CanSino Biologics Ad5-nCoV Vaccine

With a strong potential that we will see yearly coronavirus outbreaks every winter, we are in desperate need for a vaccine. In my previous post, I discussed the Moderna mRNA vaccine which is currently in Phase I clinical trials. In this post, I will talk about another promising vaccine technology and company also in Phase I clinical trials: CanSino Biologics and their adenovirus-vector vaccine.

Adenovirus-Vector Vaccines

There are three basic types of vaccines: 1. whole pathogen vaccines, 2. subunit vaccines, and 3. nucleic acid vaccines. In whole pathogen vaccines, the virus is killed or significantly weakened and then delivered to a person in order to stimulate an immune response against the virus. In subunit vaccines, only a component of the virus is delivered. Finally in nucleic acid vaccines, the virus DNA or RNA is delivered into a human cell which then get made into viral proteins and prompt an immune response.

An adenovirus-vector vaccine is somewhat like a combination of a whole pathogen vaccine and a subunit vaccine. In this case, we first identify the genetic sequence that codes for proteins on the virus surface. These surface viral proteins will be identified by our immune system and prompt an immune response to kill the virus. The next thing we do is insert this viral genetic sequence into an adenovirus, which are common, relatively benign viruses that cause the common cold, pink eye, etc. The final thing we do is inactivate the E1 gene of the recombined adenovirus, which prevents virus replication and amplification. A schematic of this process is below. A review article detailing the methods and clinical development of adenovirus-vectored vaccines is available from Afkhami et al.

Steps to build an adenovirus-vector vaccine
Source: Afkhami et al. Methods and Clinical Development 2016.

The end result of this process is that we have an inactivated adenovirus that displays a protein of a different virus for which we want to build memory immune cells to fight against (schematic below, more details from Rollier et al.).

Virus antigen presentation to immune cells from adenovirus-vector vaccine
Source: Rollier et al. Current Opinion in Immunology 2011.

The advantages for adenovirus-vector vaccines is that they are safe, create a long-lasting immune response, and create potent T cell responses. One disadvantage is that these vaccine types are less effective if a human has pre-existing immunity to adenoviruses.

CanSino Biologics Technology

CanSino Biologics is a Chinese biopharmaceutical company founded in 2009. To date, they have created 16 vaccine candidates using adenovirus-vector technologies. They have not been in the news as other much as other big biotechnology companies probably because they are based in China, but they have an impressive pipeline of products.

CanSino Biologics Pipeline.
Source: http://www.cansinotech.com/homes/article/plist/45.html

Their most recent vaccine is the Ad5-EBOV vaccine, which is a recombined adenovirus with an Ebola glycoprotein. CanSino Biologics was able to develop this vaccine and get it approved by the Chinese National Government in three years. This vaccine is part of the Chinese National Stockpile emergency use and is part of their national stockpile.

Zhu et al. showed that the Ad5-EBOV vaccine was safe and highly effective in building immune responses against the Ebola glycoprotein in a double-blinded phase II randomized clinical trial.

Ad5-EBOV vaccine creates robust glycoprotein-specific antibody responses.
Source: Zhu et al. Lancet 2016.

CanSino Biologics Ad5-nCoV Vaccine

CanSino Biologics used their same adenovirus-vector pipeline to build a vaccine candidate against COVID-19. In this case, they inserted the spike glycoprotein (the protein responsible for coronavirus entry into cells) into adenoviruses.

The company reported that they were able to trigger a strong response and satisfactory safety profile in preclinical animal studies. They were approved to begin a Phase I clinical trial in China on March 17.

Details of their clinical trial are here. Briefly, they are assessing the safety of three different doses of vaccine, and will measure adverse reactions for up to 6 months. They will also measure the amount of anti-spike protein antibodies, anti-SARS-CoV-2 neutralizing antibodies, and specific T cell responses against the virus for up to 6 months.

Conclusion

CanSino Biologics is another innovative biopharmaceutical company building a much-needed vaccine against coronavirus. They are an established company with many vaccine products and have already brought a vaccine to approval in a short amount of time. I am optimistic that they can succeed in their coronavirus vaccine as well.

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