Live Attenuated Measles Virus Vaccine Expressing Helicobacter pylori Heat Shock Protein A

Ianko D. Iankov, Cheyne Kurokawa, Kimberly Viker, Steven I. Robinson, Arun Ammayappan, Eleni Panagioti, Mark J. Federspiel, Evanthia Galanis

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)136-148
Number of pages13
JournalMolecular Therapy - Oncolytics
Volume19
DOIs
StatePublished - Dec 16 2020

Keywords

  • Helicobacter pylori
  • heat-shock protein A
  • immune check point
  • immune response
  • measles virus
  • oncolytic agent
  • vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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