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. 2014 Dec 1;59(11):1588-92.
doi: 10.1093/cid/ciu682. Epub 2014 Sep 11.

Treating progressive multifocal leukoencephalopathy with interleukin 7 and vaccination with JC virus capsid protein VP1

Mireia Sospedra  1 , Sven Schippling  1 , Sara Yousef  2 , Ilijas Jelcic  3 , Silvia Bofill-Mas  4 , Raquel Planas  1 , Jan-Patrick Stellmann  2 , Viktoria Demina  5 , Paola Cinque  6 , Robert Garcea  7 , Therese Croughs  8 , Rosina Girones  4 , Roland Martin  1
Affiliations

Treating progressive multifocal leukoencephalopathy with interleukin 7 and vaccination with JC virus capsid protein VP1

Mireia Sospedra et al. Clin Infect Dis. .

Abstract

Progressive multifocal leukoencephalopathy is a currently untreatable infection of the brain. Here, we demonstrate in 2 patients that treatment with interleukin 7, JC polyomavirus (JCV) capsid protein VP1, and a Toll-like receptor 7 agonist used as adjuvant, was well tolerated, and showed a very favorable safety profile and unexpected efficacy that warrant further investigation.

Keywords: IL-7; JC virus; VP1; progressive multifocal leukoencephalopathy.

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Figures

Figure 1.
Figure 1.
Treatment protocol (upper scheme). Dotted gray lines represent time points of recombinant human interleukin 7 (rhIL-7) injection (patient 1: days –2 and 5; patient 2: days –2 and 7), solid gray lines represent time points of VP1 injection in combination with imiquimod (patient 1: days 0 and 41; patient 2: days 0 and 43), and black solid line represents simultaneous injection of VP1 and rhIL-7 in combination with imiquimod (patient 1: day 12; patient 2: day 17). Day 0 is the day of the first VP1 injection. Subtle differences in schedule between the 2 patients were due to an intercurrent urinary tract infection in patient 2. A, JC polyomavirus (JCV) load in cerebrospinal fluid from patient 1 (left) and patient 2 (right), before and at different time points during and after treatment. The y-axis represents viral load expressed as viral genome copies/mL and the x-axis shows time in days. B, T2 magnetic resonance imaging (MRI) from patient 1 (left top row) and patient 2 (right top row) before treatment and 12 or 14 months after treatment. Contrast-enhanced T1W MRI in patient 1 (left bottom row) and in patient 2 (right bottom row) performed before and 40 days (patient 1) or 17 days (patient 2) after first VP1 injection. White arrows point at gadolinium contrast enhancement indicative of neuroinflammation in the areas of progressive multifocal leukoencephalopathic lesions in both patients. The inset in the image of patient 1 focuses on the bandlike gadolinium-contrast-enhancing lesion. C, Scripps neurological rating scale before treatment and 3 months and 12 or 14 months after treatment. D, JCV VP1–specific and tetanus toxoid–specific CD4+ T-cell responses before (month –1, white histograms), during (patient 1: days 12 and 41; patient 2: days 17 and 43; gray histograms), and after (day 84, black histograms) rhIL-7/JCV VP1 vaccination treatment. Proliferative responses were measured by 3H-thymidine incorporation assay. Mean ± SEM and statistical significance are shown. *P < .05, **P < .01, ***P < .001. Abbreviations: CSF, cerebrospinal fluid; GC, genome copies; IL-7, interleukin 7; JCPyV, JC polyomavirus; NA, not available; SI, stimulation index; SNRS, Scripps neurological rating scale; TT, tetanus toxoid.
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