Human adenoviruses (Ads) have long been studied in the basic virology field and are exploited as vectors for gene therapy, vaccination, and oncolytic therapy. Ads are usually mild pathogens, but they can cause severe infections and symptoms in immunocompromised individuals. Ads show a large natural diversity and a broad spectrum of hosts. However, replication-competent and replication-deficient Ad vectors with therapeutic applications have been built mainly starting from human Ad type 5, because generating vectors from other human and animal Ads has proven challenging. This review provides an updated overview of vectors that are not derived from human Ad type 5. We discuss genetic engineering techniques for getting access to the natural diversity of human Ads and for vectorization of alternative Ad types. A catalogue of currently available vectorized human Ads and translational applications thereof is also compiled. We conclude with a perspective on Ad vectorology that looks into the future of Ad vectors in translational medicine.

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Due to the beginning of vaccination against COVID-19, serological discrimination between vaccine-associated humoral response and serology-based surveillance of natural SARS-CoV-2 infections as well as breakthrough infections becomes an issue of relevance. Here, we assessed the differentiated effects of the application of an RNA vaccine using SARS-CoV-2 spike protein epitopes on the results of both anti-spike protein–based serology (EUROIMMUN) and anti-nucleocapsid-based serology (VIROTECH). A total of 80 serum samples from vaccinees acquired at different time points after vaccination was assessed. While positive or borderline serological response in the anti-spike protein assay was observed for all samples (90% both IgG and IgA, 6.3% IgA only, 3.8% borderline IgG only), only a single case of a falsely positive IgM was observed for the anti-nucleocapsid assay as expected due to this assay’s specificity. Positive anti-spike protein antibodies were already detectable in the second week after the first dose of vaccination, with higher titers after the second dose of the vaccine. In conclusion, the combined application of anti-spike protein–based serology and anti-nucleocapsid-based serology will provide a useful option for the discrimination of vaccination response and natural infection.

More than 70 human adenovirus types were identified divided into 7 different species (A-G). Diseases caused by human adenoviruses are type-dependent and can range from mild to severe respiratory infections, gastrointestinal infections or eye infections such as epidemic keratoconjunctivitis. Unfortunately there is no specific anti-adenovirus therapy available. Here we addressed the question whether treatment with cold atmospheric plasma (CAP) for anti-adenoviral therapy such as virus-mediated ulcerations may be feasible. CAP has already been explored for the treatment of dermatological diseases such as chronic wounds. To investigate whether CAP is an effective antiviral tool, purified human adenovirus types derived from different human adenovirus species (HAdV -4, -5, -20, -35, -37, -50) tagged with luciferase were treated with defined dosages of plasma. The CAP treatment was varied by incrementally increasing the time span of CAP treatment. After CAP treatment, the virus containing solution was added to eukaryotic cells and the viral load was determined by measurement of luciferase expression levels. Through the plasma treatment the adenovirus driven luciferase expression directly correlating with adenovirus transduction efficiencies could be reduced for HAdV-5 and HAdV-37. Plasma treatment had no influence on adenovirus derived luciferase expression levels for HAdV-4 and HAdV-50 and it even had a positive effect on luciferase expression levels for HAdV-20 and HAdV-35. These results suggest that CAP has a type dependent effect on adenoviruses and that infectivity can be even increased for certain adenovirus types. Further studies should address the mechanisms behind this phenomenon. In summary we demonstrate that CAP may represent an interesting option for antiviral treatment in a virus type dependent manner.

In previous studies, cold atmospheric plasma (CAP) was explored as an antibacterial and antiviral agent for the treatment of chronic wounds. The aim of the present study was to investigate whether CAP may also be suitable as an antiviral therapy against herpes simplex virus type 1 (HSV-1). HSV-1 most frequently manifests as recurrent herpes labialis, but it can also cause encephalitis, conjunctivitis or herpes neonatorum as a perinatal infection. HSV-1 encoding the reporter gene GFP was propagated. The CAP dose for HSV-1 treatment was gradually increased, ranging from 0–150 s, and aciclovir was used as a positive control. After CAP treatment, the virus suspension was applied to a standard HSV research cell line (Vero cells) and the neuroblastoma cell line SH-SY5Y as a model for neuronal infection. The results showed that plasma treatment had a negligible antiviral effect on HSV-1 in both Vero- and SH-SY5Y cells at high dose. However, when we lowered the viral load 100-fold, we observed a significantly decreased number of internalized HSV-1 genomes 3 h post-infection for CAP-treated viruses. This difference was less pronounced with respect to GFP expression levels 24 h post-infection, which was in sharp contrast to the acyclovir-treated positive control, for which the viral load was reduced from 95 to 25%. In summary, we observed a low but measurable antiviral effect of CAP on HSV-1.