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Current Opinion in Virology Apr 2020Over the last years, the development of viruses to treat cancer patients has re-gained considerable attention. A genetically modified herpesvirus, Talimogene... (Review)
Review
Over the last years, the development of viruses to treat cancer patients has re-gained considerable attention. A genetically modified herpesvirus, Talimogene laherparepvec, has already been authorized for the treatment of melanoma patients. Also recombinant measles virus (MeV) is developed as an oncolytic virus. Because of its high genetic flexibility, a number of different MeV strains have been the basis for the generation of targeted, armed, or shielded viruses that are highly specific for a given tumor target, more effective, or protected against serum neutralization. Such MeV have been extensively tested in vitro and in vivo, whereby remarkable oncolytic potency is accompanied by safety also in non-human primates. Therefore, MeV has been introduced into 19 different clinical trials and has reached phase II against two different tumor entities, multiple myeloma and ovarian carcinoma. Remarkably, one patient with advanced stage myeloma experienced long-term remission after treatment, visualizing the potency of this approach.
Topics: Animals; Humans; Measles virus; Melanoma; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 32861945
DOI: 10.1016/j.coviro.2020.07.016 -
Journal of Medical Virology Nov 2021Virus invasion activates the host's innate immune response, inducing the production of numerous cytokines and interferons to eliminate pathogens. Except for viral... (Review)
Review
Virus invasion activates the host's innate immune response, inducing the production of numerous cytokines and interferons to eliminate pathogens. Except for viral DNA/RNA, viral proteins are also targets of pattern recognition receptors. Membrane-bound receptors such as Toll-like receptor (TLR)1, TLR2, TLR4, TLR6, and TLR10 relate to the recognition of viral proteins. Distinct TLRs perform both protective and detrimental roles for a specific virus. Here, we review viral proteins serving as pathogen-associated molecular patterns and their corresponding TLRs. These viruses are all enveloped, including respiratory syncytial virus, hepatitis C virus, measles virus, herpesvirus human immunodeficiency virus, and coronavirus, and can encode proteins to activate innate immunity in a TLR-dependent way. The TLR-viral protein relationship plays an important role in innate immunity activation. A detailed understanding of their pathways contributes to a novel direction for vaccine development.
Topics: Animals; HIV; Hepacivirus; Herpesviridae; Humans; Immunity, Innate; Measles virus; Pathogen-Associated Molecular Pattern Molecules; Respiratory Syncytial Viruses; SARS-CoV-2; Toll-Like Receptors; Viral Proteins; Virus Diseases; Viruses
PubMed: 34375002
DOI: 10.1002/jmv.27265 -
Current Opinion in Virology Apr 2020Measles virus, a member of the genus Morbillivirus, is highly contagious and still shows considerable mortality with over 100000 deaths annually, although efficient... (Review)
Review
Measles virus, a member of the genus Morbillivirus, is highly contagious and still shows considerable mortality with over 100000 deaths annually, although efficient attenuated vaccines exist. Recent studies of measles virus haemagglutinin (MeV-H) and its receptor, including crystallographic and electron microscopic structural analyses combined with functional assays, have revealed how the MeV-H protein recognizes its cognate receptors, SLAM and Nectin-4, and how the glycan shield ensures effective vaccination. In addition, the crystal structure of the MeV-F protein indicated its similarity to those of other paramyxoviruses. Taking into account these data, several models of viral entry/membrane fusion of measles viruses and related paramyxoviruses have been proposed. Furthermore, anti-MeV-F inhibitors targeted to specific regions to inhibit MeV-F protein activation were reported, with potency for preventing MeV infection. The inhibitors targeted for entry events may potentially be applied to treatment of MeV-derived diseases, although escape mutations and drug profiles should be considered.
Topics: Animals; Hemagglutinins, Viral; Humans; Measles; Measles virus; Protein Binding; Receptors, Virus; Virus Internalization
PubMed: 32413678
DOI: 10.1016/j.coviro.2020.04.002 -
Frontiers in Public Health 2020Measles transmissions due to case importations challenge public health systems globally and herd immunities in all countries. In 2019, an imported measles case and its...
