• Vaccine Name: RIPO(H3.3)
• Target Pathogen: Cancer
• Target Disease: Cancer
• Product Name: PVSRIPO [RIPO(H3.3)]
• Vaccine Ontology ID: VO_0007651
• Type: Recombinant vector vaccine
• Status: Research
• Host Species for Licensed Use: None
• Host Species as Laboratory Animal Model: Mouse
• Antigen: RIPO(H3.3) expresses and processes the foreign H3.3(K27M) antigen, which is a high affinity HLA-A2-restricted tumor neoantigen (Mosaheb et al., 2020).
• Vector:
  • Vector name:
  • VO vector ID: VO_0005434
• Immunization Route: Intramuscular injection (i.m.)
• Description: mRIPO(H3.3) enhances survival in a mouse glioma model (Mosaheb et al., 2020). RIPO(H3.3) also induces type I IFN activation of human DCs (Mosaheb et al., 2020).

Mouse Response

• Vaccination Protocol: Heterozygous hCD155- and AAD(HLA-A2)-tg C57Bl6 mice were obtained by cross breeding hCD155-tg mice with AAD-tg mice. Murine CT2AAAD_H3.3K27M malignant gliomas were implanted intracerebrally in hCD155/AAD-tg mice (Mosaheb et al., 2020). AAD_hCD155 transgenic mice were immunized by i.m. inoculation (day 1), implanted with CT2A_AADH3.3K27M cells for orthotopic tumor initiation (day 7), boosted with the same regimen (day 14), and followed for assessment of weight and neurological status. Mice were euthanized after losing 15% of their max. weight.
• Immune Response: mRIPO(H3.3)-immunized mice survived significantly longer than their mRIPOδ6-immunized littermates. CD8 depletion abrogates the anti-tumor effect of mRIPO(H3.3) immunization (Mosaheb et al., 2020). I.m. immunization with mRIPO(H3.3) significantly extended the survival of CT2A_AADH3.3K27M tumor-bearing mice when compared to mRIPOδ6 immunized mice. In a repeat experiment, mRIPOδ6/mRIPO(H3.3)-immunized animals received intraperitoneal inoculations of anti-CD8 antibodies for CD8 T cell depletion (initiated 7 days prior to tumor implantation). This abolished the therapeutic effect of mRIPO(H3.3) immunization. Thus, PVSRIPO vector-induced H3.3K27M-specific CD8 T cell responses successfully target intracerebral H3.3K27M+ malignant gliomas in vivo (Mosaheb et al., 2020).