Adenovirus-Based Vaccines for Fighting Infectious Diseases and Cancer: Progress in the Field

Abstract

The field of adenovirology is undergoing rapid change in response to increasing appreciation of the potential advantages of adenoviruses as the basis for new vaccines and as vectors for gene and cancer therapy. Substantial knowledge and understanding of adenoviruses at a molecular level has made their manipulation for use as vaccines and therapeutics relatively straightforward in comparison with other viral vectors. In this review we summarize the structure and life cycle of the adenovirus and focus on the use of adenovirus-based vectors in vaccines against infectious diseases and cancers. Strategies to overcome the problem of preexisting antiadenovirus immunity, which can hamper the immunogenicity of adenovirus-based vaccines, are discussed. When armed with tumor-associated antigens, replication-deficient and oncolytic adenoviruses can efficiently activate an antitumor immune response. We present concepts on how to use adenoviruses as therapeutic cancer vaccines and consider some of the strategies used to further improve antitumor immune responses. Studies that explore the prospect of adenoviruses as vaccines against infectious diseases and cancer are underway, and here we give an overview of the latest developments.

Endosomophagy clears disrupted early endosomes but not virus particles during virus entry into cells     

“…Recently, Gal3 was reported to be recruited to endosomes disrupted by incoming human adenovirus type 5 (HAdV-C5) [13] [21]. Adenoviruses are non-enveloped human pathogens and widely used vectors in clinical gene therapy and vaccination [22] [23] [24] [25]. HAdV-C2 and C5 enter epithelial cells by receptor-mediated endocytosis and a stepwise uncoating program initiated at the plasma membrane by the differential movements of two receptors, integrin and coxsackievirus adenovirus receptor (CAR) [26] [27] [28].…”

Localization of neutralization epitopes on adenovirus fiber knob from species C

“…Recombinant adenovirus (rAdV) serotype 5 (rAd5)-based vectors are widely utilized for vaccine and gene therapy; however, their efficacy is decreased in both pre-clinical studies and clinical trials by the pre-existing Ad5 immunity (Majhen et al, 2014). Therefore, understanding the functionally relevant determinants of adenovirus (AdV) immunity and developing novel AdV vectors to circumvent Ad5-specific neutralizing antibodies (NAbs) are important goals.…”

The complete genome sequence of human adenovirus 84, a highly recombinant new Human mastadenovirus D type with a unique fiber gene

“…Candidate novel HAdV genotypes are currently evaluated, approved and assigned names by the Human Adenovirus Working Group (hadvwg.gmu.edu) to reduce conflicts and confusion with designation. Human adenoviruses are causative agents of respiratory, gastrointestinal, urinary and ocular diseases, but adenovirus-based vectors are also being developed for cancer treatment, prevention of infectious diseases, and/or to correct genetic disorders (Alonso-Padilla et al, 2016;Baden et al, 2016;Majhen et al, 2014;Zhang and Seto, 2015). As part of our effort seeking to identify new potential vector candidates, we obtained the complete genomic sequence for a respiratory isolate originally identified as a unique intertypic recombinant of species HAdV-D strains.…”