Adenoviral vector vaccine data are both promising and perplexing

Novel coronavirus SARS-CoV-2 has resulted in a global pandemic with worldwide 6-digit infection rates and thousands of death tolls daily. Enormous efforts are undertaken to achieve high coverage of immunization to reach herd immunity in order to stop the spread of SARS-CoV-2 infection. Several SARS-CoV-2 vaccines based on mRNA, viral vectors, or inactivated SARS-CoV-2 virus have been approved and are being applied worldwide. However, the recent increased numbers of normally very rare types of thromboses associated with thrombocytopenia have been reported, particularly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The statistical prevalence of these side effects seems to correlate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the exact molecular mechanisms are still not clear. The present review summarizes current data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis indicating that coagulopathies, including thromboses, thrombocytopenia, and other related side effects, are correlated to an interplay of the two components in the vaccine, i.e., the spike antigen and the adenoviral vector, with the innate and immune systems, which under certain circumstances can imitate the picture of a limited COVID-19 pathological picture.

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Pitfalls at Chemistry of Adenoviral Vector Vaccine against COVID-19 and How to Circumvent It

Advanced Pharmaceutical Bulletin ◽

10.34172/apb.2022.024 ◽

2021 ◽

Author(s):

Amr Ahmed ◽

Mohammad Nezami ◽

Abdullah Alkattan

Keyword(s):

Adenoviral Vector ◽

Vector Vaccine

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Risk behavior among women enrolled in a randomized controlled efficacy trial of an adenoviral vector vaccine to prevent HIV acquisition

AIDS ◽

10.1097/qad.0b013e328360c83e ◽

2013 ◽

Vol 27 (11) ◽

pp. 1763-1770 ◽

Cited By ~ 12

Author(s):

Richard M. Novak ◽

Barbara Metch ◽

Susan Buchbinder ◽

Robinson Cabello ◽

Yeycy Donastorg ◽

...

Keyword(s):

Risk Behavior ◽

Adenoviral Vector ◽

Efficacy Trial ◽

Vector Vaccine ◽

Randomized Controlled ◽

Hiv Acquisition

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Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic

npj Vaccines ◽

10.1038/s41541-021-00356-x ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Samir Andrade Mendonça ◽

Reka Lorincz ◽

Paul Boucher ◽

David T. Curiel

Keyword(s):

Adenoviral Vector ◽

New Technologies ◽

Rapid Development ◽

Vaccination Campaign ◽

Adenoviral Vectors ◽

Molecular Characteristics ◽

Vector Vaccine ◽

Vector Systems ◽

The Impact ◽

Full Consideration

AbstractAdenoviral vectors have been explored as vaccine agents for a range of infectious diseases, and their ability to induce a potent and balanced immune response made them logical candidates to apply to the COVID-19 pandemic. The unique molecular characteristics of these vectors enabled the rapid development of vaccines with advanced designs capable of overcoming the biological challenges faced by early adenoviral vector systems. These successes and the urgency of the COVID-19 situation have resulted in a flurry of candidate adenoviral vector vaccines for COVID-19 from both academia and industry. These vaccines represent some of the lead candidates currently supported by Operation Warp Speed and other government agencies for rapid translational development. This review details adenoviral vector COVID-19 vaccines currently in human clinical trials and provides an overview of the new technologies employed in their design. As these vaccines have formed a cornerstone of the COVID-19 global vaccination campaign, this review provides a full consideration of the impact and development of this emerging platform.

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The failure to meet GMP on completely eliminating replication-competent adenoviruses in vaccines using the chimpanzees Adv will have disastrous consequences, since it is closest to HAdv species E known to cause respiratory and ocular disease

10.31219/osf.io/cxdq5 ◽

2021 ◽

Author(s):

Sandeep Chakraborty

Keyword(s):

United States ◽

Adenoviral Vector ◽

Respiratory Infections ◽

Respiratory Illness ◽

The United States ◽

Ocular Disease ◽

Lung Damage ◽

Spike Protein ◽

Live Virus ◽

Vector Vaccine

Chimpanzee adenovirus (Y25, Accid:JN254802.1) is being used in the ChAdOx1-nCOV (Covishield) vaccine [1] because it has low human seroprevalence [2].Closest to HAdV4 - respiratory and ocular disease causing speciesThis virus is closest to (95.36% identity, Accid:KX384949.1) to those found in HAdV4 respiratory infections with a ‘concurrent outbreak of coxsackievirus A21 among United States Army Basic Trainees’ [3]. In fact, it was first ‘identified by its association with outbreaks of acute respiratory disease in military recruits’ in the 1950’s [4]. A recent paper noted that ‘increasing infections among civilians are a matter of concern’ [5], including an outbreak of respiratory illness on 5 college campuses in the United States (2018-19) [6]. Also, 15 new HAdV-E4 strains were extracted from cases of respiratory and ocular disease in the US and Japan, indicating the cell specificity of this species [7].What cells will this adenovirus infect?The fiber protein [8] (the spike protein equivalent of the SARS-Cov2 virus) shows very high homology in the N-termimal (Fig. 1). There is no characterization of the human cells this Chimpanzee adenoviral-vector will infect to make Cov2 spike protein - but it surely will be respiratory and ocular cells.Previously, I have raised concern that the replication-deficient adenoviral vector, used to deliver SARS- Cov2 spike protein as a vaccine, could recombine with the homologous human adenoviral to generate a novel adenovirus+spike virus [9].Failure to remove the E1 gene would leave a live virus in the vaccineThe vector vaccine production process (making millions of doses) has known issues, especially the ‘rare appearance of replication-competent adenovirus’ [10], requiring strict GMP-compliance [11]. Brazil has raised similar concerns about the adenovirus-vectored-vaccine from Russia(Sputnik) [12]. This is essentially the E1 replication gene - which is supposed to be absent - but could be picked up from the human cell lines used to manufacture the vaccine doses. The failure to comply with this could lead to disastrous consequences, as these could cause all diseases the live virus could.How to detect - or stop thisMetagenomic studies could easily detect if such an event has occurred, while sequencing or PCR of the vaccine doses for the presence of the E1 gene could stop it from happening. Reports of negative Cov2 PCR with significant lung damage - or new symptoms like conjunctivitis strongly associated with this species of adenoviruses needs to be investigated in more depth

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