ABSTRACT
The COVID vaccines Janssen and AstraZeneca, based respectively on adenovirus (AdV) serotypes AdV26 and ChAdOx1, have been associated with rare cases of vaccine-induced thrombotic thrombocytopenia (VITT). It was recently demonstrated that the AdVs of the vaccines can bind to the blood protein platelet factor 4 (PF4), an interaction very likely to be involved in VITT. Since there are hundreds of known AdV serotypes, we hypothesized that certain serotypes have a lower affinity for PF4. We therefore aimed to screen a library comprising dozens of serotypes from different AdV species. For this purpose, we established the ELISA-qPCR technology. Like in standard ELISA, AdV viral particles are allowed to specifically interact with PF4 proteins coated on a plate. However, the revelation is not performed by antibody staining, but by qPCR after the genomes of bound AdVs are released through alkaline heat lysis. This technology enables fast, accurate and unbiased assessment of virus molecular interactions. Unlike most tested serotypes, the species D AdV37, AdV69 and AdV70 did not bind to PF4. Even though the ELISA-qPCR technique is not sensitive enough to detect potential low-affinity interactions, these serotypes may avoid or decrease the risk of VITT and represent safer candidates for vaccine or gene therapy vector development. In order to gain deeper insights into the mechanism of virion binding to PF4, we tested how AdV5 affinity for PF4 was affected by genetic removal or PEGylation of different hypervariable regions (HVR) of the hexon protein of the capsid.
ABSTRACT
Efficient therapeutic strategies are needed to counter the COVID-19 pandemic, caused by the SARS-CoV-2 virus. In a context where specific vaccines are not yet available, the containment of the pandemic would be facilitated with efficient prophylaxis. We screened several clinical trials repositories and platforms in search of the prophylactic strategies being investigated against COVID-19 in July 2020. Up to July 5, 2020, only one clinical trial result was published, although we found 112 clinical trial protocols targeting medical workers (n=70, 63%), patients relatives (n=20, 18%) or individuals at risk of severe COVID-19 (n=14, 13%). (Hydroxy)chloroquine was the most frequently evaluated treatment (n=69, 62%), before BCG vaccine (n=12, 11%), this followed by numerous antivirals and immune enhancers. Ninety-eight (88%) clinical trials were randomized with a median of planned inclusions of 530 (IQR 258-1299). Both pre- and post-exposure prophylaxes are investigated.