Replication-defective adenovirus vectors require a high dose, approximately 10 billion virus particles per dose, because the virus cannot reproduce itself.

“replication defective means that the virus has been genetically engineered so it can't reproduce itself but it has also been genetically engineered so it contains the gene that codes for the coronavirus spike protein so that when you're inoculated with that vaccine the cell takes up that particle which does not amplify itself it enters the nucleus it then is transcribed it's transcribed to messenger rna the messenger rna is translated to a protein and that protein is excreted so it's good news bad news the good news is it's replication defective therefore it can't cause disease because the virus is reproducing itself the bad news is it's replication effective meaning you have to give a lot of virus to get enough of those virus particles into the cell to make the protein you're interested in about 10 billion virus particles per dose”