![]() Vectors based on human adenovirus types with lower seroprevalence and non-human types including those isolated from chimpanzees have therefore been developed. Pre-existing vector-specific T cells and antibodies may have contributed to the lack of efficacy observed in these studies 2, 3. However, in subsequent human trials including a large Phase IIb HIV vaccine study, some vectors based on HAdV-5 have shown a lack of clinical efficacy 1, 2. The first generation of vectors based on common human serotypes such as human adenovirus type 5 (HAdV-5) elicited potent and protective CD8 + T cell responses in preclinical studies. ![]() Replication defective E1/E3 deleted recombinant adenoviruses have become important tools in the development of new vaccines. Our results suggest that mechanisms governing vector transduction after intramuscular administration in mice may be different from those described in vitro. Remarkably, pseudotyping with the HAdV-5 fiber and/or penton RGD loop had little to no effect on in vivo transgene expression or transgene-specific adaptive immune responses despite considerable species-specific sequence heterogeneity in these components. To investigate the viral factors contributing to these phenotypes, we generated recombinant ChAdOx1 vectors by exchanging components of the viral capsid reported to be principally involved in cell entry with the corresponding sequences from HAdV-5. In this study, superior immunogenicity was associated with markedly higher levels of transgene expression in vivo, particularly within draining lymph nodes. HAdV-5 ( Human adenovirus C) vectors are more immunogenic than chimpanzee adenovirus vectors from species Human adenovirus E (ChAdOx1 and AdC68) in mice, though the mechanisms responsible for these differences in immunogenicity remain poorly understood. However, the potential of a vector to elicit transgene-specific adaptive immune responses is largely dependent on the viral serotype used. Replication defective adenoviruses are promising vectors for the delivery of vaccine antigens.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |