- ChAdOx1  are a desirable platform of vaccine because they are immunogenic in older adults and can be manufactured at large scale
- Vaccines made by combining adenoviral vectors, DNA, and poxviral vectors have been used in an attempt to improve immunogenicity--Emergence of antivector immunity inhibits the potency of a second dose, so homologous adenoviral regimens are typically avoided
- "The ChAdOx1 nCoV-19 vaccine (AZD1222) consists of the replication-deficient simian adenovirus vector ChAdOx1, containing the full-length structural surface glycoprotein (spike protein) of SARS-CoV-2, with a tissue plasminogen activator leader sequence. ChAdOx1 nCoV-19 expresses a codon-optimised coding sequence for the spike  protein (GenBank accession number MN908947)."

ChAdOx1 nCoV-19 vaccine by The University of Oxford

These two vaccine candidates are non-replicating viral vector vaccine (along with Ad5-nCoV and ChAdOx1 vaccine candidates). 

Approach 1: 
- "modified dendritic cells expressing SARS-CoV-2 minigenes"
- in Phase I/II

Approach 2: 
- artificial antigen-presenting cells expressing SARS-CoV-2 minigenes
- Phase I

NCT04276896/NCT04299724 COVID-19 vaccine by Shenzhen Geno-Immune Medical Institute

•  The vaccine uses adenovirus serotype 26 as a vector encoding a prefusion stabilized SARS-CoV-2-spike immunogen, a protein which mediates entry of the SARS-CoV-2 into host cells. 

•  A single immunization induced a neutralizing antibody response and complete protection against SARS-CoV-2 in 5 out of 6 rhesus macaques.

•  The phase 1/2a clinical trial is now underway in Belgium and the United States with phase 3 starting in September if results are positive.

Ad26- vectored COVID-19 vaccine by Johnson & Johnson Creation/ Animal Testing

- Contains replication-defective Ad5 vectors expressing the full-length spike gene (S) based on Wuhan-Hu-1 (YP_009724390)
- Phase 2 Trials show vaccine dosage at 5 x 10^10 viral particles is safe and effective in inducing significant immune responses after a single immunization. 
- Completed phase 2 trials and planning on phase 3

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From our Literary Review:

Adenoviral vectors, armed with forgien genetic material, are already widely used in vaccines and cancer treatments (Zhang & Zhou, 2016). Ad5-nCoV, or Cansino, is a vaccine for COVID-19 that was developed in China by CanSino Biologics. Cansino was one of the first coronavirus vaccines to be tested in humans, beginning March of 202 and ending May of the same year. April 11, 2020 was the start of a randomized, double blind, placebo controlled phase II clinical trial. The middle and low doses tested exhibited a significant neutralizing antibody response with seroconversion of neutralizing antibodies of 59% and 47% respectively and seroconversion of binding antibody of 96% and 97% respectively. At 28 days post vaccination 95% of the middle and 91% of the low dosage groups showed cellular or humoral immune responses.
Ad5-nCoV uses replication defective mutant adenovirus type 5 as a viral vector to express the SARS-CoV-2 spike protein, the main antigen component responsible for entry into the cell. The purpose of this structure is to have the common cold virus mimic coronavirus. 

Adenovirus based viral vector technology appears to be a preferred strategy for prevention of newer infectious diseases. Adenovirus vector based vaccine candidates for prevention of infectious disease are being tested more often in order to protect humans from infectious diseases. It has been seen to be one of the most effective vectors to deliver antigens to the host cells of mammals. In addition, it can also induce strong innate and adaptive immune responses, is easily manipulated, and has a reduced risk for insertional mutagenesis of the viral gene. Ultimately, Ad vectored vaccines have shown great potential as candidates in infectious disease prevention.


Ad5-nCov vectored COVID-19 Vaccine by CanSino Biologics

- Using Ad5 by CanSino Biologics
- Using Chimpanzee adenovirus  (ChAdOx1 nCoV-19) by The University of Oxford
- Using Ad26 by Johnson & Johnson
- Using NCT04276896/NCT04299724 by Shenzhen Geno-Immune Medical Institute

Carnegie Mellon University

Smith College

Viral-Vector vaccines genetically engineer another virus, referred to as vectors, to carry genetic materials from the coronavirus and produce coronavirus proteins in the human body. These vectors are weakened and does not cause disease. Two main types are (shown in image):

Viral-Vector Vaccines for COVID-19

Callaway, E. (2020). The race for coronavirus vaccines: A graphical guide. Nature, 580(7805), 576-577. doi:10.1038/d41586-020-01221-y

https://www.nature.com/articles/d41586-020-01221-y

The race for coronavirus vaccines: a graphical guide

Shin, M.D., Shukla, S., Chung, Y.H. et al. COVID-19 vaccine development and a potential nanomaterial path forward. Nat. Nanotechnol. 15, 646–655 (2020). doi: 10.1038/s41565-020-0737-y

https://doi.org/10.1038/s41565-020-0737-y

COVID-19 vaccine development and a potential
nanomaterial path forward

Viral-Vector Vaccines in Clinical Trial for COVID-19

Information gained from studies done on both the immune response and vaccine development to related betacoronaviruses can help us gain insight on the immunopathology of SARS-CoV-2 and guide the devlopment of a vaccine. 

Vaccine Development for SARS-CoV-2 Based on Knowledge Gained from SARS-CoV and MERS-CoV

- A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2

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