Special Issue "Multiple Sclerosis and Its Complications: Clinical Trials"

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Clinical Immunology".

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editor

Special Issue Information

Dear Colleagues,

The World Health Organization (WHO) estimates that over 2.5 million people globally suffer from MS. With the present global population growing to an unprecedented height of 6.5 billion in 2005 and anticipated to reach 7.6 billion by 2020, the prevalence and onset of MS in children and particularly adults is expected to rise exponentially. It is estimated that approximately 400,000 people suffer from MS in the US, with 500,000 Europeans and 18,000 Australians also suffering the disease. There are different subtypes of the disease characterised by increasing severity; benign MS, relapse/remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS). According to the international Federation of MS Societies, the estimated breakdown of the four types of MS described above is as follows: benign MS (20%), RRMS (25%), SPMS (40%) and PPMS (15%).

The MS market is expected to more than double in value across the major markets from 2006 to reach $10.7 billion in 2019 and is one of the fastest growing CNS therapy areas. One of the drivers behind this growth is the uptake of specific drugs in interferon naïve patients. Despite the market’s growth the MS market is relatively immature with only 5 products specifically indicated for the disease.

The MS specific therapies that are currently on the market include

  • Schering AG’s Betaferon/Betaseron (interferon beta-1b)
  • Biogen’s Avonex (interferon beta-1a)
  • Teva’s Copaxone (glatiramer acetate)
  • Serono/Pfizer’s Rebif (interferon beta-1a)
  • Amgen/Serono’s Novantrone (mitoxantrone)

The current drugs available are extremely expensive costing up to $17,000 depending on the country. Due to the limited affordable treatment options, there is no effective therapy able to stop progression of disease (beta interferon-1a approved for delaying progression of MS) there is a very high unmet need in the MS market particularly in the following areas:

  • Altering / stopping disease progression
  • Inducing and maintaining remission
  • Improved drug delivery methods
  • Cheaper drugs / therapies

For improved MS treatments it is relatively weak as compared to other CNS disorders, although there are a number of different drug classes in development including;

  • Monoclonal Antibodies - to block destructive immune cells entering brain and spinal cord
  • Immunosuppressant’s - suppress immune system and prevent myelin damage
  • Potassium channel blockers - improve the conduction of demyelinated fibers
  • Protein growth factors - to limit demyelination and oligodendrocyte injury
  • Immunotherapy / Vaccines - to switch immune response to protect neurons and prevent demyelination

This special issue is now open and is seeking research papers and reviews on MS human clinical studies.

Prof. Dr. Vasso Apostolopoulos
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Multiple sclerosis
  • Clinical trials
  • Vaccines
  • Altered peptide ligands
  • Immune therapies
  • Monoclonal Antibodies
  • Immunosuppressants
  • Growth Factors
  • Potassium channel blockers
  • Toxicology
  • Side effects
  • Tolerance
  • Peptides
  • Delivery systems
  • Particulate vaccines
  • Natural products
  • Anti-inflammatories

