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Cytokine & Growth Factor Reviews Dec 2020Cancer immunotherapy using tumor-selective, oncolytic viruses is an emerging therapeutic option for solid and hematologic malignancies. A considerable variety of viruses... (Review)
Review
Cancer immunotherapy using tumor-selective, oncolytic viruses is an emerging therapeutic option for solid and hematologic malignancies. A considerable variety of viruses ranging from small picornaviruses to large poxviruses are currently being investigated as potential candidates. In the early days of virotherapy, non-engineered wild-type or vaccine-strain viruses were employed. However, these viruses often did not fully satisfy the major criteria of safety and efficacy. Since the advent of reverse genetics systems for manipulating various classes of viruses, the field has shifted to developing genetically engineered viruses with an improved therapeutic index. In this review, we will summarize the concepts and strategies of multi-level genetic engineering of oncolytic measles virus, a prime candidate for cancer immunovirotherapy. Furthermore, we will provide a brief overview of measles virus-based multimodal combination therapies for improved tumor control and clinical efficacy.
Topics: Humans; Immunotherapy; Measles virus; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 32718830
DOI: 10.1016/j.cytogfr.2020.07.005 -
Vaccine Feb 2022Measles is endemic in Africa; measles mortality is highest among infants. Infant measles antibody titer at birth is related to maternal immune status. Older mothers are...
Measles is endemic in Africa; measles mortality is highest among infants. Infant measles antibody titer at birth is related to maternal immune status. Older mothers are likelier to have had measles infection, which provides higher antibody titers than vaccine-induced immunity. We investigated the relationship between maternal age and measles susceptibility in mother-infant pairs in Mali through six months of infancy. We measured serum measles antibodies in 340 mother-infant pairs by plaque reduction neutralization test (PRNT) and calculated the proportion of mothers with protective titers (>120 mIU/mL) at delivery and the proportion of infants with protective titers at birth, and at three and six months of age. We explored associations between maternal age and measles antibodies in mothers and infants at the timepoints noted. Ten percent of Malian newborns were susceptible to measles; by six months nearly all were. Maternal and infant antibody titers were highly correlated. At delivery, 11% of mothers and 10% of newborns were susceptible to measles. By three and six months, infant susceptibility increased to 72% and 98%, respectively. Infants born to younger mothers were most susceptible at birth and three months. Time to susceptibility was 6.6 weeks in infants born to mothers with measles titer >120-<430 mIU/mL versus 15.4 weeks when mothers had titers ≥430 mIU/mL. Maternal and newborn seroprotective status were positively correlated. Improved strategies are needed to protect susceptible infants from measles infection and death. Increasing measles immunization coverage in vaccine eligible populations, including nonimmune reproductive-aged women and older children should be considered.
Topics: Adolescent; Adult; Antibodies, Viral; Child; Female; Humans; Immunity, Maternally-Acquired; Infant; Infant, Newborn; Mali; Measles; Measles Vaccine; Measles virus
PubMed: 35101263
DOI: 10.1016/j.vaccine.2022.01.012 -
Current Opinion in Virology Apr 2020Measles virus causes a disease with seemingly innocent symptoms, such as fever and rash. However, measles immune suppression causes increased susceptibility to... (Review)
Review
Measles virus causes a disease with seemingly innocent symptoms, such as fever and rash. However, measles immune suppression causes increased susceptibility to opportunistic infections that are responsible for the majority of over 100000 yearly fatalities. The pathogenesis of measles is complex, because measles virus uses multiple receptors to infect different cell types in different phases of the disease. Experimental morbillivirus infections with wild-type viruses in natural host species have demonstrated that direct infection and depletion of memory immune cells causes immune amnesia. This was confirmed in studies of a measles outbreak in unvaccinated children and provides an explanation for epidemiological observations of long-term increases in morbidity and mortality after measles.
Topics: Animals; Disease Models, Animal; Humans; Immunologic Memory; Measles; Measles virus
PubMed: 32339942
DOI: 10.1016/j.coviro.2020.03.002 -
Mayo Clinic Proceedings Sep 2019Recent measles epidemics in US and European cities where vaccination coverage has declined are providing a harsh reminder for the need to maintain protective levels of... (Review)
Review
Recent measles epidemics in US and European cities where vaccination coverage has declined are providing a harsh reminder for the need to maintain protective levels of immunity across the entire population. Vaccine uptake rates have been declining in large part because of public misinformation regarding a possible association between measles vaccination and autism for which there is no scientific basis. The purpose of this article is to address a new misinformed antivaccination argument-that measles immunity is undesirable because measles virus is protective against cancer. Having worked for many years to develop engineered measles viruses as anticancer therapies, we have concluded (1) that measles is not protective against cancer and (2) that its potential utility as a cancer therapy will be enhanced, not diminished, by prior vaccination.