Measles transmissions due to case importations challenge public health systems globally and herd immunities in all countries. In 2019, an imported measles case and its subsequently outbreak was found in the Zhoushan Islands. Here, the process of epidemiological investigation and virus tracing were summarized to provide references for the prevention and control of measles in the future. The data on the demographic, epidemiological, and clinical manifestation of measles cases in this outbreak were collected. The 450 bp fragments of the measles virus (MeV) N gene were amplified and sequenced. The genome of the first imported case was further isolated. Then, the maximum-likelihood and time-scaled phylogenetic analysis was conducted. A total of 28 measles cases were confirmed. Their onsets were between March 13 and May 18, 2019. The first patient was from the Ukraine. He was confirmed at the Fever Clinic in Zhoushan hospital on March 15, 2019 and at the same time, another patient had visited the hospital due to another illness and 10 days later, this second case had onset (March 25, 2019). The epidemic curve shows sustained community transmission. The majority of the following cases (19/26) were clustered on the Donggang street which was close to where the second case worked. The 22 measles virus strains successfully isolated from this outbreak all belonged to the D8.2a sub-cluster and clustered with the KY120864/MVs/GirSomnath.IND/42.16/[D8] which was the predominant genotype in the Ukraine during 2018-2019. The analysis of the complete D8 genotype genome pointed to the fact that this prevailing strain originated from India in 2015 and its substitution rate was estimated as 6.91 × 10 (5.64-7.98 × 10) nucleotide substitutions/site/year. This outbreak was caused by an imported case from the Ukraine. There was a possible nosocomial infection between the first case and the second case. Then, the second case played an important role in the spread of virus due to her occupation. The molecular phylogenetic analysis could help to track the origin of the virus. Increasing and maintaining the high level of vaccination coverage (≥95%) and an efficient response to imported cases are essential to prevent and control the recurrence and outbreak of measles virus.
Topics: China; Disease Outbreaks; Female; Humans; India; Islands; Male; Measles; Phylogeny; Ukraine
PubMed: 33335880
DOI: 10.3389/fpubh.2020.600196 -
Deutsche Medizinische Wochenschrift... Jul 2022
Topics: Humans; Measles; Measles virus
PubMed: 35868320
DOI: 10.1055/a-1720-9747 -
Cytokine & Growth Factor Reviews Dec 2020The study of measles virus (MeV) as a cancer immunotherapeutic was prompted by clinical observations of leukemia and lymphoma regressions in patients following measles... (Review)
Review
The study of measles virus (MeV) as a cancer immunotherapeutic was prompted by clinical observations of leukemia and lymphoma regressions in patients following measles virus infection in the 1970s and 1980s. Since then, numerous preclinical studies have confirmed the oncolytic activity of MeV vaccine strains as well as their potential to promote long-lasting tumor-specific immune responses. Early clinical data indicate that some of these effects may translate to the treatment of cancer patients. In this review, we provide a structured summary of current evidence for the anti-tumor immune activity of oncolytic MeV. We start with an overview of MeV oncolysis and MeV-induced immunogenic cell death. Next, we relate findings on MeV-mediated activation of antigen-presenting cells, T cell priming and effector mechanisms to the cancer immunity cycle. We discuss additional factors in the tumor microenvironment which are modulated by MeV treatment as well as the role of anti-viral immunity. Based on these findings, we highlight avenues for rational enhancement of oncolytic MeV immunotherapy by vector engineering. We further point to advantages and drawbacks of experimental models and propose areas warranting promising research. Lastly, we review the available immunomonitoring data from several Phase I clinical trials. While this review presents data for MeV, the concepts and principles introduced herein apply to other oncolytic viruses, providing a framework to assess novel cancer immunotherapies.
Topics: Humans; Immunotherapy; Measles Vaccine; Measles virus; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 32660751
DOI: 10.1016/j.cytogfr.2020.07.009 -
The Lancet. Public Health Aug 2023On Aug 29, 2021, Operation Allies Welcome (OAW) was established to support the resettlement of more than 80 000 Afghan evacuees in the USA. After identification of...
BACKGROUND
On Aug 29, 2021, Operation Allies Welcome (OAW) was established to support the resettlement of more than 80 000 Afghan evacuees in the USA. After identification of measles among evacuees, incoming evacuee flights were temporarily paused, and mass measles vaccination of evacuees aged 6 months or older was introduced domestically and overseas, with a 21-day quarantine period after vaccination. We aimed to evaluate patterns of measles virus transmission during this outbreak and the impact of control measures.
METHODS
We conducted a measles outbreak investigation among Afghan evacuees who were resettled in the USA as part of OAW. Patients with measles were defined as individuals with an acute febrile rash illness between Aug 29, 2021, and Nov 26, 2021, and either laboratory confirmation of infection or epidemiological link to a patient with measles with laboratory confirmation. We analysed the demographics and clinical characteristics of patients with measles and used epidemiological information and whole-genome sequencing to track transmission pathways. A transmission model was used to evaluate the effects of vaccination and other interventions.