Published Papers (4 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Article
An Absence of Epstein–Barr Virus Reactivation and Associations with Disease Activity in People with Multiple Sclerosis Undergoing Therapeutic Hookworm Vaccination
Vaccines 2020, 8(3), 487; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8030487 - 28 Aug 2020
Viewed by 1350
Abstract
Background: Epstein–Barr virus (EBV) infection is strongly associated with multiple sclerosis (MS). Helminth infection can downregulate antiviral immune responses, potentially protecting against MS, but with a theoretical risk for reactivating latent EBV infection. Objective: To investigate parameters of EBV infection and their relationship [...] Read more.
Background: Epstein–Barr virus (EBV) infection is strongly associated with multiple sclerosis (MS). Helminth infection can downregulate antiviral immune responses, potentially protecting against MS, but with a theoretical risk for reactivating latent EBV infection. Objective: To investigate parameters of EBV infection and their relationship with disease activity in people with MS (PwMS) therapeutically vaccinated with Necator americanus (hookworm). Methods: Sequential serum samples from 51 PwMS; 26 therapeutically infected (25 larvae) with N. americanus and 25 controls were tested for EBV virus capsid antigen (VCA) IgG and IgM, EBV nuclear antigen-1 (EBNA-1) IgG, and EBV early antigen (EA) IgG. Disease activity was assessed by periodic MRI. Significance was set at p < 0.05. Results: All PwMS were EBV VCA IgG and EBNA-1 IgG positive, and 35.2% were EBV EA IgG positive. EBV antibody levels were generally stable, and EBV reactivation in PwMS was not demonstrated by significant increases in IgG titre over 12 months. Disease activity was most frequent in PwMS possessing high levels of EBV VCA IgG (>600 units/mL) or EBNA-1 IgG (>150 units/mL); however, there was no association with hookworm treatment. Interpretation: Therapeutic hookworm vaccination was not associated with EBV reactivation. Multiple sclerosis disease activity was associated with high levels of EBV VCA IgG or EBNA-1 IgG. Full article
(This article belongs to the Special Issue Multiple Sclerosis and Its Complications: Clinical Trials)
Show Figures

Figure 1

Review

Jump to: Research

Review
Multiple Sclerosis and SARS-CoV-2 Vaccination: Considerations for Immune-Depleting Therapies
Vaccines 2021, 9(2), 99; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9020099 - 28 Jan 2021
Cited by 10 | Viewed by 1792
Abstract
Several concerns have been raised about the use of immunodepleting agents including alemtuzumab, cladribine and CD20-depleting antibodies in people with multiple sclerosis (pwMS) during the coronavirus disease (COVID) 2019 pandemic. As the end of the pandemic is not yet in sight, vaccination against [...] Read more.
Several concerns have been raised about the use of immunodepleting agents including alemtuzumab, cladribine and CD20-depleting antibodies in people with multiple sclerosis (pwMS) during the coronavirus disease (COVID) 2019 pandemic. As the end of the pandemic is not yet in sight, vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) may be an elegant strategy to overcome the potential hazards associated with initiating and continuing treatment with immune-depleting agents. In this review, we summarize the immunological effects of immune-depleting therapy and underlying considerations for the hitherto existing recommendations that suggest a restricted use of immune-deleting therapies during the pandemic. Moreover, we critically discuss open questions regarding vaccination in general and against SARS-CoV-2 in pwMS. Full article
(This article belongs to the Special Issue Multiple Sclerosis and Its Complications: Clinical Trials)
Show Figures

