Adenoviruses are considered excellent vectors for delivering target antigens to mammalian hosts because of their capability to induce both innate and adaptive immune responses. Currently, adenovirus-based vaccines are used against a wide variety of pathogens, including Mycobacterium tuberculosis, human immunodeficiency virus (HIV), and Plasmodium falciparum.
What are adenoviruses?
Adenoviruses are non-enveloped, double-stranded DNA viruses (genome size: 34-43 kb; virion size: 70-90 nm), first discovered in the human adenoid tissue in 1953 by Rowe and his colleagues. In humans, adenoviruses generally cause mild respiratory and gastrointestinal tract infections; however, adenovirus-induced infections can be life-threatening in immunocompromised people, or people with pre-existing respiratory or cardiac disorders.
These viruses are isolated from a wide variety of mammalian species, ranging from simians to chimpanzees to human beings. In humans, more than 50 adenovirus serotypes (no cross-neutralization by antibodies) have been identified, which are divided into 7 subgroups (A – G) based on red blood cell agglutination properties and sequence homology.
Adenoviruses express two types of genes: early genes and late genes. Early genes (E1A, E1B, E2, E3, and E4) are necessary for supporting viral replication inside host cells; whereas, late genes are required for host cell lysis, viral assembly, and virion release. Recombinant adenoviruses that are generated in the laboratory as vectors can be either replication-deficient or replication-competent.
Because the E1 gene is essential for viral replication, experimental depletion of the E1 gene generates adenoviruses that are capable of infecting the host cells but cannot grow in numbers because of defective replication. However, some specialized cells, such as HEK 293, can facilitate the replication of E1-deficient adenoviruses by providing E1 functions in trans.
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