« Covid-19: Expert report on vaccines using GMO technologies: summary of Dr Vélot’s note

In September 2020, in support of the procedure for the annulment of the European regulation 2020/1043 which modifies the GMO regulation and allows any clinical trial of GMO drugs intended to treat or prevent Covid-19 to escape prior health and environmental assessments, Dr. C. Vélot published an expert note on the potential health and environmental risks of Covid-19 vaccine candidates, including vaccines using GMO techniques. The interest of the compilation of excerpts presented below is to synthesize for the hurried reader this note by Dr. Vélot, molecular geneticist at the University of Paris-Saclay and President of the Scientific Council of CRRIGEN, the critical reader that we should all be in front of this crucial question being invited to go and read in its entirety this report expressly written for the general public⁽¹⁾.

The types of vaccines that exist:

• live attenuated vaccines:  » the main disadvantages are, on the one hand, the risk of appearance of revertants of the virus (wild strain) by recombination between the vaccine strain and a pathogenic strain present in the vaccinated host (i.e. a re-acquisition of pathogenicity by the initially attenuated vaccine strain), and on the other hand, a contraindication in immunocompromised persons or in pregnant women because of a risk of insufficient attenuation for these persons « .
• inactivated vaccines: the  » approach safer (but not without risk). Their disadvantage is that they provoke a weaker immune response, which requires multiple and repeated injections, as well as the use of adjuvants such as aluminum added to potentiate the immunogenic effect of the vaccine, and likely to cause toxic effects « .
• vaccines using biotechnology

Covid-19 vaccines:

 » Six of them use the inactivated virus, all the others are based on biotechnological approaches and consist in injecting either a) a protein of the virus (antigen); b) Virus-like particles; c) DNA or RNA encoding the antigen.  »

• inactivated vaccines :  » The fact that a vaccine uses an inactivated virus does not mean that there is no risk. The immunizing effect of this type of vaccine is less than with an attenuated virus. It therefore requires repeated injections and the addition of adjuvants, potentially with toxic effects, to potentiate the immunogenic effect. (…) Peveral studies have shown an increased risk of infection (with the same or other viruses) following vaccination with inactivated vaccines. (…) Special care must therefore be taken with inactivated vaccines against covid-19, especially since the virus responsible is completely new and we are far from understanding all its effects.  »

