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The efficacy of cancer vaccines has been limited by the immunosuppressive tumor microenvironment, which can be alleviated by immune checkpoint inhibitor (ICI) therapy. Here, we tested if oncolytic viruses (OVs), similar to ICI, can also synergize with cancer vaccines by modulating the tumor microenvironment. VSV‐GP, a chimeric vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus, is a promising new OV candidate. Here, we show that in mouse B16‐OVA melanoma, combination treatment of VSV‐GP with an ovalbumin (OVA) peptide‐loaded dendritic cell (DC) vaccine (DCVacc) significantly enhanced survival over the single agent therapies, although both DCVacc and DCVacc/VSV‐GP treatments induced comparable levels of OVA‐specific CD8 T cell responses. Virus replication was minimal so that direct viral oncolysis in B16‐OVA did not contribute to this synergism. The strong therapeutic effect of the DCVacc/VSV‐GP combination treatment was associated with high numbers of tumor‐infiltrating, highly activated T cells and the relative reduction of regulatory T cells in treated and contra‐lateral nontreated tumors. Accordingly, depletion of CD8 T cells but not natural killer cells abrogated the therapeutic effect of DCVacc/VSV‐GP supporting the crucial role of CD8 T cells. In addition, a drastic increase in several proinflammatory cytokines was observed in VSV‐GP‐treated tumors. Taken together, OVs, similar to ICI, have the potential to markedly increase the efficacy of cancer vaccines by alleviating local immune suppression in the tumor microenvironment., What's new? Cancer vaccine efficacy has been limited by the immunosuppressive tumor microenvironment. By inducing cancer cell death with the release of tumor‐related antigens, oncolytic viruses may have an adjuvant effect. Here, the authors show that a combination of the oncolytic rhabdovirus VSV‐GP and a dendritic cell vaccine is highly effective in the treatment of mouse melanoma, most likely because VSV‐GP reprograms the tumor microenvironment to enhance the effectivity of the vaccine‐induced immune response. Oncolytic viruses have the potential to dramatically increase the efficacy of cancer vaccines by alleviating local immune suppression in the tumor microenvironment.

To investigate prevalence of ongoing activation of inflammation following asymptomatic SARS-CoV-2 infection we characterized immune cell transcriptomes from 43 asymptomatic seropositive and 52 highly exposed seronegative individuals with few underlying health issues following a community superspreading event. Four mildly symptomatic seropositive individuals examined three weeks after infection as positive controls demonstrated immunological activation. Approximately four to six weeks following the event, the two asymptomatic groups showed no significant differences. Two seropositive patients with underlying genetic disease impacting immunological activation were included (Cystic Fibrosis (CF), Nuclear factor-kappa B Essential Modulator (NEMO) deficiency). CF, but not NEMO, associated with significant immune transcriptome differences including some associated with severe SARS-CoV-2 infection (IL1B, IL17A, respective receptors). All subjects remained in their usual state of health from event through five-month follow-up. Here, asymptomatic infection resolved without evidence of prolonged immunological activation. Inclusion of subjects with underlying genetic disease illustrated the pathophysiological importance of context on impact of immunological response.