Figure 1

Review
Safety of Newer Disease Modifying Therapies in Multiple Sclerosis
Vaccines 2021, 9(1), 12; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9010012 - 26 Dec 2020
Cited by 1 | Viewed by 2202
Abstract
In the past decade, the therapeutic arsenal for multiple sclerosis has expanded greatly. Newer more potent disease modifying therapies (DMTs) with varying mechanisms of actions are increasingly used early in the disease course. These newer DMTs include oral therapies (teriflunomide, dimethyl fumarate, fingolimod, [...] Read more.
In the past decade, the therapeutic arsenal for multiple sclerosis has expanded greatly. Newer more potent disease modifying therapies (DMTs) with varying mechanisms of actions are increasingly used early in the disease course. These newer DMTs include oral therapies (teriflunomide, dimethyl fumarate, fingolimod, siponimod, ozanimod, and cladribine) and infusion therapies (natalizumab, alemtuzumab, and ocrelizumab), and are associated with better control of disease activity and long-term outcomes in patients with MS compared to older injectable therapies (interferon beta and glatiramer acetate). However, they are associated with safety concerns and subsequent monitoring requirements. Adverse events are initially observed in phase 2 and 3 clinical trials, and further long-term data are collected in phase 3 extension studies, case series, and post-marketing reports, which highlight the need to periodically re-evaluate and adjust monitoring strategies to optimize treatment safety in an individualized approach. Full article
(This article belongs to the Special Issue Multiple Sclerosis and Its Complications: Clinical Trials)
Review
Infections, Vaccines and Autoimmunity: A Multiple Sclerosis Perspective
Vaccines 2020, 8(1), 50; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8010050 - 28 Jan 2020
Cited by 14 | Viewed by 2479
Abstract
Background: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that is associated with multiple environmental factors. Among suspected susceptibility events, studies have questioned the potential role of overt viral and bacterial infections, including the Epstein Bar virus (EBV) and human endogenous [...] Read more.
Background: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that is associated with multiple environmental factors. Among suspected susceptibility events, studies have questioned the potential role of overt viral and bacterial infections, including the Epstein Bar virus (EBV) and human endogenous retroviruses (HERV). Furthermore, the fast development of immunomodulatory therapies further questions the efficacy of the standard immunization policies in MS patients. Topics reviewed: This narrative review will discuss the potential interplay between viral and bacterial infections and their treatment on MS susceptibility and disease progression. In addition, the review specifically discusses the interactions between MS pathophysiology and vaccination for hepatitis B, influenza, human papillomavirus, diphtheria, pertussis, and tetanus (DTP), and Bacillus Calmette-Guerin (BCG). Data regarding potential interaction between MS disease modifying treatment (DMT) and vaccine effectiveness is also reviewed. Moreover, HERV-targeted therapies such as GNbAC1 (temelimab), EBV-based vaccines for treatment of MS, and the current state regarding the development of T-cell and DNA vaccination are discussed. Lastly, a reviewing commentary on the recent 2019 American Academy of Neurology (AAN) practice recommendations regarding immunization and vaccine-preventable infections in the settings of MS is provided. Conclusion: There is currently no sufficient evidence to support associations between standard vaccination policies and increased risk of MS. MS patients treated with immunomodulatory therapies may have a lower benefit from viral and bacterial vaccination. Despite their historical underperformance, new efforts in creating MS-based vaccines are currently ongoing. MS vaccination programs follow the set back and slow recovery which is widely seen in other fields of medicine. Full article
(This article belongs to the Special Issue Multiple Sclerosis and Its Complications: Clinical Trials)

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Infections, Vaccines and Autoimmunity: Multiple Sclerosis Perspective
Authors: Dejan Jakimovski; Bianca Weinstock-Guttman; Murali Ramanathan; Michael G. Dwyer; Robert Zivadinov
Affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY, USA;
Abstract: Background: Multiple sclerosis (MS) is chronic neuroinflammatory and neurodegenerative disease associated with multiple environmental factors. Among suspected susceptibility events, studies have questioned the potential role of overt viral and bacterial infections including Epstein Bar virus (EBV) and human endogenous retroviruses (HERV). Furthermore, the fast development of immunomodulatory therapies further questions the efficacy of the standard immunization policies in MS patients. Topics reviewed: This narrative review will discuss the potential interplay between viral and bacterial infections and their treatment on MS susceptibility and disease progression. In addition, , the review specifically discusses the interactions between MS pathophysiology and vaccination for hepatitis B, influenza, human papillomavirus, diphtheria, pertussis and tetanus (DTP), and Bacillus Calmette-Guerin (BCG). Data regarding potential interaction between MS disease modifying treatment (DMT) and vaccine effectiveness is also reviewed. Moreover, HERV-targeted therapies such as GNbAC1 (temelimab), EBV-based vaccines for treatment of MS, and the current state regarding the development of T-cell and DNA vaccination are discussed. Lastly, a reviewing commentary on the recent 2019 American Academy of Neurology (AAN) practice recommendations regarding immunization and vaccine-preventable infections in the settings of MS is provided. Conclusion: There are currently no sufficient evidence to support associations between standard vaccination policies and increased risk of MS. MS patients treated with immunomodulatory therapies may have a lower benefit from viral and bacterial vaccination. Despite their historical underperformance, new efforts in creating MS-based vaccines are currently ongoing. MS vaccination programs follow the set back and slow recovery which is widely seen in other fields of medicine.

Back to TopTop