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Adenovirus serotype Ad19a/64

3rd May 2017

Posted By Paul Boughton


Fig. 1. Ad19a/64 raises levels of common immunisation markers (red circles) beyond immunisation threshold. Application of secondary boost by DNA based vectors, 5 weeks after the prime, increased the effect by a factor 20 (blue squares)

Adenovirus serotype Ad19a/64 is considered by insiders as a promising vaccination and immune oncology tool because it transduces human dendritic cells and myoblasts better than standard adenoviral serotypes.

This novel vector system enables a user to introduce a gene expression of pathogen-derived antigen transiently into these cells.

Expressing an antigen via dendritic cells would, in theory, mean that it is presented to the host’s immune system and should elicit an immune response, effectively vaccinating the host against the targeted pathogen.

Pre-acquired immunities against adenovirus in the human population

While standard adenovirus serotypes perform well in pre-clinical trials, pre-acquired immunities pose a considerate downfall for their later applications.

Ad5 for example, one of the most thoroughly researched serotypes today, would be rejected in a clinical application by up to 15-20% of clients because it is so ubiquitous in many populations around the world.

Ad19a/64 is a much more uncommon serotype and subsequently the prevalence of pre-acquired immunities against Ad19a/64 is much lower in the global population than for most other serotypes.

One question that remained until now, was if an immunity against common Ad serotypes would affect their less common cousins.

Now for the first time, in vivo results from mice, acquired by world-renowned researcher Prof. Peter Holst of the University of Copenhagen, clearly show that Ad19a/64 elicits comparable immune reactions against a given antigen, just as potent as the experimental standard Ad5.

Just as importantly in this context was that Ad19a/64 performed successfully even in animals that were pre-immunised against the common Ad5 serotype.

“The study underlined the importance of Ad19a/64 development into a vaccination vehicle to solve the problem of pre-immunised populations,” commented Sirion Biotech CEO Dr Christian Thirion.

“We already knew that pre-immunisation rates against Ad19a/64 are very low in human populations, an important trait for a future vaccination candidate.” he explained.

“But we were not sure whether pre-acquired immunity against the common Ad5 might generate a cross-reaction. This study seems to have removed that uncertainty,” said Dr Thirion.

 Ad19a/64 as potent prime for even stronger immunisation levels

A second study demonstrates that Ad19a/64 vectors can also act as a powerful prime reagent in a two-step prime-boost vaccination approach, significantly increasing the overall immunisation levels even further.

In this experiment, animals were first treated with antigen-expressing Ad19a/64. As shown in the earlier study the Ad19a/64 vector alone was already enough to elicits a solid increase of IFNg and TNFa positive T-cells in the spleen of the animals, indicating immunisation.

Five weeks after the Ad19a/64-based prime, a secondary boost via DNA vectors was administered. This led to an added increase of marker-positive T-cells by a factor of 20 (Fig. 1).

The synergistic effect of Ad19a/64 combined with a second vector system further fortify its value as a high potential vaccination candidate to treat a number of yet unmet needs.

Further studies by leading scientific groups are currently being conducted, including a vaccination trial in non-human primates and a poc study to establish an immune oncology platform.





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