Topics: Child; Child, Preschool; Communicable Disease Control; Communication; Europe; Female; Humans; Male; Measles; Measles virus; Oncolytic Virotherapy; Prevalence; Risk Assessment; United States; Vaccination
PubMed: 31235278
DOI: 10.1016/j.mayocp.2019.05.006 -
International Journal of Molecular... Dec 2022Self-replicating RNA viruses have become attractive delivery vehicles for therapeutic applications. They are easy to handle, can be rapidly produced in large quantities,... (Review)
Review
Self-replicating RNA viruses have become attractive delivery vehicles for therapeutic applications. They are easy to handle, can be rapidly produced in large quantities, and can be delivered as recombinant viral particles, naked or nanoparticle-encapsulated RNA, or plasmid DNA-based vectors. The self-replication of RNA in infected host cells provides the means for generating much higher transgene expression levels and the possibility to apply substantially reduced amounts of RNA to achieve similar expression levels or immune responses compared to conventional synthetic mRNA. Alphaviruses and flaviviruses, possessing a single-stranded RNA genome of positive polarity, as well as measles viruses and rhabdoviruses with a negative-stranded RNA genome, have frequently been utilized for therapeutic applications. Both naturally and engineered oncolytic self-replicating RNA viruses providing specific replication in tumor cells have been evaluated for cancer therapy. Therapeutic efficacy has been demonstrated in animal models. Furthermore, the safe application of oncolytic viruses has been confirmed in clinical trials. Multiple myeloma patients treated with an oncolytic measles virus (MV-NIS) resulted in increased T-cell responses against the measles virus and several tumor-associated antigen responses and complete remission in one patient. Furthermore, MV-CEA administration to patients with ovarian cancer resulted in a stable disease and more than doubled the median overall survival.
Topics: Humans; Animals; Female; Oncolytic Viruses; RNA; RNA Viruses; Ovarian Neoplasms; Measles virus; Oncolytic Virotherapy; Neoplasms
PubMed: 36555262
DOI: 10.3390/ijms232415622 -
The Journal of Infection Sep 2021We attempted to establish a molecular investigation by Next Generation sequencing of the measles virus (MeV) strains circulating in Marseille-France during the last...
OBJECTIVES
We attempted to establish a molecular investigation by Next Generation sequencing of the measles virus (MeV) strains circulating in Marseille-France during the last outbreak that occurred between 2017 and 2019.
METHODS
The circulating MeV were isolated from clinical samples using cell culture method and whole genomes were sequenced by Illumina Miseq Next Generation. Genotyping and comparative analyses were assessed by phylogenetic reconstructions. Clinical and epidemiological data from cases were also recorded.
RESULTS
A total of 110 MeV strains were isolated in cell culture. Our analysis based on whole genome sequences of 98 isolates confirmed that 93 strains belonged to the genotype D8 and 5 to the genotype B3. Phylogenetic analyses revealed 4 distinct MeV circulating clones in Marseille. Measles mostly occured in children < 5 years-old and in adults 30-50 years-old. Measles infection also occurred in 2 adequately vaccinated cases (2 doses). Among 63 measles cases of whom we had available clinical data informations, a total of 35 patients were hospitalized and 19 developed complications including one death case recorded.
CONCLUSIONS
Whole Genome Sequencing seems to be a useful tool for more refined genomic characterization of large measles outbreak. Vaccination strategies for measles eradication need to be re-evaluated in the current context.
Topics: Adult; Child, Preschool; Disease Outbreaks; France; Genotype; Humans; Measles; Measles virus; Middle Aged; Phylogeny
PubMed: 34310945
DOI: 10.1016/j.jinf.2021.07.011 -
Cureus Aug 2020Otosclerosis is a common cause of conductive hearing loss which is an autoimmune inflammatory disorder related to abnormal bone remodeling of the human otic capsule that... (Review)
Review
Otosclerosis is a common cause of conductive hearing loss which is an autoimmune inflammatory disorder related to abnormal bone remodeling of the human otic capsule that has complex etiopathogenesis attributed to genetics, autoimmunity, viral infection, inflammation, hormonal factor, environmental factor, and disturbed bone metabolism. It has a prevalence of 0.3%-0.4% in Caucasians, which makes up 5-9% of all hearing loss and 18-22% of all conductive hearing loss. This review article aims to study the postulated role of sustained measles virus infection in the etiopathogenesis of otosclerosis, among others. A PubMed search of the related topic identified 97,990 articles. After we applied the inclusion and exclusion criteria, it was determined that 52 articles were relevant, which included 38 observational studies, 13 review articles, and a systematic review. Among them, 33 observational studies, 13 review articles and a systematic review spotted a positive association between persistent measles virus infection and otosclerosis. On the contrary, five observational studies reported no evidence of the association. The majority of the current literature supported the presence of the measles virus component in the otosclerotic stapes samples and its role in the etiopathogenesis of otosclerosis. Measles virus infection may have the amplitude to initiate a pathological process, which in the presence of other factors like autoimmunity and genes plays a significant role in causing otosclerosis. However, other studies have failed to show the presence of the measles virus component in otosclerotic stapes. So, more studies are needed to probe the role of persistent measles virus infection in the etiopathogenesis of otosclerosis.