• antigenic protein-containing vaccines and VLP vaccines :  » These vaccines are not very effective and can have toxic effects, mainly due to the adjuvants (such as aluminium or formaldehyde) added to compensate for the low effectiveness and thus to potentiate the stimulation of the immune system, but also possibly to the antigen itself which, by being produced by transgenic cells (which are therefore not those which produce it normally) may have structural or chemical differences that may give it unexpected properties. »
• Vaccines that deliver the RNA or DNA encoding the antigenic protein:
• the risk of appearance of recombinant viruses:  » In a number of cases, these recombinant viruses are much more virulent than the original viruses and can therefore cause aggravated viruses. (…) This is also the risk that is posed to humans when vaccines are generated that deliver viral RNA or DNA into the cells of patients. (…) Vaccination against covid-19, if it becomes a reality, will be a mass vaccination throughout the world. The probability of such events occurring is therefore far from zero, even if it remains probably low in terms of frequency. Such mass vaccination with this type of vaccine could become a large-scale factory of new recombinant viruses. Let’s not forget that it only takes one new virus to appear somewhere in the world for the sanitary, environmental and social consequences to be global and colossal…  »
• the risk of insertionalmutagenesis (= process of appearance of a mutation) (genotoxicity, i.e. which compromises the physical (chromosomal break) or functional integrity of the genome):  » Insertional mutagenesis is a mutation (modification of genetic information) by insertion of a sequence within a genome, this insertion can then inactivate or modify the expression of one or more genes. This risk of genotoxicity for the human cells targeted by the vaccination (whose genome is of course DNA) therefore only concerns vaccines delivering viral DNA, whether the vector is a plasmid or a genetically modified virus. However, this risk may also concern vaccines delivering RNA through a genetically modified RNA viral vector of the type of the AIDS virus (HIV, widely used as a vector) if it has not been properly deprived of its reverse transcriptase and the gene encoding it. Indeed, the viral reverse transcriptase can then convert the delivered RNA into DNA, which will integrate into the genome of the target cells⁽²⁾. Genetically modified viruses are also widely used for gene therapy purposes to deliver the normal version of a human gene that turns out to be defective (mutated) in the treated patient. (…) Several studies have shown the insertional mutagenesis effects caused by different families of RNA viruses (including HIV) [24]. Similarly, several studies in mice have shown that gene delivery by vectors derived from adeno-associated virus (AAV, a small non-pathogenic DNA virus) results in insertional mutagenesis [25]. In 2016, a study on the genotoxic effects of HIV and AAV-derived viral vectors used for gene therapy, concludes that « a thorough knowledge of viral biology and advances in cell genetics are needed to elucidate the nature of viral vector integration site selection and the associated risks. « ⁽³⁾
• risks specifically related to the use of modified viral vectors: immunotoxicity (= immune dysfunction resulting from the exposure of an organism to a xenobiotic. Immune dysfunction can take the form of immunosuppression, allergy or autoimmunity reaction):  » In addition to the risks of recombinant viruses and insertional mutagenesis (especially when the the delivered genetic material is DNA), the viral vectors being themselves immunogenic, they can generate important immunotoxicity effects⁽⁴⁾. In 2002, a pilot gene therapy experiment in 18 boys with a severe metabolic disorder due to a faulty gene on the X chromosome led to the death of an 18-year-old boy due to a fatal systemic inflammatory response caused by the viral vector (disarmed human DNA virus): DNA sequences from the vector were found in most of his tissues. The fact that the 17 other individuals treated did not show this type of response at all shows how difficult this risk is to predict and therefore control. In Belgium, several clinical trials of immunotherapy against cancer using a disarmed virus where more than 15% of its genome has been replaced by two human genes (encoding an antigen present on the surface of cancer cells and an interleukin, a communication protein between immune cells) have shown a non-specific activation of the immune system linked to the vector resulting in an inflammatory reaction and an autoimmune response. Many other studies have shown immunotoxicity effects of various viral vectors used for gene therapy or vaccination. In the case of viral vectors used for vaccination purposes, anti-vector immunity can also directly interfere with the desired vaccine efficacy (vaccine immunogenicity).  »
•  » The use of vaccines that deliver viral genetic material (DNA or RNA) is new or recent. The use of genetically modified viruses as vectors, especially for gene therapy or immunotherapy, has shown how much the undesirable effects are varied, uncontrolled and can be serious. While attempts at immunotherapy are relatively recent, the failures of gene therapy over the past 35 years are a reminder. »
•  » In the case of vaccines, we are in a prevention process. This concerns a considerable number of people, the vast majority of whom are in good health (at least with respect to the disease that the vaccine is supposed to protect us from). Unchecked side effects would therefore have considerable repercussions, especially in a mass vaccination campaign such as the one against covid-19. These consequences could be disastrous from a health point of view, of course, but also from an environmental point of view (in the case, for example, of the propagation of new recombinant viruses). And the fact that it is a preventive approach does not allow for any risk taking.  »
•  » Therefore, these candidate vaccines require a thorough health and environmental assessment that is incompatible with urgency (…) On the contrary, Articles 2 and 3 of the the recent European regulation 2020/1043, according to which any clinical trial of drugs containing or consisting of GMOs and intended to treat or prevent covid-19 escapes prior health and environmental assessments, opens the door to the greatest laxity in terms of evaluation and goes totally against the precautionary principle. In addition, this regulation effectively calls into question the containment legislation that applies to genetically modified microorganisms and viruses. This regulation defines 4 levels of containment (identified from 1 to 4, the containment being more restrictive the higher the number). The handling of pathogenic viruses requires a minimum containment of 2, very often 3 or even 4. The provisions of Regulation 2020/1043 open the door to zero containment even before the health and environmental safety of the genetically modified viruses in question has been proven.  »

Synthesis by Valérie Tilman