•  Seven Ad26 vectors were designed with variations of the SARS-CoV-2 S protein.

• The most successful and the variant selected for further trials is S.PP which has the "wildtype leader sequence with full-length S with mutation of the furin cleavage site and proline stabilizing mutations." 

Construction of Ad26 vectors

•  Neutralizing antibody responses measured by a pseudovirus neutralization assay and a live virus neutralization assay were measured in the majority of the vaccinated animals with the highest generated by the S.PP vaccine.

•  S-specific IgG and IgA responses were also induced by the Ad26-S.PP vaccine.

•  Further analysis of antibody responses showed  A variety
of Fc effector functions, including antibody-dependent neutrophil
phagocytosis (ADNP), antibody-dependent monocyte cellular phagocytosis (ADCP), antibody-dependent complement deposition (ADCD),
and antibody-dependent NK cell activation (ADNKA), as well as multiple Ig subclasses and FcR binding. 


Ad26 Vaccine Immunogenicity 

•  Animals were infected with 1.0x10^5 TCID50 SARS-CoV-2 through the intranasal and intratracheal paths.

• Animals that were vaccinated with Ad26-S.PP showed no detectable virus in BAL and only one of the animals showed a low amount of virus in NS.

Ad26 Vaccine Protective Efficacy 

•  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.

Bowdoin College

- 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

Viral-Vector Vaccines in Clinical Trial for COVID-19

- Ad26.COV2.S is a vaccine candidate designed by Johnson & Johnson.
- It utilizes a non-replicating adenovirus 26 as a vector expressing the stabilized pre-fusion SARS-CoV-2 spike protein.
- It entered Phase 3 clinical testing in late September, becoming the fourth large-scale vaccine in phase 3 in the United States.

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From our Literary Review:
Johnson & Johnson vaccine candidate is phase 1/2a randomized, double blinded, placebo-controlled clinical study. The purpose of the study was to assess the safety, reactogenicity and immunogenicity of the Ad26.COV2.S. Ad26.COV2.S is a non-replicating adenovirus. The safety and immunogenicity data collected after only a single dose are supportive for further clinical development of Ad26.COV2.S.It is a 26 based vector aiming to express the spike protein of SARS-CoV-2. 


Ad26.COV2.S (Johnson& Johnson) Vaccine Overview

Mercado, N.B., Zahn, R., Wegmann, F. et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature (2020). 
https://doi.org/10.1038/s41586-020-2607-z

Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

- 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

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

- Investigates the Safety and Immunogenicity of the Ad26.COV2.S vaccine in 3 cohorts of people.
- Administered at dose levels of 5x10^10 or 1x10^11 either as single dose or two doses spaced by 56 days.
- Measured S specific antibodies by ELISA, neutralizing titers by wtVNA and CD4+ Th1 and Th2 and CD8+ immune responses by ICS.
- Concluded that the safety profile and immunogenicity after one dose at the lower dosage were sufficient as a potentially protective vaccine and therefore moved to phase 3 testing. 

- Methods
- Results 
- Discussion

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