and 23B were analyzed before and 4 to 6 weeks after vaccination using standard enzyme-linked immunosorbent assay (ELISA). Serious pneumococcal infections (pneumonia/lower respiratory tract infection, meningitis, sepsis, septic arthritis) occurring within 4.5 years after vaccination were identified in the Skåne Healthcare Register using the International Classification of Diseases, tenth revision (ICD-10) codes. The association between post-vaccination antibody levels and protection against infections and determination of protective cutoff levels was explored using receiver operating characteristic (ROC) curves. Predictors of infection were studied using regression analyses.ResultsEighteen infections were registered in 15 patients before vaccination and 27 infections in 23 patients after vaccination. Patients with serious infections after vaccination had significantly lower post-vaccination antibody titres for both 6B (P = 0.04) and 23 F (P = 0.04). Post-vaccination antibody levels of at least 1.29 mg/L and 1.01 mg/L for 6B and 23, respectively, were associated with better protection from serious infections. Higher age, concomitant prednisolone but not MTX or anti-TNF were associated with such infections.ConclusionsPatients with more robust antibody responses after vaccination with pneumococcal conjugate vaccine were less likely to suffer from serious infections. High age and prednisolone at vaccination were associated with putative serious pneumococcal infections in this cohort.Trial registration numberEudraCT EU 2007-006539-29 and NCT00828997. Registered 23 January 2009.

Highlights

The aim of present study is to inverstigate the association between antibody levels after vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) and subsequent serious pneumococcal infections in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients
34% SpA patients were on non-steroidal anti-inflammatory drugs (NSAIDs) only, while no RA patient received these remedies without MTX or tumour necrosis factor (TNF)-inhibitors
One-third of all patients were treated with anti-TNF + MTX and anti-TNF as monotherapy, respectively

Summary

Introduction

The aim of present study is to inverstigate the association between antibody levels after vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) and subsequent serious pneumococcal infections in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients. One of them contains 23 capsular polysaccharides (PPV) that primarily induce a B celldependent immune response This type of vaccine prevents bacteraemia but does not efficiently protect the host against pneumococcal infection [3,4]. Conjugation of capsular polysaccharides with a highly immunogenic protein, that is a non-toxic diphtheria toxoid, induces a B and T cell response [5] resulting in mucosal immunity and effectively protects against vaccine serotypes that induce invasive pneumococcal disease, thereby at the same time reducing vaccine serotype carrier rates [6,7]. Since 2012, the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practice (ACIP) recommends immunisation with a single dose of 13valent pneumococcal conjugate vaccine followed by a dose of PPV to all adults with immunocompromised conditions [11]. The 2014 updated recommendations include use of both vaccines to all adults ≥65 years of age [12]

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