PubMed: 32968571
DOI: 10.7759/cureus.9908 -
Pathogens (Basel, Switzerland) Apr 2021An interesting Perspective article recently published in the offers an insightful overview on the benefits provided by the mass vaccination of children against Severe...
An interesting Perspective article recently published in the offers an insightful overview on the benefits provided by the mass vaccination of children against Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), the betacoronavirus responsible for the dramatic CoronaVirus Disease-2019 (COVID-19) pandemic [...].
PubMed: 33918683
DOI: 10.3390/pathogens10040449 -
Travel Medicine and Infectious Disease 2021While measles vaccination is widely implemented in national immunisation programmes, measles incidence rates are increasing worldwide. Dutch inhabitants who were born...
BACKGROUND
While measles vaccination is widely implemented in national immunisation programmes, measles incidence rates are increasing worldwide. Dutch inhabitants who were born between 1965-1975 may have fallen between two stools, lacking protection from a natural infection, and having missed the introduction of the measles vaccination schedule. With this study we aim to find the measles seroprevalence in travellers born between 1965 and 1975, compared to those born before 1965 and after 1975.
METHODS
Families travelling to Eastern Europe or outside Europe during the preceding year were recruited via Dutch secondary schools between 2016 and 2018. Their vaccination status was assessed using questionnaires, vaccination records and measles serology in dried blood spot (DBS) eluates. Measles virus antibody concentrations were determined with an ELISA (EUROIMMUNE®) and a subset was retested with a focus reduction neutralization assay (FRNT).
RESULTS
In 188 (79%) of the 239 available DBS eluates, the ELISA could detect sufficient measles virus-specific IgG antibodies. Of the negative samples that were retested with FRNT, 85% remained negative, resulting in an overall seroprevalence of 82% [95% CI 76-86]. Children had a lower seroprevalence (72%) than adults (87%). Travellers born between 1965 and 1975 were protected in 89%.
CONCLUSIONS
In this study, we report a measles seroprevalence of 82% among Dutch travelling families. Remarkably, seroprevalence rates were lowest in children (12-18 years) instead of travellers born between 1965 and 1975. Although a fraction of people without detectable antibodies may be protected by other immune mechanisms, these data suggest that measles (re)vaccination should be considered for travellers to endemic regions.
Topics: Adult; Antibodies, Viral; Child; Humans; Immunization Schedule; Measles; Measles Vaccine; Seroepidemiologic Studies; Vaccination
PubMed: 34728385
DOI: 10.1016/j.tmaid.2021.102194 -
Current Opinion in Virology Apr 2020The measles virus replication complex represents a potentially important, but as yet relatively unexplored target for viral inhibition. Little is known about the... (Review)
Review
The measles virus replication complex represents a potentially important, but as yet relatively unexplored target for viral inhibition. Little is known about the molecular mechanisms that underpin replication and transcription in paramyxoviruses. In recent years it has become clear that conformational dynamics play an important role in paramyxoviral replication, and that a complete understanding of the viral cycle requires a description of the structural plasticity of the different components. Here, we review recent progress in this direction, covering the dynamics of the nucleocapsid assembly process, high resolution structure and dynamics of protein:RNA interactions, and the investigation of the role of intrinsic conformational disorder in pre-assembly nucleoprotein/phosphoprotein complexes. Finally, we discuss the role of viral factories in the form of phase-separated membraneless organelles formed by measles virus phospho and nucleoproteins that promote the assembly of nucleocapsid structures.
Topics: Animals; Humans; Measles; Measles virus; Nucleocapsid; Nucleoproteins; RNA, Viral; Virus Replication
PubMed: 32570195
DOI: 10.1016/j.coviro.2020.05.006