FINDINGS
47 people with measles (attack rate: 0·65 per 1000 evacuees) were reported in six US locations housing evacuees in four states. The median age of patients was 1 year (range 0-26); 33 (70%) were younger than 5 years. The age distribution shifted during the outbreak towards infants younger than 12 months. 20 (43%) patients with wild-type measles virus had rash onset after vaccination. No fatalities or community spread were identified, nor further importations after flight resumption. In a non-intervention scenario, transmission models estimated that a median of 5506 cases (IQR 10-5626) could have occurred. Infection clusters based on epidemiological criteria could be delineated into smaller clusters using phylogenetic analyses; however, sequences with few substitution count differences did not always indicate single lines of transmission.
INTERPRETATION
Implementation of control measures limited measles transmission during OAW. Our findings highlight the importance of integration between epidemiological and genetic information in discerning between individual lines of transmission in an elimination setting.
FUNDING
US Centers for Disease Control and Prevention.
Topics: Infant; Humans; Measles virus; Public Health; Phylogeny; Measles; Epidemiologic Studies; Exanthema
PubMed: 37516478
DOI: 10.1016/S2468-2667(23)00130-5 -
Methods in Molecular Biology (Clifton,... 2024Measles IgG avidity assays determine the overall strength of molecular binding between measles-specific IgG antibodies and measles virus antigens. Avidity results can...
Measles IgG avidity assays determine the overall strength of molecular binding between measles-specific IgG antibodies and measles virus antigens. Avidity results can distinguish recent from distant measles virus infections. Individuals who are immunologically naïve to measles virus develop low-avidity antibodies upon measles virus infection or first-time vaccination. Within 4-6 months, antibodies mature to high avidity. Measles avidity assays are most useful in the context of measles elimination. In such settings, avidity and epidemiological and clinical information are used to classify measles breakthrough infections for control and surveillance purposes and to assist in case confirmation when other laboratory results are inconclusive or nonexistent. We present a highly accurate end-titer measles avidity assay that delivers results based on IgG quality (avidity) that are independent of IgG concentration.
Topics: Antibody Affinity; Immunoglobulin G; Humans; Antibodies, Viral; Measles virus; Measles; Antigens, Viral; Enzyme-Linked Immunosorbent Assay
PubMed: 38743375
DOI: 10.1007/978-1-0716-3870-5_18 -
European Journal of Epidemiology Oct 2019Measles vaccination schedules and targets of herd immunity have been designed according to the paradigm that the vaccine is as protective as natural infection, and the... (Review)
Review
Measles vaccination schedules and targets of herd immunity have been designed according to the paradigm that the vaccine is as protective as natural infection, and the virus has remained of a single serotype over many decades. As a result, ongoing measles resurgence is mostly attributed to gaps in immunization. Using official data, we investigated the correlation between the rate of vaccine coverage reported and aggregated at the national level, and the incidence of cases. We discussed the limits of this indicator considered in isolation. We provide a literature overview of measles vaccine efficacy and failures. We questioned whether measles strains could escape the vaccine. Immunization tools and strategies for measles control deserve to be optimized in the current context.
Topics: Disease Outbreaks; Genotype; Humans; Measles; Measles Vaccine; Measles virus; Vaccination
PubMed: 31624970
DOI: 10.1007/s10654-019-00569-4 -
Practical Neurology Apr 2021Subacute sclerosing panencephalitis (SSPE) is a lethal slow viral disease of the central nervous system caused by a defective measles virus. The onset is mostly in...
Subacute sclerosing panencephalitis (SSPE) is a lethal slow viral disease of the central nervous system caused by a defective measles virus. The onset is mostly in childhood, manifesting clinically as decline in academic performance, behavioural changes, motor dysfunction and myoclonus. Adult-onset SSPE is rare and can present as rapidly progressive dementia. We present a young man of Indian origin with adult-onset SSPE with rapidly progressive dementia but no localising neurological signs. The diagnostic clues were parieto-occipital white matter changes on MR brain scan and history of childhood fever with rash. High titres of antimeasles antibody in cerebrospinal fluid confirmed the diagnosis. The long latency from primary measles virus infection to symptom onset can be misleading in adults. SSPE should be considered in adults with dementia, especially in tropical countries where vaccination coverage is suboptimal.
PubMed: 33850035
DOI: 10.1136/practneurol-2020-002880