Introduction to Adenoviruses: From Virus to Medicine

Adenoviruses are nonenveloped particles with a diameter of 70-100 nm, consisting of one linear piece of double-stranded DNA inside an icosahedral capsid. Adenovirus, a DNA virus, was first isolated in the 1950s in adenoid tissue-derived cell cultures, hence the name. Till now, more than 100 serologically distinct types of adenoviruses have been identified, including 49 types that infect humans. Adenoviruses can cause a range of illnesses, including upper respiratory tract infections, lower respiratory tract infections, and symptomatic infections of the gastrointestinal tract or eyes.

Adenovirus infections are widely distributed in human populations, especially in children. Adenovirus infection accounts for up to 20% of childhood pneumonia, primarily in those children younger than 5 years of age. There is no specific treatment for people with adenovirus infection. Adenovirus infection can spread by direct contacts, such as touching or shaking hands with an infected person, by breathing infected air droplets, by touching contaminated surfaces, or by contact with the stool of an infected person.

Currently, there is no adenovirus vaccine available for the general public. It is essential to develop adenovirus related antibodies to detect adenovirus particles or inhibit the propagation of a viral infection, so as to better understand the underlying mechanisms of adenovirus and find possible treatments. However, adenovirus vectors constitute very powerful vehicles for gene transfer with applications in vaccination, cancer treatment, and many monogenic diseases and acquired diseases.  

In the 1950s, exploration and research into the etiology of the common cold led to the discovery of adenovirus. It was not until the 1980s that the therapeutic potential of adenoviruses as gene delivery vectors was discovered. Adenovirus is the first viral gene delivery vector used in humans. More than 60 types of human adenovirus have been found, among which adenovirus serotypes 5 (Ad5) vector is widely used as gene delivery vector. Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens.

The researchers from Umea University, along with teams from Germany, The UK and Hungary, have demonstrated that adenoviruses bind to a specific type of carbohydrate that is overexpressed on certain types of cancer cells. The discovery opens up new opportunities for the development of virus-based cancer treatments. In addition, the FDA approved an adenovirus-based vaccine for the Ebola virus in December 2019. Several adenovirus-based vaccines are currently in clinical and preclinical trials. Vaccines developed against HIV, influenza virus, Mycobacterium tuberculosis, and Plasmodium falciparum are currently under human clinical trials. There are also vaccines under preclinical trials developed against rabies virus, dengue virus, and middle east respiratory syndrome coronavirus. Meanwhile, adenovirus-based vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been authorized for emergency use during the COVID-19 pandemic.

There are several advantages to using adenovirus as a vector or carrier:

※ The genomes of adenovirus are relatively large-sized and well-characterized, making them genetically easy to manipulate;

※ Adenovirus cannot integrate into the host genome, making it a very low risk of insertion mutation;

※ Adenovirus vector has high transduction efficiency and high levels of short-term expression for different quiescent and dividing cell types;

※ Because adenoviruses cause mild infections in humans and their viral replication can be inhibited by genetic modifications, adenovirus-based vaccines are mostly safe and come with very few side effects.