Adenoviral Vector DNA- and #SARS-CoV-2 mRNA-Based Covid-19 Vaccines: Possible Integration into the Human #Genome – Are Adenoviral Genes Expressed in Vector-based Vaccines?

This brief review was presented here to facilitate an independent and more balanced discussion on the potential risks due to the presence of adenovirus vector DNA (AstraZeneca, Johnson & Johnson, Sputnik V and others) or SARS-CoV-2 RNA (BioNTech/Pfizer, Moderna) in vaccines that are supposed to protect against Covid-19. Of course, injections of vector-based vaccines into human deltoid muscle is a different matter than rare chance events leading to recombination events between foreign and human DNAs in experimental systems as described above. Moreover, neither type nor frequency of consequences of rare vector integration events can be realistically assessed at present. The recently published results on the benefits of protection against Covid-19 offered by the BioNTech/Pfizer vaccines are encouraging Dagan et al. 2021]. Granted, the jury is still out on whether any of the vaccines’ will protect against the more dangerous new SARS-CoV-2 variants from the UK, South Africa, Brazil and unknown variants that might arise in the future given the poorly controlled levels of viral replication around the world. Lastly, we are ignorant about vaccine protection against the development of prolonged and late-onset symptoms of Covid-19.

The information presented in this review will help future vaccinees to weigh a risk versus benefit assessment, namely the integration events of adenovirus vector or of SARS-CoV-2 RNA reverse transcript DNA at low frequency versus hopefully high vaccine efficacy and protection. Moreover, since SARS-CoV-2 infection by itself can be associated with the integration of reverse transcripts of the viral RNA [Zhang et al, 2020], this series of events might become inescapable in any SARS-CoV-2 infection. Lastly, the extent to which adenoviral gene products might become co-expressed with the SARS-CoV-2 spike glycoprotein upon vector-vaccine injection into human deltoid muscles remains un-investigated. At present we cannot gauge their possible effects on the human organism, if actually expressed. Opportunities and risks, both at the same time, remain beyond our expectations of absolute controls because life and evolution likely have been based on “chance mechanisms” from the very beginning. Clinical observations on long lasting positive RT-PCR test results that imply SARS-CoV-2 DNA integration into the human genome in the course of some Covid-19 cases, render apprehensions about vaccine-associated integration events unrealistic, when compared to the hoped-for benefits by vaccination against Covid-19. The human population of 2021 faces a biomedical crisis of unprecedented dimensions in recent times and will have to accept the best available countermeasures against Covid-19 of the day – Vaccination.

Abstract
Vigorous vaccination programs against SARS-CoV-2-causing Covid-19 are the major chance to fight this dreadful pandemic. The currently administered vaccines depend on adenovirus DNA vectors or on SARS-CoV-2 mRNA that might become reverse transcribed into DNA, however infrequently. In some societies, people have become sensitized against the potential short- or long-term side effects of foreign DNA being injected into humans. In my laboratory, the fate of foreign DNA in mammalian (human) cells and organisms has been investigated for many years. In this review, a summary of the results obtained will be presented. This synopsis has been put in the evolutionary context of retrotransposon insertions into pre-human genomes millions of years ago. In addition, studies on adenovirus vector-based DNA, on the fate of food-ingested DNA as well as the long-term persistence of SARS-CoV-2 RNA/DNA will be described.

Actual integration of viral DNA molecules and of adenovirus vector DNA will likely be chance events whose frequency and epigenetic consequences cannot with certainty be assessed. The review also addresses problems of remaining adenoviral gene expression in adenoviral-based vectors and their role in side effects of vaccines. Eventually, it will come down to weighing the possible risks of genomic insertions of vaccine-associated foreign DNA and unknown levels of vector-carried adenoviral gene expression versus protection against the dangers of Covid-19. A decision in favor of vaccination against life-threatening disease appears prudent.

Informing the public about the complexities of biology will be a reliable guide when having to reach personal decisions about vaccinations.

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