Adenoviral vectors

What a vector is

Adenoviruses are non-enveloped viruses with double-stranded DNA [1]. To turn an adenovirus into a vector, scientists remove the E1 region genes it needs to multiply (often the E3 region too) and insert a gene of interest in their place, for example the gene for a coronavirus protein [1] [2]. After that, the virus cannot make new copies of its genome [1].

Russian developers at the Gamaleya Center describe it this way: non-replicating recombinant adenoviral vectors are an effective molecular tool, and such vectors cannot multiply in ordinary cells [8]. They are grown in a special cell line that itself carries the removed E1 genes [8].

Why adenovirus

• it infects cells of many tissues and makes them actively produce the protein of interest, the antigen [1];
• no significant integration of adenoviruses into the host cell genome has been described [1].

Why type 26 and chimpanzee adenovirus

The best-studied vector is adenovirus type 5. But most people in the world already have immunity to it, and in experiments in mice and monkeys this immunity reduced the effect of vaccination [1] [2].

So developers use rarer types. Vectors based on adenovirus type 26 have proven safe and induce both antibody and cellular immune responses [2]. The ChAdOx1 vector in the AstraZeneca vaccine is made from an adenovirus isolated from chimpanzee feces [1].

Adenoviral vector vaccines

In the Gam-COVID-Vac schedule, the rAd26 vector is given first and rAd5 21 days later; both carry the gene for the full-length coronavirus S protein. In an interim analysis of a phase 3 trial in 21,977 adults, vaccine efficacy was 91.6% [4].

Safety

In 2021, the European Medicines Agency concluded that unusual blood clots with low blood platelets (thrombosis with thrombocytopenia syndrome) should be listed as a very rare side effect of Vaxzevria. At the same time, the agency concluded that the vaccine's benefit in protecting against COVID-19 outweighs the risk [16].

Can you catch adenovirus from the vaccine

No. CDC stresses that a viral vector vaccine cannot cause the disease caused by the virus used as the vector, and it does not change a person's DNA in any way [3]. For example, the adenovirus in Vaxzevria cannot multiply and does not cause disease [13].

Vector vaccines are not designed to protect against adenovirus infection. The vaccine against adenovirus infection itself, a live vaccine against types 4 and 7, is approved only for US military personnel [7]. Learn more in the article on prevention.

Gene therapy

On October 16, 2003, China approved Gendicine, an adenoviral vector carrying the p53 gene for treating head and neck squamous cell carcinoma. It is called the world's first commercial gene therapy [17].

In December 2022, the FDA approved Adstiladrin (nadofaragene firadenovec), a gene therapy based on a non-replicating adenoviral vector [18], for high-grade non-muscle-invasive bladder cancer that does not respond to BCG therapy [19].

The technology also has a tragic chapter. In 1999, 18-year-old Jesse Gelsinger, who had ornithine transcarbamylase deficiency, a genetic disorder, received an adenoviral vector in a clinical trial and died four days later, probably from an immune reaction to the vector [20].