Back to Search
Start Over
Live Attenuated Measles Virus Vaccine Expressing Helicobacter pylori Heat Shock Protein A
- Source :
- Molecular Therapy: Oncolytics, Vol 19, Iss, Pp 136-148 (2020)
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Measles virus (MV) Edmonston derivative strains are attractive vector platforms in vaccine development and oncolytic virotherapy. Helicobacter pylori heat shock protein A (HspA) is a bacterial heat shock chaperone with essential function as a Ni-ion scavenging protein. We generated and characterized the immunogenicity of an attenuated MV strain encoding the HspA transgene (MV-HspA). MV-HspA showed faster replication within 48 h of infection with >10-fold higher titers and faster accumulation of the MV proteins. It also demonstrated a superior tumor-killing effect in vitro against a variety of human solid tumor cell lines, including sarcoma, ovarian and breast cancer. Two intraperitoneal (i.p.) doses of 106 50% tissue culture infectious dose (TCID50) MV-HspA significantly improved survival in an ovarian cancer xenograft model: 63.5 days versus 27 days for the control group. The HspA transgene induced a humoral immune response in measles-permissive Ifnarko-CD46Ge transgenic mice. Eight of nine animals developed a long-term anti-HspA antibody response with titers of 1:400 to 1:12,800 without any negative impact on development of protective anti-MV immune memory. MV-HspA triggered an immunogenic cytopathic effect as measured by an HMGB1 assay. The absence of significant elevation of PD-L1 expression indicated that vector-encoded HspA could act as an immunomodulator on the immune check point axis. These data demonstrate that MV-HspA is a potent oncolytic agent and vaccine candidate for clinical translation in cancer treatment and immunoprophylaxis against H. pylori.
- Subjects :
- 0301 basic medicine
Cancer Research
Transgene
lcsh:RC254-282
immune response
Measles virus
03 medical and health sciences
0302 clinical medicine
Immune system
vaccine
Heat shock protein
Pharmacology (medical)
Cytopathic effect
Helicobacter pylori
biology
Immunogenicity
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
biology.organism_classification
Virology
Oncolytic virus
030104 developmental biology
Oncology
heat-shock protein A
Cell culture
measles virus
030220 oncology & carcinogenesis
Molecular Medicine
oncolytic agent
Subjects
Details
- ISSN :
- 23727705
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy - Oncolytics
- Accession number :
- edsair.doi.dedup.....92db905c3acbb0634b626f955e61acab