An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma.

Treating patients who have cancer with vaccines that stimulate a targeted immune response is conceptually appealing, but cancer vaccine trials have not been successful in late-stage patients with treatment-refractory tumours1,2. We are testing melanoma FixVac (BNT111)-an intravenously administered liposomal RNA (RNA-LPX) vaccine, which targets four non-mutated, tumour-associated antigens that are prevalent in melanoma-in an ongoing, first-in-human, dose-escalation phase I trial in patients with advanced melanoma (Lipo-MERIT trial, ClinicalTrials.gov identifier NCT02410733). We report here data from an exploratory interim analysis that show that melanoma FixVac, alone or in combination with blockade of the checkpoint inhibitor PD1, mediates durable objective responses in checkpoint-inhibitor (CPI)-experienced patients with unresectable melanoma. Clinical responses are accompanied by the induction of strong CD4+ and CD8+ T cell immunity against the vaccine antigens. The antigen-specific cytotoxic T-cell responses in some responders reach magnitudes typically reported for adoptive T-cell therapy, and are durable. Our findings indicate that RNA-LPX vaccination is a potent immunotherapy in patients with CPI-experienced melanoma, and suggest the general utility of non-mutant shared tumour antigens as targets for cancer vaccination.

Avian bornaviruses are widely distributed in canary birds (Serinus canaria f. domestica).

Avian bornavirus (ABV) was identified in 2008 as the causative agent of proventricular dilatation disease (PDD) in psittacine birds. In addition, ABV variants were detected in wild waterfowl and in a canary bird. PDD-like diseases were also reported in various other avian species, but it remains unknown whether ABV is involved. In this study we detected ABV in 12 of 30 tested canary bird flocks (40%), indicating a wide distribution of ABV in captive canary birds in Germany. Sequence analysis identified several distinct ABV genotypes which differ markedly from the genotypes present in psittacine birds. Some canaries naturally infected with ABV exhibited gastrointestinal and neurological symptoms which resembled PDD in psittacines, while others did not show signs of disease. Canaries experimentally inoculated with ABV developed infections of the brain and various other organs. The experimentally infected canaries transmitted the virus to sentinel birds kept in the same aviary, but did not show any clinical signs during a five month observation period. Embryonated eggs originating from ABV-infected hens contained ABV-specific RNA, but virus could not be re-isolated from embryonic tissue. These results indicate that ABV is widely distributed in canary birds and due to its association to clinical signs should be considered as a potential pathogen of this species.