Methods and clinical development of adenovirus-vectored vaccines against mucosal pathogens

Abstract

Adenoviruses represent the most widely used viral-vectored platform for vaccine design, showing a great potential in the fight against intracellular infectious diseases to which either there is a lack of effective vaccines or the traditional vaccination strategy is suboptimal. The extensive understanding of the molecular biology of adenoviruses has made the new technologies and reagents available to efficient generation of adenoviral-vectored vaccines for both preclinical and clinical evaluation. The novel adenoviral vectors including nonhuman adenoviral vectors have emerged to be the further improved vectors for vaccine design. In this review, we discuss the latest adenoviral technologies and their utilization in vaccine development. We particularly focus on the application of adenoviral-vectored vaccines in mucosal immunization strategies against mucosal pathogens including Mycobacterium tuberculosis, flu virus, and human immunodeficiency virus.

Figure 1

Organization and function(s) of the adenoviral genome. The organization, orientation, and broad function(s) of the adenoviral transcriptional units are depicted. Knowledge of the entire adenoviral genome is critical in the downstream construction of adenoviral-vectored vaccines.

Figure 2

Development of adenoviral-vectored vaccines through homologous recombination. The most commonly used strategy in the generation of E1-deleted human adenoviral vectors (homologous recombination in a viral packaging cell line) is depicted.

Figure 3

Development of adenoviral-vectored vaccines through a direct-cloning strategy. Generation of adenoviral vectors through direct in vitro molecular cloning of the entire adenovirus is depicted. This represents an alternative strategy in the generation of adenoviral vectors, bypassing the need for homologous recombination.