Natalizumab treatment shows no clinically meaningful effects on immunization responses in patients with relapsing-remitting multiple sclerosis

Kaufman, Michael D.; Pardo, Gabriel; Rossman, Howard; Sweetser, Marianne T.; Forrestal, Fiona; Duda, Petra W.

doi:10.1016/j.jns.2014.03.035

Cited by 74 publications

(63 citation statements)

References 21 publications

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“…We reported lower protection rates during natalizumab therapy in our previous study using the HI method in 17 patients vaccinated during 2009/2010 sampled at 10 months and in 8 patients vaccinated in 2010/2011 sampled at 6 months . Others have, however, found unchanged protection if vaccinated with a strongly immunogenic protein but not an influenza antigen in 30 patients sampled at 28 and 56 days post‐vaccination and measured by enzyme‐linked immunosorbent assay . Another study reported reduced vaccine response to influenza A but not to influenza B compared with controls, which is compatible with our results.…”

Section: Discussionsupporting

confidence: 91%

Antibody response to seasonal influenza vaccination in patients with multiple sclerosis receiving immunomodulatory therapy

Olberg

Eide

Cox

et al. 2018

Euro J of Neurology

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Section: Discussionsupporting

confidence: 91%

Antibody response to seasonal influenza vaccination in patients with multiple sclerosis receiving immunomodulatory therapy

Olberg

Eide

Cox

et al. 2018

Euro J of Neurology

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“…Thus, the availability of safe and effective measures for preventing PML could significantly increase the overall safety profiles of therapies for a wide variety of autoimmune diseases and lymphoid cancers. This would be particularly true for immunomodulatory therapies, such as natalizumab, that are compatible with vaccination (44). …”

Section: Discussionmentioning

confidence: 99%

JC polyomavirus mutants escape antibody-mediated neutralization

et al. 2015

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JC polyomavirus (JCV) persistently infects the urinary tract of a majority of adults. Under conditions of immune impairment, JCV causes an opportunistic brain disease, progressive multifocal leukoencephalopathy (PML). JCV strains found in the cerebrospinal fluid (CSF) of PML patients contain distinctive mutations in surface loops of the major capsid protein, VP1. We hypothesized that VP1 mutations might allow the virus to evade antibody-mediated neutralization. Consistent with this hypothesis, neutralization serology revealed that plasma samples from PML patients neutralized wild-type JCV strains but failed to neutralize patient-cognate PML-mutant JCV strains. This contrasted with serological results for healthy individuals, most of whom robustly cross-neutralized all tested JCV variants. Mice administered a JCV virus-like particle (VLP) vaccine initially showed neutralizing “blind spots” (akin to those observed in PML patients) that closed after booster immunization. A PML patient administered an experimental JCV VLP vaccine likewise showed dramatically increased neutralizing titer against her cognate PML-mutant JCV. The results indicate that deficient humoral immunity is a common aspect of PML pathogenesis and that vaccination may overcome this humoral deficiency. Thus, vaccination with JCV VLPs might prevent the development of PML.

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“…It remains enigmatic which of the 2 adhesion molecules, VLA‐4 or LFA‐1 of plasma cells, is providing the essential survival signal, and how it is acting in the plasma cells to prevent apoptosis, or whether both are redundant. It should be noted that inhibition of CD49d alone, by the therapeutic antibody Natalizumab, neither affected the generation nor the maintenance of humoral memory in secondary immune reactions to vaccines in patients with systemic sclerosis 38. Neither did it decrease Aquaporin‐4‐specific autoantibody titers in patients with neuromyelitis optica spectrum disorders.…”

Section: Conditional Survival Of Memory Plasma Cells—the Memory Nichementioning

confidence: 94%

“…It should be noted that inhibition of CD49d alone, by the therapeutic antibody Natalizumab, neither affected the generation nor the maintenance of humoral memory in secondary immune reactions to vaccines in patients with systemic sclerosis. 38 Neither did it decrease Aquaporin-4-specific autoantibody titers in patients with neuromyelitis optica spectrum disorders. Those autoantibodies were presumably derived from established memory plasma cells, at least in those patients who before or afterwards were refractory to Rituximab.…”

Section: Conditional Survival Of Memory Pl a S Ma Cell S-the Memorymentioning

confidence: 96%

Immunological memories of the bone marrow

Chang

Tokoyoda

Radbruch

2018

Immunological Reviews

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SummaryMemory for antigens once encountered is a hallmark of the immune system of vertebrates, providing us with an immunity adapted to pathogens of our environment. Despite its fundamental relevance, the cells and genes representing immunological memory are still poorly understood. Here we discuss the concept of a circulating, proliferating, and ubiquitous population of effector lymphocytes vs concepts of resting and dormant populations of dedicated memory lymphocytes, distinct from effector lymphocytes and residing in defined tissues, particularly in barrier tissues and in the bone marrow. The lifestyle of memory plasma cells of the bone marrow may serve as a paradigm, showing that persistence of memory lymphocytes is not defined by intrinsic “half‐lives”, but rather conditional on distinct survival signals provided by dedicated niches. These niches are organized by individual mesenchymal stromal cells. They define the capacity of immunological memory and regulate its homeostasis.

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Natalizumab treatment shows no clinically meaningful effects on immunization responses in patients with relapsing-remitting multiple sclerosis

Cited by 74 publications

References 21 publications

Antibody response to seasonal influenza vaccination in patients with multiple sclerosis receiving immunomodulatory therapy

Antibody response to seasonal influenza vaccination in patients with multiple sclerosis receiving immunomodulatory therapy

JC polyomavirus mutants escape antibody-mediated neutralization

Immunological memories of the bone marrow

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