High-Affinity DARPin Allows Targeting of MeV to Glioblastoma Multiforme in Combination with Protease Targeting without Loss of Potency.

Measles virus (MeV) is naturally cytolytic by extensive cell-to-cell fusion. Vaccine-derived MeV is toxic for cancer cells and is clinically tested as oncolytic virus. To combine the potential of MeV with enhanced safety, different targeting strategies have been described.

Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model.

Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to occur, making it one of the WHO´s targets for accelerated vaccine development. One vaccine candidate is based on live-attenuated measles virus (MV) vaccine encoding the MERS-CoV spike glycoprotein (MERS-S). MV-MERS-S(H) induces robust humoral and cellular immunity against MERS-S mediating protection.

Antigen-specific oncolytic MV-based tumor vaccines through presentation of selected tumor-associated antigens on infected cells or virus-like particles.

Recombinant vaccine strain-derived measles virus (MV) is clinically tested both as vaccine platform to protect against other pathogens and as oncolytic virus for tumor treatment. To investigate the potential synergism in anti-tumoral efficacy of oncolytic and vaccine properties, we chose Ovalbumin and an ideal tumor antigen, claudin-6, for pre-clinical proof of concept. To enhance immunogenicity, both antigens were presented by retroviral virus-like particle produced in situ during MV-infection.

A single amino acid substitution in the measles virus F₂ protein reciprocally modulates membrane fusion activity in pathogenic and oncolytic strains.

Differences in fusion activity between measles virus (MV) attenuated, oncolytic strain MV(NSe) and pathogenic MV(wt323) are reflected in amino acid 94 of the fusion (F) proteins. A valine 94 in F(NSe) (naturally) or F(wt323) (introduced) correlated with enhanced cell-cell fusion activity during transient glycoprotein expression or recombinant MV infections irrespective of the strains' targeted receptors, whereas the reverse effect was found for methionine 94. Enhanced fusogenicity was determined by weaker glycoprotein interaction and correlated positively with cytotoxicity in both virus strains.