Special Issue "Recent Advances in Morbillivirus Vaccine Development and Oncolytic Virotherapy"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Antivirals & Vaccines".

Deadline for manuscript submissions: 30 November 2019.

Special Issue Editor

Dr. Liang-Tzung Lin
E-Mail Website
Guest Editor
Taipei Medical University, Department of Microbiology and Immunology, Taipei, Taiwan
Interests: molecular virology; viral entry; antivirals; viral oncolytics

Special Issue Information

Dear Colleagues,

Members of the Morbillivirus genus are enveloped negative-strand RNA viruses that include a number of highly contagious pathogens important to humans and animals. They are known to be transmitted via the respiratory route and cause febrile diseases that can be fatal. Despite the availability of attenuated vaccines against several members, these viruses remain responsible for significant morbidity and mortality in their natural hosts worldwide. The development of molecular biology techniques over the past decades has helped increase the understanding of morbillivirus pathogenesis and explore the possibility to engineer their genomes as viral vectors. Specifically, recent advances have observed the potential use of recombinant morbilliviruses as platforms for novel vaccine development and oncolytic virotherapy against cancers. Continuous research will likely provide further insights into the disease control of morbilliviruses and explore vaccine and therapeutic applications of their genetic vectors.

Dr. Liang-Tzung Lin
Guest Editor

Manuscript Submission Information

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Keywords

  • Morbilliviruses
  • recombinant genome
  • viral vector
  • vaccine development
  • oncolytic virotherapy

Published Papers (3 papers)

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Research

Open AccessArticle
Immunological Effects and Viral Gene Expression Determine the Efficacy of Oncolytic Measles Vaccines Encoding IL-12 or IL-15 Agonists
Viruses 2019, 11(10), 914; https://doi.org/10.3390/v11100914 - 03 Oct 2019
Abstract
Tumor-targeted immunomodulation using oncolytic viral vectors is currently being investigated as a promising strategy in cancer therapy. In a previous study, we showed that a measles virus Schwarz vaccine strain (MeVac) vector encoding an interleukin-12 fusion protein (FmIL-12) is an effective immunotherapy in [...] Read more.
Tumor-targeted immunomodulation using oncolytic viral vectors is currently being investigated as a promising strategy in cancer therapy. In a previous study, we showed that a measles virus Schwarz vaccine strain (MeVac) vector encoding an interleukin-12 fusion protein (FmIL-12) is an effective immunotherapy in the MC38cea murine colon adenocarcinoma model. We hypothesized that MeVac encoding interleukin-15 may mediate enhanced T and NK cell responses and thus increase the therapeutic efficacy, especially in NK cell-controlled tumors. Therefore, we generated MeVac vectors encoding an interleukin-15 superagonist, FmIL-15. Replication and oncolytic capacity, transgene expression, and functionality of MeVac FmIL-15 vectors were validated in vitro. Effects on the tumor immune landscape and therapeutic efficacy of both FmIL-12 and FmIL-15 vectors were studied in the MC38cea and B16hCD46 tumor models. Treatment with MeVac FmIL-15 increased T and NK cell infiltration in both models. However, MeVac FmIL-12 showed more robust viral gene expression and immune activation, resulting in superior anti-tumor efficacy. Based on these results, MeVac encoding a human IL-12 fusion protein was developed for future clinical translation. Full article
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Open AccessArticle
Forced Degradation Studies to Identify Critical Process Parameters for the Purification of Infectious Measles Virus
Viruses 2019, 11(8), 725; https://doi.org/10.3390/v11080725 - 07 Aug 2019
Abstract
Oncolytic measles virus (MV) is a promising treatment for cancer but titers of up to 1011 infectious particles per dose are needed for therapeutic efficacy, which requires an efficient, robust, and scalable production process. MV is highly sensitive to process conditions, and [...] Read more.
Oncolytic measles virus (MV) is a promising treatment for cancer but titers of up to 1011 infectious particles per dose are needed for therapeutic efficacy, which requires an efficient, robust, and scalable production process. MV is highly sensitive to process conditions, and a substantial fraction of the virus is lost during current purification processes. We therefore conducted forced degradation studies under thermal, pH, chemical, and mechanical stress to determine critical process parameters. We found that MV remained stable following up to five freeze–thaw cycles, but was inactivated during short-term incubation (< 2 h) at temperatures exceeding 35 °C. The infectivity of MV declined at pH < 7, but was not influenced by different buffer systems or the ionic strength/osmolality, except high concentrations of CaCl2 and MgSO4. We observed low shear sensitivity (dependent on the flow rate) caused by the use of a peristaltic pump. For tangential flow filtration, the highest recovery of MV was at a shear rate of ~5700 s−1. Our results confirm that the application of forced degradation studies is important to identify critical process parameters for MV purification. This will be helpful during the early stages of process development, ensuring the recovery of high titers of active MV particles after purification. Full article
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Open AccessArticle
Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus
Viruses 2019, 11(7), 614; https://doi.org/10.3390/v11070614 - 05 Jul 2019
Abstract
Starvation sensitizes tumor cells to chemotherapy while protecting normal cells at the same time, a phenomenon defined as differential stress resistance. In this study, we analyzed if starvation would also increase the oncolytic potential of an oncolytic measles vaccine virus (MeV-GFP) while protecting [...] Read more.
Starvation sensitizes tumor cells to chemotherapy while protecting normal cells at the same time, a phenomenon defined as differential stress resistance. In this study, we analyzed if starvation would also increase the oncolytic potential of an oncolytic measles vaccine virus (MeV-GFP) while protecting normal cells against off-target lysis. Human colorectal carcinoma (CRC) cell lines as well as human normal colon cell lines were subjected to various starvation regimes and infected with MeV-GFP. The applied fasting regimes were either short-term (24 h pre-infection) or long-term (24 h pre- plus 96 h post-infection). Cell-killing features of (i) virotherapy, (ii) starvation, as well as (iii) the combination of both were analyzed by cell viability assays and virus growth curves. Remarkably, while long-term low-serum, standard glucose starvation potentiated the efficacy of MeV-mediated cell killing in CRC cells, it was found to be decreased in normal colon cells. Interestingly, viral replication of MeV-GFP in CRC cells was decreased in long-term-starved cells and increased after short-term low-glucose, low-serum starvation. In conclusion, starvation-based virotherapy has the potential to differentially enhance MeV-mediated oncolysis in the context of CRC cancer patients while protecting normal colon cells from unwanted off-target effects. Full article
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